As cholesterol levels are lowered the death rate increases

Analysis of six trials show that as cholesterol levels are lowered the death rate increases

This study was published in the British Medical Journal 1990 Aug 11;301(6747):309-14

Study title and authors:

Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.

Muldoon MF, Manuck SB, Matthews KA.

Department of Medicine, University of Pittsburgh, PA 15260.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/2144195

This study analysed the findings of six cholesterol reduction trials. The participants in the six cholesterol reduction trials received either diet based, drug based, a mixture of diet and drug cholesterol lowering treatment or placebo. The trials lasted for an average of 4.8 years and included 24,847 male participants who were followed for a total of 119,000 person years. The average age of the men was 47.5 years.

The analysis found:
(a) The men receiving cholesterol reduction treatment reduced their cholesterol levels by about 10%.
(b) The men receiving cholesterol reduction treatment had a 7% increase in death rates compared to the men taking a placebo.

The results of this analysis of six trials show that as cholesterol levels are lowered the death rate increases.

===============================================================

Read the complete article here.

Facts do not need clarification. - Kendrick

     

Proving that black is white

  

Last week I was going through some old files, and presentations, in a vague effort to clean up my computer. Whilst looking a one of many thousands of studies I had filed away I came across this paper: ‘Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons¹.’

I read it, and immediately recalled why I kept it. For it came to the following, final, conclusion:

 ‘Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults.’

I remember when I first read this paper a few years ago. My initial thought was to doubt that it could be true. Most of the evidence I had seen strongly suggested that, in the elderly, a high cholesterol level was actually protective against Coronary Heart Disease (CHD).

However, when a bunch of investigators state unequivocally that elevated cholesterol is a risk factor for heart disease, I try to give them the benefit of the doubt. So I read the damned thing. Always a potentially dangerous waste of precious brainpower.

Now, I am not going to dissect all the data in detail here, but one sentence that jumped out of the paper was the following:

‘Persons (Over 65) with the lowest total cholesterol levels ≤4.15 mmol/L had the highest rate of death from coronary heart disease, whereas those with elevated total cholesterol levels ≥ or = 6.20 mmol/L seemed to have a lower risk for death from coronary heart disease. ‘

Now, I can hardly blame you if you struggled to fit those two quotes together. On one hand, the conclusion of the paper was that .. ‘Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults.’ On the other hand, the authors reported that those with the lowest total cholesterol levels had the highest rate of CHD; whilst those with the highest cholesterol levels had the lowest rate of CHD.

Taken at face value, this paper seems to be contradicting itself…. utterly. However, the key word here, as you may have already noted, is seemed. As in… those with elevated total cholesterol levels ≥ or = 6.20 mmol/L seemed to have a lower risk for death from coronary heart disease. ‘

Now you may think that this is a strange word to use in a scientific paper. Surely those with elevated total cholesterol levels either did, or did not, have a lower risk of death from CHD? Dying is not really something you can fake, and once a cause of death has been recorded it cannot be changed at a later date. So how can someone seem to die of something – yet not die of it?

The answer is that you take the bare statistics, then you stretch them and bend them until you get the answer you want. Firstly, you adjust your figures for established risk factors for coronary heart disease – which may be justified (or may not be). Then you adjust for markers of poor health – which most certainly is not justified – as you have no idea if you are looking at cause, effect, or association.
Then, when this doesn’t provide the answer you want, you exclude a whole bunch of deaths, for reasons that are complete nonsense. I quote:

‘After adjustment for established risk factors for coronary heart disease and markers of poor health and exclusion of 44 deaths from coronary heart disease that occurred within the first year, (my bold text) elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased.’

Why did they exclude 44 deaths within the first year?  Well, they decided that having a low cholesterol levels was a marker for poor health, and so it was the poor health that killed them within the first year.

The reason why they believed they could do this is that, a number of years ago, a man called Iribarren decreed that the raised mortality always seen in those with low cholesterol levels is because people with low cholesterol have underlying diseases. And it is these underlying diseases that kill them. (What, even dying from CHD. And how, exactly does CHD cause a low cholesterol levels….one might ask).

In truth, there has never been a scrap of evidence to support Iribarren’s made-up ad-hoc hypothesis. [A bottle of champagne for anyone who can find any evidence]. However, it is now so widely believed to be true, that no-one questions it.

Anyway, without chasing down too many completely made-up ad-hoc hypotheses, the bottom line is that this paper stands a perfect example of how you can take a result you don’t like and turn it through one hundred and eighty degrees. At which point you have a conclusion that you do like.

Young researcher: (Bright and innocent)  ‘Look, this is really interesting, elderly people with low cholesterol levels are at greater risk of dying of heart disease.’

Professor: (Smoothly threatening) ‘I think you will find…. if you were to look more carefully, that this is not what you actually found….. Is it? By the way, how is your latest grant application going?’

Young researcher: (Flushing red at realising his blunder) ‘Yes, by golly, how silly of me. I think I really found that elderly people with high cholesterol levels are at a greater risk of dying of heart disease.’

Professor: ‘Yes, excellent. Be a good lad, find a good statistician to make sure the figures make sense, and write it up.’

For those who wonder at my almost absolute cynicism with regard to the current state of Evidence Based Medicine, I offer this paper as a further example of the way that facts are beaten into submission until they fit with current medical scientific dogma.

As a final sign off I would advise that any paper that has the word ‘clarifying’ in its title, should be treated with the utmost suspicion. I think George Orwell would know exactly what the word clarifying means in this context. Facts do not need clarification.

1: Corti MC et al: Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Ann Intern Med. 1997 May 15;126(10):753-60
========================================================================================================
Read the complete article here.

Statin = substantial increase in diabetes risk in postmenopausal women

Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative

ABSTRACT

Background  This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women participating in the Women's Health Initiative (WHI).

Methods  The WHI recruited 161 808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 with ongoing follow-up. The current analysis includes data through 2005. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. Cox proportional hazards models were used to estimate the risk of DM by statin use, with adjustments for propensity score and other potential confounding factors. Subgroup analyses by race/ethnicity, obesity status, and age group were conducted to uncover effect modification.

Results  This investigation included 153 840 women without DM and no missing data at baseline. At baseline, 7.04% reported taking statin medication. There were 10 242 incident cases of self-reported DM over 1 004 466 person-years of follow-up. Statin use at baseline was associated with an increased risk of DM (hazard ratio [HR], 1.71; 95% CI, 1.61-1.83). This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications. Subset analyses evaluating the association of self-reported DM with longitudinal measures of statin use in 125 575 women confirmed these findings.

Conclusions  Statin medication use in postmenopausal women is associated with an increased risk for DM. This may be a medication class effect. Further study by statin type and dose may reveal varying risk levels for new-onset DM in this population.
 

• 

Figures in this Article

Given the success of statins in both primary and secondary prevention of cardiovascular morbidity and mortality,^1- 6 their use is progressively increasing, especially among older Americans.⁷ With such widespread use, even small risks are apparent alongside benefits. One emerging risk is an increased incidence of diabetes mellitus (DM). There is evidence that incident DM associated with statin use may be more common in the elderly, in women, and in Asians.^8- 12 A recent analysis suggests that preexisting metabolic risk factors control incident DM rate with statin medication.¹³ It is unclear if this risk varies with individual statins or if this is a dose-driven class effect.^9,14 Although experimental and clinical studies find that individual statins act differently on glucose homeostasis as a function of relative lipophilicity and/or potency of action,¹⁵ other findings differ. A recent meta-analysis of 17 randomized controlled trials by Mills et al¹⁶ found a class effect increase of new-onset DM with statins (odds ratio [OR], 1.09; 95% CI, 1.02-1.16) similar to that reported by Sattar et al.⁹ Possibly, the grouping of statins masks the effect variation of individual statins. Still, at some given dose threshold, differences may be overcome, as implied by a meta-analysis of 5 trials comparing intensive to moderate dosing regimens using mainly atorvastatin and simvastatin.^13,17 Notably, meta-analysis results display intertrial and intratrial variability in diagnostic and statistical methods and do not consistently consider confounding factors. Moreover, contributing sample sizes do not permit balanced comparison by statin type, sex, race/ethnicity, and age. Similarly, single studies may uncover only part of a greater topography.

