Metabolic Syndrome a Major Predictor of Heart Disease
The metabolic syndrome is a better predictor of cardiovascular risk in women than the popularized body mass index, said researchers for the multicenter Women’s Ischemia Syndrome Evaluation (WISE) study that appears in this week’s issue of the journal Circulation (Circulation 2004;109:706–713).
When women have myocardial ischemia, metabolic syndrome is a good indicator of grave cardiovascular risk, whereas body mass index does not appear to have a significant role in such predictions, said Steven Reis, MD, Associate Professor of Medicine at the University of Pittsburgh School of Medicine. Dr Reis is senior author of the study.
A total of 780 women, ages 21 to 86 years, were enrolled in the study. Researchers determined their metabolic syndrome status and referred them for coronary angiography to determine if they had myocardial ischemia. Their baseline evaluations included demographic factors, risk for coronary artery disease, regular medicine use, medical history, physical examinations, and a sample of blood taken after fasting. The blood was evaluated for lipids, glucose, insulin, presence of reproductive hormones, and inflammatory factors.
They were monitored an average of 3.5 years. A total of 41 women in the study died. In the women who had diabetes and metabolic syndrome, those who were normal weight had a 3.1-times higher adjusted odds of having significant coronary disease. Those who were overweight had 2.6-times higher odds, and those who were obese had 1.9-times higher odds. The 3-year survival rate was 97.2% in the women with normal metabolic status, compared with 91.5% for women with metabolic syndrome or diabetes. For those with diabetes or metabolic syndrome, 3-year, event-free survival was nominally better in those who were obese or overweight compared with those of normal weight. Women of normal weight with metabolic syndrome had a significantly increased rate of cardiovascular risk. Obese or overweight women whose metabolism was normal had a low cardiovascular risk.
“These results suggest that the clinical evaluation of abnormal metabolism (metabolic syndrome and diabetes) should play a more important role than determination of obesity alone in cardiovascular risk stratification in women,” said Kevin Kip, PhD, lead study author and Assistant Professor of Epidemiology at the University of Pittsburgh Graduate School of Public Health, in a released statement. “One possible explanation for this finding is that measurement of BMI [body mass index] to define overweight and obesity does not quantify the magnitude or ratio of subcutaneous-to-visceral fat in a given individual. The visceral fat area, which is associated with insulin resistance, appears to be an important link among many components of the metabolic syndrome, such as dyslipidemia and hypertension.”
Natriuretic Peptides: What Do They Mean?
Natriuretic peptide levels can predict risk of a variety of heart-related diseases, from heart failure to stroke or transient ischemic attack, said researchers from the Framingham Heart Study in Framingham, Mass, in a report that appears in the February 12, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:655–663OpenUrlCrossRefPubMed).
In this study, led by Thomas J. Wang, MD, of the Framingham study, researchers prospectively studied 3346 people without heart failure, examining the relationship of plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide levels to the risk of death from any cause, a first major cardiovascular event, heart failure, atrial fibrillation, stroke or transient ischemic attack, and coronary heart disease. During the follow-up period of 5.2 years, 119 subjects died, and 79 experienced a first cardiovascular event. Increasing levels of B-type natriuretic peptide were associated with first cardiovascular event, all-cause death, heart failure, atrial fibrillation, and stroke or transient ischemic attack. They were not, however, associated with risk of coronary heart disease events. Results were similar for N-terminal pro-atrial natriuretic peptide.
The researchers concluded that plasma natriuretic peptide levels predicted risk once they were adjusted for more traditional risk factors.
“Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure,” they wrote. “Although these data raise the possibility that measurement of natriuretic peptides may aid in the early detection of cardiovascular disease, additional investigations are needed to validate our results and to evaluate the screening characteristics of these peptides, including comparisons with markers that were not investigated in our study (eg, C-reactive protein). Further studies are also warranted to determine whether a finding of elevated plasma natriuretic peptide levels in asymptomatic persons should trigger further diagnostic tests, such as echocardiography.”
