Heart Failure Mortality Linked to Glucose Levels - Fiore

Heart Failure Mortality Linked to Glucose Levels

 

By Kristina Fiore, Staff Writer, MedPage Today

Published: January 17, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

• Note that, among patients with acute heart failure, an elevated admission blood glucose level was associated with 30-day mortality in this prospective observational cohort study.

 

• Be aware that serial glucose measurements were not available, limiting the ability to understand any potential effects of hyperglycemia treatment.

 

Serum glucose measured at the time of hospital admission predicted 30-day mortality in acute heart failure patients, researchers reported.
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“Our results are consistent with basic and clinical science data linking an elevated blood glucose level with myocardial injury, impaired myocardial performance, arrhythmia, and risk of ventricular remodeling,” they wrote.

Elevated glucose has also been associated with worse outcomes for patients with stroke and other critical illnesses, the researchers said, but its short-term prognostic impact in acute heart failure isn’t known.

Mebazaa and colleagues analyzed data from a multi-national cohort of 6,212 acute heart failure patients who had a mean age of 72, and 41% of whom had a previous diagnosis of diabetes.

The mean blood glucose concentration on arrival at the hospital was 7.5 mmol/L (135 mg/dL), and after 30 days, 10% of the patients had died.

Mebazaa and colleagues found that patients who died had a significantly higher median blood glucose concentration at admission compared with survivors ...

The risk between blood sugar levels and 30-day mortality was consistent across all subgroups of patients, the researchers reported,
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They also emphasized that the relationship between blood sugar and death was seen in patients both with and without a previous diagnosis of diabetes.

In sensitivity analyses, adjusting for factors such as left ventricular ejection fraction (LVEF) and plasma natriuretic peptides, as well as excluding patients from the largest cohort, didn’t significantly alter any of the findings.
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The researchers said it was not clear whether elevated blood sugar in acute heart failure is “a marker for risk or a mediator of adverse outcomes” — but since serum glucose is “widely measured, easily interpreted, and inexpensive to measure,” using it in risk assessment is “worthy of consideration.”
The study was limited by a lack of data on glycated hemoglobin (HbA1c) at admission and by the absence of serial measurements of glucose during the hospital stay.

Further work is needed to better understand the pathophysiology and complete trajectory of hyperglycemia in acute heart failure, they concluded.
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Noncardiac Benefits of Statins Found Lacking

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By Kristina Fiore, Staff Writer, MedPage TodayPublished: May 21, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

 

 

Claims of unintended benefits of statins appear to be largely unsubstantiated and known risks -- including liver and renal problems and myopathy -- confirmed, British researchers concluded based on findings from a large prospective open cohort study.

The study involving more than two million people, "largely confirmed other studies that reported no clear association between statins and risk of cancers," Julia Hippisley-Cox, MD, and Carol Coupland, MD, of the University of Nottingham in England reported online in BMJ.

The sole exception was esophageal cancer, the risk for which appeared to decrease with statin use. Men and women on simvastatin, for instance, had a 31% reduced risk of the disease (95% CI 0.50 to 0.94), and men on atorvastatin had a 27% reduced risk (95% CI 0.55 to 0.96).

On the other hand, they found that statins were associated with an increased risk of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataracts.

Cox and Coupland also calculated numbers needed to treat to see a benefit for cardiovascular disease, and to harm for other outcomes.

They found that for women at high risk of heart disease, the number needed to treat to prevent one case over five years was 37. For men, it was 33.

With regard to esophageal cancer, the number needed to treat to prevent one cancer case was substantially higher -- at 1,266 among women and 1,082 among men.

For adverse outcomes among women, the number needed to harm for an additional case of acute renal failure over five years was 434, 259 for myopathy, 136 for liver dysfunction, and 33 for cataract.

Those numbers were similar among men, except for myopathy, which was significantly lower at 91.
Statins are among the most widely prescribed medicines, and researchers say their use is likely to continue to increase. For example, in February, the FDA approved rosuvastatin (Crestor) for primary prevention of cardiovascular disease. (See FDA Okays Statin for Primary Prevention)
Other studies have investigated potential benefits of statins in a variety of conditions, including multiple sclerosis and colorectal cancer.

Still, the literature remains unclear as to the full range of risks and benefits of the drugs, Cox and Coupland wrote.

To quantify unintended effects of statins, the researchers conducted a prospective open cohort study involving 368 general practices in England and Wales that participate in the QResearch database.
A total of 2,004,692 patients ages 30 to 84 were involved in the cohort, and about 11% were new users of statins -- 70.7% were prescribed simvastatin, 22.3% atorvastatin, 3.6% pravastatin, 1.9% rosuvastatin, and 1.4% fluvastatin.

The primary outcome was the first recorded occurrence of any malady -- including cardiovascular disease, liver dysfunction, renal failure, venous thromboembolism, Parkinson's disease, dementia, rheumatoid arthritis, cataract, osteoporotic fracture, gastric cancer, esophageal cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.

Besides the lack of relationship with all but esophageal cancer, the researchers found no association between statins and risk for Parkinson's disease, rheumatoid arthritis, venous thromboembolism, dementia, or osteoporotic fracture.

Risks for liver and kidney problems,  myopathy, and cataracts were generally similar across statin types, except for liver dysfunction, in which risk was highest for fluvastatin. In women, risk of liver dysfunction was increased 2.53-fold with that statin (95% CI 1.84 to 3.47) and in men it was 1.97-fold higher (95% CI 1.43 to 2.72).

There was generally a dose-response effect for both renal failure and liver dysfunction.

The good news, the researchers found, was that after stopping statin therapy, the risk of developing cataracts returned to normal within a year, and the risk of acute renal failure and liver dysfunction did so within one to three years.

The researchers said that further study is needed in order to confirm the associations and to understand which patients are at the highest risk of adverse effects so that they can be monitored safely.

Overall, they said, the findings "would tend to support a policy of using lower doses of statins in people at high risk of the adverse event."

In an accompanying editorial, Alawi A. Alsheikh-Ali, MD, of Sheikh Khalifa Medical City in Abu Dhabi in the United Arab Emirates, and Richard H. Karas, MD, of Tufts University in Boston, said the findings are "reassuring" in that they didn't find an association between statins and a host of diseases.

"Statin use is not associated with cancer, severe muscle toxicity is rare, and liver abnormalities seem to be reversible, which is consistent with analyses of trial data," they wrote.

Still, they cautioned that physicians "should not overstate the benefits of statins."

"It would be wise to interpret the present observations in the context of the confirmed cardioprotective effects of statins," they wrote, "and remind ourselves and our patients that these drugs, although considered safe, are, like any intervention in medicine, not entirely free of adverse events."

Primary source: BMJ
Source reference:Cox JH, Coupland C "Unintended effects of statins in men and women in England and Wales: Population based cohort study using the QResearch database" BMJ 2010; DOI: 10.1136/bmj.c2197.
Additional source: BMJ
Source reference:Alsheikh-Ali AA, Karas RH "Balancing the intended and unintended effects of statins" BMJ 2010; DOI: 10.1136/bmj.c2197.
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