 

As a large part of the aging population, postmenopausal women have not been fully represented in past clinical trials.¹⁶ Sex differences in DM pathogenesis are well recognized.^18- 19 Using the Women's Health Initiative (WHI) data, we evaluated the overall effect of statin medication use on incident DM risk and examined these associations by specific statin agent. We stratified analyses by race/ethnicity, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) category, and age group to determine if any associations were modified by these factors. In addition, we conducted subgroup analysis in women with and without self-reported cardiovascular disease (CVD) at baseline to address potential confounding and selection bias.

METHODS

PARTICIPANTS

The WHI recruited 161 808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 and followed consenting participants. Of these women, 68 132 were enrolled in 1, 2, or all 3 of the clinical trial (CT) arms: the Dietary Modification Trial, the Hormone Trial, and the Calcium and Vitamin D Trial. Another 93 676 women were enrolled into a prospective observational study (OS).^20- 23 The WHI eligibility criteria included the ability to complete study visits with expected survival and local residency for at least 3 years. Original exclusion criteria addressed conditions that would limit full participation in the study. This analysis used WHI data through 2005. After exclusion for prevalent DM, missing data, and use of cerivastatin (this medication was withdrawn from the market in 2001 for safety reasons), a total of 153 840 women were included (Figure).

 

Figure. Flowchart for statin users and diabetes mellitus (DM) analyses using data sets from the Women's Health Initiative.                    

+

 

MEASUREMENT AND CLASSIFICATION OF STATIN MEDICATIONS

The current medication regimens of all CT participants were inventoried at baseline and at years 1, 3, 6, and 9. In the OS, medication data were inventoried at baseline and year 3. At each inventory, the brand or generic name on the medication label was matched to the corresponding item in the Master Drug Data Base (Medi-Span, Indianapolis, Indiana). We sorted for statin use as users or nonusers at baseline and year 3. Given that Sattar et al⁹ found a null effect of lipophilicity among statins, and in the absence of dose information, we determined statin categories by relative potency of action to decrease low-density lipoprotein cholesterol. Accordingly, statins were designated as low (fluvastatin, lovastatin, pravastatin) or high (simvastatin, atorvastatin) potency.^24- 25

IDENTIFICATION OF DM

At baseline and at each semiannual (CT) or annual (OS) contact, incident treated DM was identified by questionnaire and was defined as a self-report of a new physician diagnosis of treated DM. This method of identification of prevalent and incident DM has been used in prior publications by the WHI investigators.^18,26- 28 The accuracy of self-reported DM in the WHI trials has been assessed using medication and laboratory data, and self-reported DM was found to be reliable.²⁹

COVARIATES

Baseline questionnaires ascertained demographic and health history information, including race/ethnicity, age, educational attainment, family history of DM, family history of depression, self-report of CVD, hormone therapy use, and smoking status. Baseline self-report for CVD has been previously validated in the WHI^30- 31 and found to have reasonable agreement with hospital discharge International Classification of Diseases, Ninth Revision (ICD-9) codes.

 

The metabolic equivalents of physical activities and average daily nutrient intake were computed, using detailed methods described elsewhere.^32- 33 Trained and certified clinic staff measured height using a fixed stadiometer and weight by a calibrated balance-beam scale. Relative weight as BMI was calculated from these values. Blood was analyzed for glucose and insulin for the random 6% WHI-CT blood subsample at baseline, year 1, year 3, year 6, and year 9. Fasting glucose was analyzed using the hexokinase method with interassay coefficients of variation less than 2%.²⁶ Insulin was measured by enzyme-linked immunosorbent assay. The WHI used the homeostasis model assessment of insulin resistance (HOMA-IR), which was developed for application in large epidemiologic investigations as an alternative to the glucose clamp. HOMA-IR = fasting plasma insulin (μIU/mL) × fasting plasma glucose (mmol/L)/22.5.³⁴

STATISTICAL ANALYSIS

Cox proportional hazards (PH) models were used to estimate hazard ratios (HRs) of DM by statin medication use. The dependent variable was time to occurrence of DM determined by self-report (ie, time to event). The time to event was calculated as the interval between enrollment date and the earliest of the following: (1) date of annual medical history update when new DM was ascertained (observed outcome) and (2) date of the last annual medical update during which DM status was ascertained (censored outcome). The primary independent variable in these analyses was statin use at baseline, coded as a binary variable. We present 3 Cox PH models to examine the association between baseline statin use and DM: model 1 estimates the unadjusted HRs (and associated 95% CIs) of the effects of statin use on incident DM; model 2 presents age- and race/ethnicity–adjusted HRs; and model 3 presents HRs adjusted for all potential confounding variables at baseline (age, race/ethnicity, education, cigarette smoking, BMI, physical activity, alcohol intake, energy intake, family history of DM, hormone therapy use, study arm, and self-report of CVD). Similar analyses were conducted for specific type of statin medication use at baseline, categorized as low vs high potency.

 

Since individuals using statins may have different underlying conditions that could put them at elevated risk for DM, we conducted several subgroup analyses to control confounding by indication. First, we conducted subgroup analyses by age, race/ethnicity, and BMI categories to examine whether the associations of statin use and onset of DM differed by categories of these variables. Age was categorized into 3 groups (50-59 years, 60-69 years, and ≥70 years). Race/ethnicity was assessed according to 4 major groups (white, African American, Hispanic, Asian). Body mass index was categorized into 3 groups (<25 .0="" 25.0-29.9="" 2="" analyses="" analysis="" at="" baseline.="" conducted="" cvd="" either="" finally="" in="" of="" or="" propensity="" score="" second="" self-reported="" similar="" subgroups="" sup="" we="" with="" without="" women="">35

was performed to reduce the confounding effects of other factors in the evaluation of the association between statin use and DM risk within an observational study setting. Participant-specific propensity scores were estimated from a logistic regression model to predict the probability of statin prescription. Covariates considered for inclusion into the logistic regression model included age, BMI, self-report of hypertension, self-report of CVD, family history of DM, smoking status, and physical activity. The final propensity score model retained all covariates noted herein with the exception of physical activity, which was an insignificant predictor of statin use. The association between statin use and DM risk was evaluated in Cox PH models after adjusting for the estimated propensity score.

 

After exclusion for cases of DM before year 3 (146 women), use of cerivastatin (651 women), and missing medication data at year 3 (2 women), our longitudinal analyses were conducted in a subset of 125 575 women from the OS and the CT arm at baseline and year 3 visits. Statin use was sorted into 4 categories: (1) never took statin; (2) use at both baseline and at the year 3 visit, (3) use only at baseline; and (4) use only at the year 3 visit. The HRs for DM by statin use were estimated similarly based on Cox PH models.

RESULTS

 PARTICIPANTS’ CHARACTERISTICS

Participant characteristics are listed in Table 1. At baseline, the mean (SD) age of women included in our sample was 63.2 (7.3) years. Approximately 16.30% of the women were from racial/ethnic groups other than white, of which the largest representation was African American (8.32%). Only 2.56% (3922 women) were Asian. At baseline, 7.04% of participants took statin medication. Of these, 30.29% took simvastatin; 27.29%, lovastatin; 22.52%, pravastatin; 12.15%, fluvastatin; and 7.74%, atorvastatin. Comparison between statin users and nonusers showed significant differences in baseline characteristics.