In an accompanying editorial (N Engl J Med. 2004;350:718–719), Daniel B. Mark, MD, MPH, and G. Michael Felder, MD, of the Duke University Medical Center and Duke Clinical Research Institute in Durham, NC, explain: “B-type natriuretic peptide and atrial natriuretic peptide are peptide hormones released in response to myocyte stretch.”
“Levels of B-type natriuretic peptide above the 80th percentile in this cohort (ie, higher than 20 pg per milliliter) were associated with an increase by more than 60 percent in the long-term risk of death. Furthermore, there was a significant prognostic gradient with respect to the risk of heart failure, atrial fibrillation, and stroke among the three levels of B-type natriuretic peptide (low, intermediate, and high) examined. This remarkable finding strongly suggests that there are important prognostic data even in the range of B-type natriuretic peptide levels thought, on the basis of previous studies, to rule out heart failure (ie, levels below 100 pg per milliliter),” they explained further.
High Iron Levels in Blood Associated With Type 2 Diabetes
When women with no known risk of diabetes are found to have higher amounts of iron stored in their blood, the risk of developing type 2 diabetes is increased, said researchers from Harvard School of Public Health in the February 11, 2004, issue of the Journal of the American Medical Association (JAMA. 2004;291:711–717OpenUrlCrossRefPubMed).
Excessive iron stores found in patients with hemochromatosis (caused by a genetic defect in iron absorption regulation) can cause type 2 diabetes in these individuals. Using the 32 826 women who provided blood samples in the Nurses’ Health Study, Rui Jian, MD, DrPH, and his colleagues evaluated biomarkers of iron storage in relation to the development of type 2 diabetes.
Of the 32 826 women in the study (none of whom had been diagnosed with diabetes, cardiovascular disease, or cancer), 698 developed diabetes during 10 years of follow-up. They were compared with 716 women from the study who did not develop diabetes.
The authors wrote: “Overall, women who subsequently developed diabetes during follow-up were heavier, more likely to have a family history of diabetes, less likely to exercise and consume alcohol, and had higher plasma concentrations of CRP [C-reactive protein], fasting insulin, and hemoglobin A1c at baseline. In addition, diabetic women tended to have higher baseline average intake of heme iron [a type of iron], transfat, red and processed meats, total calories, and lower intake of cereal fiber and magnesium.”
They concluded that the finding might have important implications for preventing type 2 diabetes and identifying individuals at increased risk for developing the disease.
HDL and NO—A Heart-Healthy Combination?
Phospholipids associated with the “good” cholesterol, high-density lipoprotein (HDL), stimulate the production of nitric oxide (NO) by blood vessel walls, said Bodo Levkau, MD, and colleagues from the Universitätsklinikumin Essen, Germany, in a report in the February 16, 2004, issue of the Journal of Clinical Investigation (J Clin Invest. 2004;113:569–581OpenUrlCrossRefPubMed).
In the study, the authors show how HDL stimulates the release of NO. NO causes blood vessels to relax and blood pressure to decrease.
Depression and Heart Disease: A Risk for Older Women?
Older women who have symptoms of depression may face an increased risk of heart disease and death, said researchers from the Albert Einstein College of Medicine in the Bronx, NY, in a report in the February 9, 2004, issue of the Archives of Internal Medicine (Arch Intern Med. 2004;164:289–298OpenUrlCrossRefPubMed).
The study, led by Sylvia Wassertheil-Smoller, PhD, of Albert Einstein College of Medicine, involved the 93 676 women who participated in the Women’s Health Initiative Observational Study, the largest health study ever conducted of women. As part of the study, the women were evaluated for symptoms of depression and risk factors for cardiovascular disease. All were monitored for an average of 4.1 years.
Women who reported symptoms of depression were 12% more likely to have high blood pressure and 60% more likely to have had a stroke or angina. Women with no history of cardiovascular disease who had depression faced a 50% increased risk of death from cardiovascular disease and a 32% increase risk of death from any cause.
The authors wrote: “A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD [cardiovascular disease] death and all-cause mortality [death from any cause], even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.”