 

Table Graphic Jump Location Table 1. Characteristics of 153 840 Study Participants, Women's Health Initiative^a

+

 

STATIN USE AT BASELINE AND DM INCIDENCE

A total of 10 242 incident cases of DM were reported over 1 004 466 person-years of follow-up. Table 2 presents results regarding the association between statin use at baseline and risk of incident DM. In unadjusted models, statin use at baseline was significantly associated with an increased DM risk (HR, 1.71; 95% CI, 1.61-1.83) when compared with nonuse. This association was decreased but remained significant after adjusting for potential confounders (HR, 1.48; 95% CI, 1.38-1.59). This association was observed for all types of statin. Similar risk associations were found in use of either high- or low-potency statins, with multivariate-adjusted HRs of 1.45 (95% CI, 1.36-1.61) and 1.48 (95% CI, 1.36-1.61) compared with nonusers, respectively. Table 3 shows subgroup analyses by race/ethnicity, BMI category, and age group. In both unadjusted and adjusted models, statin use was consistently associated with increased risk of DM across subgroups by age. We observed significantly increased risk of DM by statin use within subgroups of white, Hispanic, and Asian women in both unadjusted and adjusted models. In adjusted models, we observed HRs of 1.49 (95% CI, 1.38-1.62), 1.18 (95% CI, 0.96-1.45), 1.57 (95% CI, 1.14-2.17), and 1.78 (95% CI, 1.32-2.40) among whites, African Americans, Hispanics, and Asians, respectively. Statin use was also associated with a significantly increased risk of DM within 3 subgroups according to BMI (<25 .0="" 1.09-1.33="" 1.20="" 1.48-1.87="" 1.57-2.29="" 1.66="" 1.89="" 25.0-29.9="" 25.0="" 29.9="" 30.0="" a="" adjusted="" adjusting="" after="" all="" among="" and="" associated="" bmi="" ci="" compared="" confounders.="" dm="" for="" groups="" higher="" hrs="" in="" increased="" less="" lower="" models="" moreover="" observed="" of="" or="" p="" potential="" respectively.="" risk="" significantly="" statin="" than="" the="" to="" use="" was="" were="" when="" with="" within="" women="">

 

Table Graphic Jump Location Table 2. Association Between Diabetes Mellitus (DM) Risk and Statin Use Status at Baseline in 153840 Participants

+

 

Table Graphic Jump Location Table 3. Association Between Diabetes Mellitus (DM) Risk and Statin Use Status at Baseline, Within Age, Race/Ethnicity, and BMI Subgroups in 153840 Participants                    

+

 

STATIN USE AT BASELINE AND RISK OF DM AMONG POSTMENOPAUSAL WOMEN WITH AND WITHOUT HISTORY OF CVD

 

To address potential confounding and selection bias, we conducted subgroup analyses among postmenopausal women with and without a history of CVD (Table 4). Among a subset of 24 842 women who self-reported CVD at baseline, we found that statin use was associated with an increased risk of DM (HR, 1.52; 95% CI, 1.36-1.71). These associations remained significant after adjusting for potential confounders (HR, 1.46; 95% CI, 1.29-1.65). Similar findings were observed among women without CVD at baseline.

 

Table Graphic Jump Location Table 4. Risk of Diabetes Mellitus (DM) by Statin Use Among Women With and Without Medical History of Cardiovascular Disease (CVD) at Baseline                    

+

 

PROPENSITY SCORE ANALYSES

In unadjusted models, statin use was significantly related to DM risk (HR, 1.71; 95% CI, 1.61-1.83). When the propensity score was included, the estimated HR attenuated to 1.38 (95% CI, 1.29-1.47). On inclusion of other confounders in the model, the HR was essentially unaltered (HR, 1.40; 95% CI, 1.31-1.51). Propensity score adjusted models yielded HRs of 1.38 (95% CI, 1.23-1.54) and 1.40 (95% CI, 1.29-1.53) for respective increased risk with either high- or low-potency statin use at baseline compared with nonuse.

LONGITUDINAL MEASURES OF STATIN USE AND RISK OF DM

When compared with those who never received statin therapy, unadjusted HRs of 1.82 (95% CI, 1.65-2.00), 1.75 (95% CI, 1.43-2.14), and 1.81 (95% CI, 1.67-1.97) were observed for the groups of women who reported statin use at both baseline and at the year 3 visit, reported statin use only at baseline, and reported statin use only at the year 3 visit, respectively (Table 5). The risk associations remained significant after adjusting for age, race/ethnicity, other potential confounders, and propensity score. The multivariate adjusted HRs were 1.47 (95% CI, 1.32-1.64), 1.44 (95% CI, 1.15-1.80), and 1.60 (95% CI, 1.47-1.75), respectively.

 

Table Graphic Jump Location Table 5. Risk of Diabetes Mellitus (DM) by Statin Use at Baseline and 3-Year Follow-up in 125575 Participants

+

 

SENSITIVITY ANALYSIS

A sensitivity analysis was conducted on a subset of 3706 women without DM at baseline and enrolled in the WHI CT for whom fasting glucose measurements were available at baseline and at least 1 additional follow-up visit. Diabetes mellitus was identified based on fasting glucose levels of 126 mg/dL (6.99 mmol/L) or higher. In unadjusted models, statin use at baseline was not significantly related to DM risk (HR, 1.06; 95% CI, 0.61-1.86). However, using baseline through year 6 data in the CT arm, we found that the statin users had higher fasting glucose levels and HOMA-IR compared with non–statin users, with increasing values from baseline to year 6 follow-up.

==================================================================
Read the complete article here.

Effect Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction - JAMA

Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction:  The TACT Randomized Trial                 

ABSTRACT 

 

 

Importance  Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.

Objective  To determine if an EDTA-based chelation regimen reduces cardiovascular events.

Design, Setting, and Participants  Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial.

Interventions  Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events.

Main Outcome Measures  The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036.

Results  Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), but the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]).

Sensitivity analyses examining the effect of patient dropout and treatment adherence did not alter the results.

Conclusions and Relevance  Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures. These results provide evidence to guide further research but are not sufficient to support the routine use of chelation therapy for treatment of patients who have had an MI.
==================================================================
Read the complete article here.

 

Antibiotics and Statins: A Deadly Combo? - Laino

Antibiotics and Statins: A Deadly Combo?

By Charlene Laino, Senior Writer, Gupta Guide

Published: June 19, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

For best viewing, click the bottom right corner for full screen.

Action Points

• Prescribing clarithromycin or erythromycin to older patients taking the most commonly prescribed statins raised the risk for statin toxicity.
• Point out that to decrease the risk of statin toxicity for a patient who requires a mycin antibiotic, the study authors suggested that azithromycin is the best option.

Prescribing clarithromycin or erythromycin to older patients taking the most commonly prescribed statins, which are metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4), raised the risk for statin toxicity, according to a population-based retrospective cohort study.

Clarithromycin and erythromycin, but not azithromycin, inhibit cytochrome CYP3A4, and that inhibition increases blood concentrations of statins that are metabolized by CYP3A4 to potentially dangerous levels, Amit M. Patel, MD, of the London Health Sciences Center in Ontario, and colleagues reported online in the Annals of Internal Medicine.

Compared with azithromycin, co-prescription of atorvastatin, simvastatin, or lovastatin with clarithromycin or erythromycin was associated with a 0.02% increase in the absolute risk of hospitalization with rhabdomyolysis within 30 days (95% CI 0.01%-0.03%). That translates to a relative risk increase of 2.17 (95% CI, 1.04-4.53).
Risks were also increased for:

• Acute kidney injury -- absolute risk increase, 1.26% (95% CI 0.58%-1.95%); RR 1.78 (95% CI 1.49-2.14)
• All-cause mortality -- absolute risk increase, 0.25% (95% CI 0.17%-0.33%); RR 1.56 (95% CI 1.36-1.80)

"Statins are the No. 1 class of drugs prescribed in North America," co-author Amit Garg, MD, PhD, also from the London Health Sciences Center, said in a statement.

Coprescription of a statin with a macrolide antibiotic is very common. Until now, the clinical and population-based consequences of this potential drug-drug interaction were unknown, he said.
While the absolute risk increase is relatively small, "given the frequency at which statins are prescribed and the high rate of coprescription seen in our study and in other jurisdictions, this preventable drug-drug interaction remains clinically important. The results suggest many deaths and hospitalizations due to acute kidney injury in Ontario may have been attributable to this interaction, the researchers wrote.

For the study, the researchers examined the frequency of statin toxicity in continuous statin users older than 65 years who were prescribed clarithromycin (n=72,591) or erythromycin (n=3,267), compared with azithromycin (n=68,478) in Ontario from 2003 to 2010.

The primary outcome was rhabdomyolysis within 30 days of the antibiotic prescription.
The most commonly prescribed statin was atorvastatin (73%), followed by simvastatin (24%) and lovastatin (3%).

American Heart Association spokesperson Robert Eckel, MD, of the University of Colorado at Denver, said that although the potential for drug-drug interactions between certain antibiotics and statins was known, this study really underscores the potential for dangerous, even fatal complications.
"And while the study was only done in elderly patients, this "provides a signal" these complications could develop in younger people as well," he told "The Gupta Guide."

There's another option too, said John Higgins, MD, of the University of Texas Health Science Center at Houston. "If you have a patient on a statin and you need a mycin antibiotic, the study suggests you choose azithromycin.

"But there is also a statin that is not metabolized by the CYP3A4 system -- pravastatin. So you really have two choices here. Switch the antibiotic or switch the statin," he said.

The study has several major strengths, including its large size, Eckel said
But there are limitations, too, Higgins said. "For example they only studied people over 65, with a median age of 74, who may have a lot of comorbidities. So these patients may be more prone to some of these problems anyway," he said.

Additionally, it is an observational study and therefore subject to all the biases of such an analyses -- that is, they show associations, but cannot prove casual relationships, he said.
Finally, "coders record the health problems and we know that coders often don't note complications in all patients," Higgins said. "So, if anything, the risks may have been higher than those found in the study," he said.

Also, the researchers themselves noted that despite the large sample size, they could "not meaningfully examine interactions with each CYP3A4-metabolized statin individually. However, given the known effect on CYP3A4 statin pharmacokinetics, it remains prudent to generalize the coprescription warning to atorvastatin, simvastatin, or lovastatin with clarithromycin or erythromycin," they wrote.

Said Patel, "The results provide important safety information regarding these commonly prescribed medications. When prescribing clarithromycin or erythromycin to patients on these statins, preventive measures should be considered, such as cessation of the statin for the duration of the antibiotic therapy, increased monitoring for adverse events, or use of a different antibiotic that does not interact with these statins."

The authors also suggested that clinicians take advantage of free online drug interaction programs and/or software aimed at improving the overall safety of polypharmacy in older adults.
And there's always the obvious solution: Better multidisciplinary collaboration between departments, Eckel added.

Do you double-check what statins your patients are on before prescribing an antibiotic? Add Your Knowledge below. -- Sanjay Gupta, MD.

The investigators received grant support from the Academic Medical Organization of Southwestern Ontario to conduct this research. This project was conducted at the Institute for Clinical Evaluative Sciences site at Western University. The Institute for Clinical Evaluative Sciences is funded by an annual grant from the Ontario Ministry of Health and Long-term Care. The Institute for Clinical Evaluative Sciences site at Western University is funded by an operating grant from the Academic Medical Organization of Southwestern Ontario. Dr. Garg was supported by a Canadian Institutes of Health Research Clinician Scientific Award.
Eckel and Higgins have no financial conclicts of interest to disclose.

Primary source: Annals of Internal Medicine
Source reference:Patel AM, et al "Statin toxicity from macrolide antibiotic coprescription" Ann Intern Med 2013; DOI: 10.7326/0003-4819-158-12-201306180-00004.
======================================================================
Read the complete article here.

Will 2015 Dietary Guidelines Advisory Committee address Dr. Rimm’s legitimate concerns? - Watson

Why was a respected Harvard researcher afraid he would get “kicked off the stage”?

Alan Watson | May 10, 2012 

 

On October 31, 2008, during that first meeting of the 2010 Dietary Guidelines Advisory Committee (DGAC), Dr. Eric B. Rimm, Associate Professor of Medicine, Harvard Medical School, questioned what he called the “artificial limit” on dietary fat in the U.S. Dietary Guidelines.

 

From the transcripts:  www.cnpp.usda.gov/DGAs2010-Meeting1.htm

 

Dr. Rimm: “I wanted to make a radical point, one for which I’ll probably get kicked off the stage, but the whole issue of total fat and the 20 to 35 percent of calories from fat is one that has troubled me…”

Dr. Rimm:  “… But the high end, 35 percent of calories from fat, actually was not really based on much science; it’s based on the fact that we don’t have a lot of science beyond 35 percent, and there was a concern that higher fat diets would lead to obesity.”

Dr. Rimm:  I think if you look at the science, there is actually no good human data to suggest that higher fat diets lead to obesity. If anything, higher fat diets, at 35 to 40 percent, lead to lower triglycerides because it’s a lower carbohydrate intake.

Dr. Rimm:  “… I think there is the dogma that low-fat diets are beneficial, and you can go in the grocery store and see a lot of low-fat foods that are essentially just high in carbohydrate, highly processed sugars.”

Dr. Rimm did not get “kicked off the stage,” but the issue never came up again. He was simply ignored. The final report of the 2010 Dietary Guidelines ultimately contained even more stringent reductions in saturated fats – recommending that most Americans reduce saturated fat intake to just 7 percent of calories.

In an interview with Melissa Healy in the Los Angeles Times, June 28, 2010, Dr. Walter C. Willett, Chairman, Department of Nutrition, Harvard School of Public Health, agreed with his Harvard associate:

“The best available evidence demonstrates that percent of calories from fat in a diet has no bearing on weight loss – a point the dietary guidelines committee acknowledges.”

 

“It makes no sense to base the dietary guidelines on an outdated recommendation.”

 

Why did the Committee table Dr. Rimm’s concerns about artificial limits on dietary fat? Why was a respected Harvard researcher afraid he would get “kicked off the stage”? Are Committee members not allowed to question “low fat equals good health”? If so, why has USDA and HHS convened a 2015 Dietary Guidelines Advisory Committee?

New evidence exonerating saturated fats as a cause of heart disease continues to accumulate:

Dr. Ronald Krause – a highly respected American Diet Heart researcher – reviewed 21 studies involving 350,000 subjects to assess the correlation between saturated fat consumption and cardiovascular disease. The conclusion:

Intake of saturated fat was not associated with an increased risk of heart disease or stroke (American Journal of Clinical Nutrition, Jan. 13, 2010).

 

A prospective study from Australia looked at adults over a period of 15 years and found that people who ate the most full-fat dairy products had a 69 percent lower risk of cardiovascular death than those who ate the least (European Journal of Clinical Nutrition, April 7, 2010).
The Japan Collaborative Cohort Study for Evaluation of Cancer Risk found that saturated fat intake was inversely associated with mortality from stroke (American Journal of Clinical Nutrition, Aug. 4, 2010).

Researchers at Louisiana State University found that eating eggs for breakfast resulted in greater weight loss and better energy levels than eating two bagels even though the number of calories was about the same (The FASEB Journal 2007; 21:538.1).

Will the 2015 Dietary Guidelines Advisory Committee address Dr. Rimm’s legitimate concerns?
==================================================================
Read the complete article here.

Are statins and omega-3s incompatible? - Davis

Are statins and omega-3s incompatible?
Posted on June 18, 2013 by Dr. Davis

French researcher, Dr. Michel de Lorgeril, has been in the forefront of thinking and research into nutritional issues, including the Mediterranean Diet, the French Paradox, and the role of fat intake in cardiovascular health. In a recent review entitled Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?, he explores the question of whether statin drugs are, in effect, incompatible with omega-3 fatty acids.

Dr. Lorgeril makes several arguments:

1) Earlier studies, such as GISSI-Prevenzione, demonstrated reduction in cardiovascular events with omega-3 fatty acid supplementation, consistent with the biological and physiological benefits observed in animals, experimental preparations, and epidemiologic observations in free-living populations.

 2) More recent studies (and meta-analyses) examining the effects of omega-3 fatty acids have failed to demonstrate cardiovascular benefit showing, at most, non-significant trends towards benefit.

He points out that the more recent studies were conducted post-GISSI and after agencies like the American Heart Association’s advised people to consume more fish, which prompted broad increases in omega-3 intake. The populations studied therefore had increased intake of omega-3 fatty acids at the start of the studies, verified by higher levels of omega-3 RBC levels in participants.

In addition, he raises the provocative idea that the benefits of omega-3 fatty acids appear to be confined to those not taking statin agents, as suggested, for instance, in the Alpha Omega Trial. He speculates that the potential for statins to ablate the benefits of omega-3s (and vice versa) might be based on several phenomena:

 –Statins increase arachidonic acid content of cell membranes, a potentially inflammatory omega-6 fatty acid that competes with omega-3 fatty acids. (Insulin provocation and greater linoleic acid/omega-6 oils do likewise.)

–Statins induce impaired mitochondrial function, while omega-3s improve mitochondrial function. (Impaired mitochondrial function is evidenced, for instance, by reduced coenzyme Q10 levels, with partial relief from muscle weakness and discomfort by supplementing coenzyme Q10.)

–Statins commonly provoke muscle weakness and discomfort which can, in turn, lead to reduced levels of physical activity and increased resistance to insulin. (Thus the recently reported increases in diabetes with statin drug use.)

Are the physiologic effects of omega-3 fatty acids, present and necessary for health, at odds with the non-physiologic effects of statin drugs?

I fear we don’t have sufficient data to come to firm conclusions yet, but my perception is that the case against statins is building. Yes, they have benefits in specific subsets of people (none in others), but the notion that everybody needs a statin drug is, I believe, not only dead wrong, but may have effects that are distinctly negative. And I believe that the arguments in favor of omega-3 fatty acid supplementation, EPA and DHA (and perhaps DPA), make better sense.

 - See more at: http://blog.trackyourplaque.com/2013/06/are-statins-and-omega-3s-incompatible.html

Cholesterol and Why Statin Drugs are Harmful

Cholesterol and Why Statin Drugs are Harmful

 

 

For decades, health experts have told us to watch our cholesterol levels, lower our intake of saturated fats, and consume low-fat diets.

An estimated 102 million Americans have cholesterol levels higher than 200. More than 20 million Americans are on statin drugs to lower cholesterol.

In theory, if we were following recommendations from doctors, dietitians, fitness experts, and dutifully taking our medications, we should be see a reduction in disease.

But the fact is…
We don’t.

So, it’s important to ask…

• Does eating high cholesterol foods correlate to rising cholesterol levels?

• Do high cholesterol levels necessarily mean you are at higher risk for cardiovascular disease or heart attack?

• Is the use of statin drugs safe and useful in reducing the levels of cholesterol in the body, thus lowering our disease risk?

A recent government study shows that raising levels of HDL “good” cholesterol using a drug did not diminish the chance of heart disease.
From the NY Times:

“Patients taking the medicine along with Zocor had higher levels of H.D.L. and lower levels of triglycerides, a fat in the blood. Despite these seeming improvements, the patients fared no better and may have done slightly worse than those taking Zocor alone. That is why the entire theory behind trying to increase H.D.L. levels in patients with heart disease may need rethinking.

In 2010 the British Medical Journal published a study revealing that the use of statin drugs was connected to liver, muscle, eye, and kidney problems. The results showed increased risk of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy and cataracts.

Dietary cholesterol levels are not related to serum cholesterol levels

According to Nora Gedgaudas, of Primal Body – Primal Mind:

“No study to date has adequately shown any significant link between dietary and serum cholesterol levels…or any significant causative link between cholesterol and actual heart disease. Other than in uncommon cases of genetically based ‘familial hypercholesterolemia’ (where natural mechanisms which regulate cholesterol production fail and the body cannot stop overproduction-even here the proof of the problematic nature of cholesterol is dubious, at best), cholesterol is perhaps only potentially deleterious in and of itself in oxidized forms, occurring as a result of food processing methods (such as in “reduced fat” milks, powdered milk/eggs) and high heat cooking/frying. Inflammatory processes can also be oxidizing of cholesterol in the body. Other than this, ALL cholesterol in the body is the same. ‘HDL’ and ‘LDL’ only reflect transport mechanisms for healthy cholesterol and are meaningless measures of coronary heart disease risk (Enig, Ravnskov).

It is also important to realize that ‘HDL’ and ‘LDL’ are NOT actual cholesterol at all, but merely the protein transport mechanism for cholesterol. Again, All cholesterol is exactly the same. LDL takes cholesterol away from the liver to the extremities and other organs for various purposes and HDL merely returns the same cholesterol to the liver where it may be recycled.”

Gedgaudas believes it is more important to find out why your cholesterol levels are up. When we have stress, infections, clogged arteries, high carbohydrate diets which cause insulin resistance and diabetes, weight issues, free radical activity, and low thyroid function, these can cause the liver to produce more cholesterol in order to deal with excess inflammation. If cholesterol levels are rising, it’s always a sign of some underlying problem, but it doesn’t mean cholesterol is causing the problem.

Doctors are missing the problem

Prescriptions for high cholesterol go hand-in-hand with recommendations for low-fat diets. This type of diet is not only tasteless and unsatisfying, it is also grossly deficient in the most nutrient-dense and health supporting foods on the planet: foods with healthy fats and cholesterol.

In the last five years, doctors have started recommending that obese children take statin drugs. Of course, there is little to no thought given to the staples of the Standard American children’s diet: highly processed, increasingly lower and lower in fat ast time goes on, high-carb, sugary foods with little to no nutritional content.

It’s a wonder doctors don’t draw the obvious conclusion that these foods might possibly be the culprit to children’s health and obesity issues. But they don’t. What’s more, they fail to give good, sound nutritional advice. The result is that some children end up on drugs because apparently providing real, healthy foods that support growth and development is not what they believe will solve the problem.

Truths about cholesterol:

• Cholesterol is vital to health. Without it, we have hormonal, brain, heart, endocrine, and nervous system issues and damage. Lack of adequate cholesterol in the body leads to blood sugar imbalance, mineral deficiencies, chronic inflammation, infertility, allergies, and asthma.

• Cholesterol is beneficial to the gastrointestinal environment and lining because it improves cell-membrane integrity and can also help reduce excessive permeability of substances through the intestinal wall and into the bloodstream.

• Every cell in our bodies is made of cholesterol. Without it they would become leaky and porous, causing a flood of cholesterol taken from other parts of the body to repair damage.

• Cholesterol is the precursor to Vitamin D, which is now known to be a hormone rather than a vitamin, and is responsible for helping to digest fats, mineral metabolism, protecting bones, strengthening the immune system

• Cholesterol is a powerful anti-oxidant which protects the body from free-radical damage and aging

• The theory of cholesterol being unhealthy was originally created by food processing industries to villanize animal fats and products, which are direct competitors to vegetable oils, and also from the pharmaceutical industry to develop a market to sell cholesterol-lowering drugs. Lipitor and other Statin drugs are enormous profit-bringers for pharmaceutical companies.

Truths about statin drugs:

• Taking them only masks the problem going on in your body (for a little while) and doesn’t get to the cause of the problem, which is usually chronic inflammation due to poor dietary habits which cause nutritional deficiencies

• They deplete your body of vital nutrients, such as C0Q10, which is essential to heart health. Cardiologist Dr. Peter Langsjoen conducted a study involving 20 patients with completely normal heart function. Six months later, after being on 20 mg daily of Lipitor (a low dose), two-thirds of the patients were found to have abnormalities in the filling phase of the heart. Langsjoen’s conclusion was that this occurred due to the depletion of CoQ10. A lack of C0Q10 causes muscle pain and weakness, due to the prevention of energy being produced in the mitrochondria in the cell.

• These medications can also cause other types of muscle weakness and pain. In Denmark, researchers who studied 500,000 residents (approximately 9 percent of the population) discovered that those taking prescription medications to lower cholesterol were more likely to develop polyneuropathy, characterized as weakness and pain or tingling in the hands or feet and difficulty walking.

• They cause a marked decrease of cholesterol-production in the brain. According to Dr. Barry Sears, this leads to a loss of memory due to diminished production of new synaptic connections and loss of memory.

• They are costly in more ways than one: for your wallet and for your health. Eating healthy foods that naturally maintain normal cholesterol levels in the body costs less.

• They causes other side-effects, one of them being liver damage. Liver damage is dangerous and can lead to other health issues that are very unpleasant, expensive, and time-consuming to treat

Would the real enemies please stand up?

• Industrial fats – industrially-produced, polyunsaturated fats: canola, soybean, cottonseed, corn, peanut, safflower, and sunflower oils, shortening, butter substitutes and spreads, and other fake butter products. Some of these oils come from living things, but they are processed and chemically-altered which transforms them into trans-fats (even though the label may specifically read “no trans fats”), deodorized, and subjected to high- heat temperatures, rendering them nutritionally bankrupt and rancid.

• Sugar - which causes metabolic syndrome and blood sugar imbalance, leading to insulin resistance and diabetes, and heart attacks. In 2009, the United States was ranked 4th in sugar consumption levels in the world.

• Lack of nutrient-dense foods – modern diets are largely represented by nutritionally-deficient and heavily processed convenience foods which do not support the health of the human body. They cause build up in our arteries, liver damage, diabetes, premature aging, and cardiovascular disease.

• Stress - periods of stress deplete nutrients in the body causing inflammation, which triggers disease.

Watch this informative video by Dr. Mark Hyman about cholesterol:

How to keep inflammation and cholesterol levels normal in your body

Real, traditional fats from healthy animals and birds on pasture actually make us healthier because they are easy to digest and are some of the most nutrient-dense foods available. Looking back over the historical past, the human diet has always contained large amounts of fat and cholesterol.
Dr. Weston A. Price, author of Nutrition and Physical Degeneration, analyzed foods consumed by traditional, primitive peoples all over the world. In these populations, health was robust and disease nearly non-existent. He discovered that their diets allowed for at least four times the calcium and other minerals, and at least 10 times the fat-soluble vitamins and amino acids as the modern diet which were obtained from animal foods such as eggs, fish, shellfish, animal fats like butter, lard, and tallow, and organ meats. All these foods were high in cholesterol and fat.
If you want to maintain good health:

• Eat real, grass-fed butter

• Eat olive and coconut oil

• Eat grass-fed meats, poultry and pasture-raised eggs from reputable, local sources that raise their products sustainable

• Eat safe-sourced seafood

• Take cod liver oil

• Eat organic fruits and vegetables

• If you do eat grains, eat them sparingly and prepare them properly through soaking, sprouting, or fermenting. Eat grains with healthy fats such as milk, cream, butter, cheese, and other healthy foods containing fats such as olive oil, coconut oil, lard, tallow, bone marrow, and grass-fed meats and poultry.

• Avoid sugar – that means any refined carbohydrates – crackers, breads, rice cakes, cereals, pretzels, chips, bagels, pasta, desserts, sugary beverages (including juice and power “electrolyte” drinks).

• Avoid processed foods and drinks, and especially those with artificial sweeteners or high-fructose corn syrup

• Avoid unhealthy vegetable oils such as canola, soy, cottonseed, or safflower. These oils are too high in Omega 6s (which cause inflammation, cancer, and heart disease), are highly-processed at high temperatures making them rancid, and many of these oils are also likely to be genetically-modified as well, which has its own set of health risks.

• Lower stress levels with moderate and enjoyable exercise and relaxation strategies. Stress can severely deplete nutrients in the body, leading to heart disease.

For more information:
Importance of Dietary Fats
Cholesterol and Health – Chris Masterjohn
The Benefits of High Cholesterol – Weston A. Price Foundation
Dangers of Statin Drugs: What You Haven’t Been Told About Popular Cholesterol-Lowering Drugs – WAP Foundation
The Oiling of America – Sally Fallon and Dr. Mary G. Enig, PhD
I have high cholesterol, and I don’t care – The Healthy Skeptic
Medication Sense – Dr. Jay S. Cohen
Suggested reading:
Fat and Cholesterol are Good for You by Uffe Ravnskov, MD, PhD
The Cholesterol Delusion by Ernest N. Curtis, M.D.

This post is part of Sarah The Healthy Home Economist’s Monday Mania.

Healthy Men Should Not Take Statins Says JAMA - Dach

Healthy Men Should Not Take Statins Says JAMA by Jeffrey Dach MD

The title speaks for itself. This bombshell article by Rita Redberg, MD, editor of the Archives of Internal Medicine, appeared in April 2012 JAMA advising healthy men with high cholesterol to stay away from statin anti-cholesterol drugs, pointing out there is no mortality benefit.  Dr Redberg goes on with a list of adverse side effects of statin drugs,  namely, myopathy, cognitive dysfunction, etc.   This JAMA article and debate is an outgrowth of the "Less is More" series in the Archives of Internal Medicine.    For fairness, JAMA also posted the opposing view by Dr. Blaha. 

For your convenience, I have posted Dr. Rita Redberg's article here with links to the original.  Above left image: Statin Drug, Lipitor 40 mg tablets, Courtesy of The Week. Click Here for link to Dr Rita Redberg article in April 2012 JAMA.

-----------------------------------------------------------

Healthy Men Should Not Take Statins

by Rita F. Redberg, MD; Mitchell H. Katz, MD , 

Author Affiliations: Division of Cardiology, Department of Medicine, University of California, San Francisco (Dr Redberg); and Department of Health Services, County of Los Angeles, Los Angeles, California (Dr Katz).


Left Image: Courtesy of Wall Street Journal and Dr Rita Redberg.

Dr Redberg is also Editor, Archives of Internal Medicine. Dr Katz is also Deputy Editor, Archives of Internal Medicine.

Here is the Quote from the JAMA Article:

"Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature CHD be treated with a statin? — No "says Rita Redberg MD.

"Extensive epidemiologic data demonstrate that higher cholesterol levels are associated with a greater risk of heart disease. At the population level, higher levels of cholesterol are associated with a diet greater in fatty foods, particularly trans fat and meat, and low intake of fruits and vegetables.

The important questions for clinicians (and for patients) are as follows:

(1) does treatment of elevated cholesterol levels with statins in otherwise healthy persons decrease mortality or prevent other serious outcomes?

(2) What are the adverse effects associated with statin treatment in healthy persons?

(3) Do the potential benefits outweigh the potential risks? The answers to these questions suggest that statin therapy should not be recommended for men with elevated cholesterol who are otherwise healthy.

Benefits of Statin Therapy in Healthy Men With High Cholesterol?

Dr Ray Archives Int Med - NO Reduction in Mortality
    What is the benefit of statin therapy in healthy men with high cholesterol levels? Data from a meta-analysis of 11 trials including 65 229 persons with 244 000 person-years of follow-up in healthy but high-risk men and women showed no reduction in mortality associated with treatment with statins.(1 )

Cochrane Review - No Reduction in Mortality

A 2011 Cochrane review of treatment with statins among persons without documented coronary disease came to similar conclusions.(2) The Cochrane review also observed that all but one of the clinical trials providing evidence on this issue were sponsored by the pharmaceutical industry.

Biased Reporting in Industry Sponsored Drug Trials

It is well established that industry-sponsored trials are more likely than non–industry-sponsored trials to report favorable results for drug treatment because of biased reporting, biased interpretation, or both of trial results.(6)

Adverse Effects of Statins

What adverse effects are associated with statin treatment in healthy persons?

Myopathy, Muscle Pain, Weakness
All treatments designed to prevent disease—such as death from coronary disease—can also result in adverse effects. Data from observational studies show much higher rates for statin-associated myopathy and other adverse events in actual use than the 1% to 5% rate reported in clinical trials. This underestimation of adverse events occurs because the trials excluded up to 30% of patients with many common comorbidities, such as those with a history of muscular pains, as well as renal or hepatic insufficiency.(3)

Many randomized trials also excluded patients who had adverse effects of treatment during an open-label run-in period. For example, in the Treat to New Targets trial, after initial exclusions based on comorbidities, an additional 35% of eligible patients, or 16% of patients, were excluded during an 8-week, open-label, run-in phase because of adverse events, ischemic events, or participants' lipid levels while taking the drug not meeting entry criteria.7 Additionally, the results of randomized trials of statin treatment likely underestimate common symptoms such as myalgia, fatigue, and other minor muscle complaints because these studies often only collect data on more quantifiable adverse effects such as rhabdomyolysis.

Cognitive Impairment

    Numerous anecdotal reports as well as a small trial (8 - 9) have suggested that statin therapy causes cognitive impairment, but this adverse outcome would not have been captured in randomized trials. The true extent of cognitive impairment associated with statins remains understudied. It is disappointing that more data are not available on important adverse events associated with statin treatment, despite millions of prescriptions and many years of use. This information could be easily collected in observational studies and from registries. (8)(9)

One population-based cohort study in Great Britain of more than 2 million statin users found that statin use was associated with increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract.(4)

The risk of diabetes with statin use has been seen in randomized clinical trials such as JUPITER, which found a 3% risk of developing diabetes in the rosuvastatin group, significantly higher than in the placebo group.

In observational data from the Women's Health Initiative, there was an unadjusted 71% increased risk and 48% adjusted increased risk of diabetes in healthy women taking statins.(5)

Do the potential benefits outweigh the potential risks?

Based on all current evidence, a healthy man with elevated cholesterol will not live any longer if he takes statins. For every 100 patients with elevated cholesterol levels who take statins for 5 years, a myocardial infarction will be prevented in 1 or 2 patients.(7)

Preventing a heart attack is a meaningful outcome. However, by taking statins, 1 or more patients will develop diabetes and 20% or more will experience disabling symptoms, including muscle weakness, fatigue, and memory loss. (3)

NONDRUG APPROACHES TO REDUCING CORONARY RISK

There are effective methods for reducing cardiovascular risk in otherwise healthy men: dietary modification, weight loss, and increased exercise.

These strategies are effective in increasing longevity and also result in other positive benefits, including improved mood and sexual function (10) and fewer fractures. Although these strategies are challenging, prescribing a statin may undermine them. For example, some patients derive a false sense of security that because they are taking a statin they can eat whatever they want and do not have to exercise.

Belief in Benefits of Statins for Patients Without CAD

For some clinicians, evidence that statins reduce the risk of recurrent coronary events in patients with documented coronary disease leads to the belief that statins also “must” be beneficial for patients without coronary disease.

However, recent history is rife with examples of interventions that are proven to work in patients with serious disease yet are not efficacious when generalized to patients without serious disease.

CABG Not a Good Choice for Single Vessel Disease

For example, coronary artery bypass graft (CABG) surgery is lifesaving for patients with symptomatic left main disease. However, CABG surgery would not be a good choice for single-vessel coronary artery disease (CAD) because risks would outweigh benefits in less extensive CAD. Similarly, the benefits of carotid endarterectomy in preventing stroke outweigh the risks for symptomatic patients with tight carotid artery stenosis, but not for asymptomatic patients with less critical stenosis. In addition, the use of aspirin is similar to statins for prevention.

Aspirin Not Useful For Primary Prevention

The data show clear benefit for aspirin in secondary prevention of cardiovascular disease, but not for primary prevention. Practitioners should not be generalizing from other settings when good data indicate that statins are not effective in improving length or quality of life when used for primary prevention.

For the 55-year-old man in this scenario, his risk of myocardial infarction in the next 10 years based on the Framingham Risk Score varies from 10% to 20%. His risk is driven mostly by his age rather than by his cholesterol level. Increasing age has a much larger influence on risk for cardiovascular disease than do increasing levels of cholesterol.

Recent data on increased risk of diabetes, cognitive dysfunction, and muscle pain associated with statins suggest that there is risk with no evidence of benefit.

Advising healthy patients to take a drug that does not offer the possibility to feel better or live longer and has significant adverse effects with potential decrement in quality of life is not in their interest.

At the same time, there are significant opportunities for improvement in lifestyle counseling and interventions. Even small changes in diet and increases in physical activity and smoking cessation can lead to significant personal and population health benefits. Such positive lifestyle changes have the key advantage of helping patients feel better and live longer. Lifestyle counseling should remain the focus of primarily prevention efforts—at the physician and public health levels.

AUTHOR INFORMATION: Corresponding Author: Rita F. Redberg, MD, Division of Cardiology, University of California, San Francisco, 505 Parnassus Ave, M1180, San Francisco, CA 94143 (redberg@medicine.ucsf.edu).

Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.


Additional Contributions: We thank Deborah Grady, MD, University of California, San Francisco, for her input in the writing of this Viewpoint. She was not compensated for her contribution." end quote


REFERENCES1) Ray KK, Seshasai SR, Erqou S,  et al.  Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants.  Arch Intern Med. 2010;170(12):1024-1031, PubMed

2) Taylor F, Ward K, Moore TH,  et al.  Statins for the primary prevention of cardiovascular disease.  Cochrane Database Syst Rev. 2011;(1):CD004816
PubMed

3) Fernandez G, Spatz ES, Jablecki C, Phillips PS. Statin myopathy: a common dilemma not reflected in clinical trials.  Cleve Clin J Med. 2011;78(6):393-403. PubMed

4) Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database.  BMJ. 2010;340c2197. PubMed

5) Culver AL, Ockene IS, Balasubramanian R,  et al.  Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative.  Arch Intern Med. 2012;172(2):144-152. PubMed

6) Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review.  BMJ. 2003;326(7400):1167-1170 PubMed

7) LaRosa J, Grundy SM, Waters DD,  et al.  Intensive lipid lowering with atorvastatin in patients with stable coronary disease.  N Engl J Med. 2005;352(14):1425-1435 PubMed

8) Muldoon MF, Barger SD, Ryan CM,  et al.  Effects of lovastatin on cognitive function and psychological well-being.  Am J Med. 2000;108(7):538-546PubMed CrossRef

9) Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults.  Am J Med. 2004;117(11):823-829 PubMed CrossRef

10) Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis.  Arch Intern Med. 2011;171(20):1797-1803PubMed

-----

Links to Articles with Related Content:

You Tube Videos by Dr Dach:

Links to all four parts of this series on You Tube:

part one: http://youtube.com/watch?v=b-iUJd4IxRM

part two: http://youtube.com/watch?v=RozkhmdHPac

part three: http://www.youtube.com/watch?v=_To64-NWKao

Part four: http://youtube.com/watch?v=gd6f8_GjAsg

Links to related articles of interest:

Lipitor and The Dracula of Modern Technology by Jeffrey Dach MD
http://www.drdach.com/Lipitor_Jarvik_Dracula.html

Getting Off Statin Drug Stories
http://www.bioidenticalhormones101.com/Statin_Drug_Stories.html

How to Reverse Heart Disease with the Coronary Calcium Score by Jeffrey Dach MD
http://jeffreydach.com/2008/03/27/cat-coronary-calcium-scoring-reversing-hear...

Cholesterol Lowering Statin Drugs for Women, Just Say No
http://www.bioidenticalhormones101.com/Statin_Drugs_Women.html

Reversing Heart Disease without Drugs
http://www.drdach.com/wst_page7.html

Cholesterol Lowering Drugs for the Elderly, Bad Idea by Jeffrey Dach MD
http://jeffreydach.com/2008/08/30/cholesterol-lowering-drugs-for-the-elderly-...

A Choirboy for Cholesterol Turns Disbeliever by Jeffrey Dach MD
http://www.drdach.com/Cholesterol_Choirboy.html

More links and references

Listen to Debate Audio

http://www.ihi.org/knowledge/Pages/AudioandVideo/AIRShouldHealthyManBeTreatedWithaStatin.aspx
Audio of Debate on Statins for Healthy Men in JAMA article with  Dr Rita Redberg vs Michael Blaha (opposition)

Author in the Room: Should a Healthy 55-Year-Old Man Be Treated with a Statin?
Share on facebook Share on twitter Share on linkedin Share on print Share on email More Sharing Services

May 2012 Author in the Room® Teleconference

Authors and Articles:

Michael Blaha, MD, MPH, suggests that the available data do support treatment:
Statin Therapy for Healthy Men Identified as “Increased Risk”

Rita Redberg, MD, MSc, suggests that the available data do not support treatment.
Healthy Men Should Not Take Statins

Summary Points:Summary Points from Dr. Michael Blaha: High-quality literature supports statins for reduction of first heart attack and stroke, in addition to a mild decrease in all-cause mortality over 3 to 5 years.
    The key to efficient use of statins in primary prevention is risk stratification.
    We must demand high-quality evidence for benefit and for harm in a potentially beneficial medication class such as statins.
    Physicians should adhere to national guidelines to guide statin use in primary prevention.

http://www.healthnewsreview.org/2012/04/dueling-viewpoints-should-a-healthy-middle-aged-man-with-elevated-cholesterol-take-a-statin-drug/
Dueling viewpoints: Should a healthy middle-aged man with elevated cholesterol take a statin drug?  Posted by Gary Schwitzer in Journal practices

http://www.theheart.org/article/1383271.do
Should statins be used in primary prevention? JAMA gets in on the debate
April 10, 2012 Michael O'Riordan

http://www.dailymail.co.uk/debate/article-2147218/Should-everybody-fifty-Statins-reduce-health-risks.html
Should everybody over fifty take statins to reduce health risks?  By Dr Robert Lefever


http://www.vasculardoc.com/opinion-commentry/healthy-men-should-not-take-statin-drugs-for-cholesterol_133.aspx

Healthy men should not take statin drugs for cholesterol
Apr 12, 2012- In the latest issue of the Journal of the American Medical Association (JAMA – April 11, 2012) opposing viewpoints are offered by two leading cardiologists with regard to the following question:
Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature coronary artery disease, be treated with a statin?

http://www.jonbarron.org/heart-health/statin-drugs-jama-lower-ldl-cholesterol
Statin Drugs – the JAMA Debate - The April 14th issue of the Journal of the American Medical Association inaugurated a new feature called "Viewpoint" -- an "in magazine" debating forum for arguing out key medical issues of the day. Think of it like a civilized version of Dan Aykroyd and Jane Curtain's Point/Counterpoint sketches on Saturday Night Live.1
Date: 04/23/2012 Written by: Jon Barron

http://www.natap.org/2012/HIV/041112_01.htm
Should statins be used in primary prevention?
theheart.org April 12 2012 Michael O'Riordan
Baltimore, MD and San Francisco, CA - Differing opinions on the use of statins in primary prevention make the pages of one of the leading medical journals this week, with the Journal of the American Medical Association (JAMA) the latest in a line of professional and mainstream media outlets getting in on the contentious topic [1,2]. Introduced by the JAMA editors to encourage discussion and debate [3], the inaugural "dueling viewpoints" kicks off its new series by considering the clinical question of whether or not a healthy 55-year-old male with elevated cholesterol levels should begin taking the lipid-lowering medication.


http://anthonycolpo.com/?p=3479
Why Asians Should Ignore the Cholesterol Sham, and Why Healthy People Should Not Take Statins.  Anthony Colpo | Saturday, April 28th, 2012


http://www.minnpost.com/second-opinion/2012/04/duel-over-statins-use-healthy-people-moves-new-venue
'Duel' over statins' use in healthy people moves to new venue
By Susan Perry | 04/17/12

<<<<<<<<<<<<<>>>>>>>>>>>
http://cardiobrief.org/2012/01/23/rita-redberg-and-roger-blumenthal-clash-over-statins-for-primary-prevention-in-the-wall-street-journal/
January 23, 2012     
Rita Redberg and Roger Blumenthal Clash Over Statins for Primary Prevention in the Wall Street Journal 8    by Larry Husten • Uncategorized • Tags: mortality benefit, primary prevention   

The debate over whether statins should be used for primary prevention moved to the Wall Street Journal with opposing perspectives from cardiologists Roger Blumenthal and Rita Redberg.

Blumenthal argues that “there is a mountain of high-quality scientific evidence” to support the use of statins in people without known heart disease but “demonstrated to be at high risk for heart disease.”
Redberg argues that “for most healthy people, data show that statins do not prevent heart disease, nor extend life or improve quality of life. And they come with considerable side effects. That’s why I don’t recommend giving statins to healthy people, even those with higher cholesterol.”


http://www.lifediscoverywellness.com/archives.html
Healthy Men Should Not Take Statins-Neither should Women! 04/23/2012
Most of you know what cholesterol lowering drugs are.  Below is a list of the names of the most common drugs out there.  The most unethical event is taking place to people that you know and care about.  The amount of cholesterol drugs consumed is up and the drug companies bottom line has gone up, but there is no change in the amount of heart disease.  In fact heart disease is still the number one killer by far and it continues to go up and up and up.  So what in the health are the statins for?

    Advicor  (lovastatin with niacin) – Abbott
    Altoprev (lovastatin) – Shionogi Pharma
    Caduet [atorvastatin with amlodipine (Norvasc)] – Pfizer
    Crestor (rosuvastatin) - AstraZeneca
    Lescol (fluvastatin) – Novartis
    Lipitor (atorvastatin) - Pfizer
    Mevacor (lovastatin) – Merck
    Pravachol (pravastatin) -- Bristol-Myers Squibb
    Simcor (niacin/imvastatin) – Abbott
    Vytorin (ezetimibe/simvastatin) – Merck/Schering-Plough
    Zocor (simvastatin) – Merck


http://www.ucsfhealth.org/rita.redberg

Rita Redberg, F.A.C.C., M.Sc., M.D.

Cardiologist Dr. Rita Redberg is a cardiologist specializing in heart disease in women. She earned her medical degree from the University of Pennsylvania School of Medicine, in Philadelphia. She completed her residency at Columbia-Presbyterian Medical Center in New York, where she went on to complete a fellowship in cardiology. Then she completed a fellowship in non-invasive cardiology at Mount Sinai Medical Center, also in New York. In addition, Redberg has a masters of science in health policy and administration from the London School of Economics in England. Also she is currently a Robert Wood Johnson health policy fellow.
Redberg has written, edited and contributed to many books, including "You Can Be a Woman Cardiologist," "Heart Healthy: The Step-by-Step Guide to Preventing and Healing Heart Disease," and "Coronary Disease in Women: Evidence-Based Diagnosis and Treatment."

Clinics Cardiovascular Care and Prevention Center at Mission Bay
535 Mission Bay Blvd. South
San Francisco, CA 94158
Phone: (415) 353-2873
Fax: (415) 353-2528
Hours: Monday to Friday
8 a.m. – 5 p.m.

http://www.pace-cme.org/therapeutic-areas/opinion-statins-for-healthy-people
Statins for healthy people
Commentary by Prof John E Deanfield

Recently, prescribing statins to healthy people was discussed in the Journal of the American Medical Association. The main question is: should a healthy man aged 55 who has a blood pressure of 110 mm Hg, an LDL-cholesterol level of 6.46 mmol /L without family history take statins? Besides, the New England Journal of Medicine published a reflective publication on statins and the risk of diabetes. Links to these articles you will find below.

According to prof. John E. Deanfield (University College, London), statin therapy is a key part of multifactorial risk reduction strategies. Long term surveillance of risks and benefits are required, particularly for drugs given to very large numbers of people. The data we have so far are highly encouraging for statins.

Deanfield gives four good reasons to continue prescribing statins:

    The benefits of a healthy lifestyle should always be emphasised, but this is rarely adopted by patients.
    Statins provide an effective way of prolonging an event free survival and are generally safe, with increasing benefit over time.
    Thirdly the extremely well investigated potent statins atorvastatin and simvastatin are both generic and cheap
    It is important to consider the lifetime benefits of cardiovascular risk reduction in discussions with patients and not merely 5 and 10 year risks in those with cardiovascular disease..

References:

Healthy Men Should Not Take Statins :
JAMA. 2012;307(14):1491-1492. doi:10.1001/jama.2012.423
Rita F. Redberg, MD; Mitchell H. Katz, MD

Statin Therapy for Healthy Men Identified as “Increased Risk”
JAMA. 2012;307(14):1489-1490. doi:10.1001/jama.2012.425
Michael J. Blaha, MD, MPH; Khurram Nasir, MD, MPH; Roger S. Blumenthal, MD

Statins: Is It Really Time to Reassess Benefits and Risks?
N Engl J Med 2012; 366:1752-1755May 10, 2012
Allison B. Goldfine, M.D.

Wall Street journal - <<<<<<<<<<>>>>>>>>>>

http://online.wsj.com/article/SB10001424052970203471004577145053566185694.html

Should Healthy People Take Cholesterol Drugs to Prevent Heart Disease?


http://www.kardeanutrition.com/content/healthy-high-cholesterol-should-you-be-taking-statins

Healthy But With High Cholesterol: Should You Be Taking Statins?
Posted By Rob Leighton On 04/16/2012 - 8:05 am in the following categories :
Your healthy and feeling great, but you just found out that your LDL (bad) cholesterol is high. You do not have any of the standard risk factors, like a parent with heart disease.  Should you be taking a statin medication – perhaps for the rest of your life?

More and more doctors are coming to the conclusion that the answer is no.
In the April 2012 Journal of the American Medical Association (JAMA), two perspectives were presented.



Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
www.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

Click Here for: Dr Dach's Online Store for Pure Encapsulations Supplements
Click Here for: Dr Dach's Online Store for Nature's Sunshine Supplements

Web Site and Discussion Board Links:

jdach1.typepad.com/blog/
disc.yourwebapps.com/Indices/244124.htmldisc.yourwebapps.com/Indices/244066.htmldisc.yourwebapps.com/Indices/244067.htmldisc.yourwebapps.com/Indices/244161.htmldisc.yourwebapps.com/Indices/244163.html



Disclaimer click here: www.drdach.com/wst_page20.html

The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician -- patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.

Link to this article:
http://jeffreydach.com/2012/07/13/healthy-men-should-not-take-statins-says-jama-by-jeffrey-dach-md.aspx

Copyright (c) 2012-13 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.

FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.
==========================================================

Read the complete article here.