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New research identifies modifiable risk factors for heart disease

Emerging research on cardiovascular risk factors and treatment effects are helping clinicians gain a better understanding of which patients are most likely to benefit from close monitoring, lifestyle changes and/or additional therapeutic interventions. New findings published in the December 15/22, 2009, Prevention and Outcomes Focus Issue of the Journal of the American College of Cardiology aim to disentangle the influence of menopause versus chronological aging in upping women's post-menopausal risk for heart disease, evaluate the role of smoking status, physical activity and diet-induced weight loss in certain patient populations, and more fully describe the effects of intensive lipid-lowering therapy on subsequent cardiovascular events.

Highlights from select studies published in the current issue of JACC find:

Menopause Linked to Harmful Changes in Blood Cholesterol, But Not Other Cardiovascular Risk Factors

Whether the jump in heart disease risk among post-menopausal women is a function of aging or a consequence of the menopausal transition and the associated loss of endogenous estrogen, or both, has been hotly debated. A new study extensively followed 1,054 initially pre-menopausal or early peri-menopausal women of diverse ethnicities to assess changes in a wide variety of cardiovascular risk factors in relation to a women's final menstrual period. It is the first study to specifically identify the year immediately around the final menstrual period as the time of most adverse changes in the lipid profile of all women, according to authors.

Only total cholesterol, low-density lipoprotein cholesterol (LDL or "bad" cholesterol) and its protein carrier (apoB) increased substantially around the time of a woman's final menstrual period, consistent with menopause-induced changes. These unique increaseswhich were independent of age and other cofoundersoccurred in women of all weight levels and were similar across all ethnic groups, suggesting menopause has a uniform influence on lipids. Researchers found no changes in inflammatory or anticoagulation factors, blood pressure, or insulin and glucose related to a woman's final menstrual period; instead, these risk factors were consistent with a linear model, indicative of chronological aging.

Authors state these findings emphasize the need to closely monitor lipid profiles of pre-menopausal and peri-menopausal women, and encourage proven lifestyle changes and therapeutic interventions to try to counter and possibly prevent adverse changes in lipids due to menopausal transition. Participants in this 9-year study ranged in age from 42 to 52 years; they were not taking hormone therapy before menopause, were free of stroke, heart disease and diabetes at entry and were followed annually for nine years and experienced their final menstrual period during follow-up.

Never Smoking or Quitting Before or After an Initial Heart Attack Improves Long-Term Survival

According to a new study that followed 1,521 patients (≤65 years of age) over a median of 13.2 years, survivors of a first heart attack who never smoked had roughly one-half the risk of dying than those who continued to smoking following a heart attack. Moreover, data suggests smokers who quit before or after suffering a heart attack had a better chance of survival (a reduced mortality risk of 50 percent and 37 percent, respectively) compared with persistent smokers. According to the authors, this reduction appears to be at least as beneficial as other secondary preventive therapies, such as lowering cholesterol (a 29 percent reduction), aspirin (15 percent) and beta blockers (23 percent).

Among patients who continued smoking, reducing the number of daily cigarettes played a protective rolecutting out five cigarettes a day was associated with an 18 percent decline in mortality risk (p < 0.001). The majority of patients followed (73 percent) were current or former smokers. By assessing smoking status repeatedly over time, authors believe this study provides a more accurate picture of true smoking habits.

Interactive, Structured Physical Activity Lowers Blood Pressure and Improves Early Markers of Atherosclerosis in Pre-Pubertal Obese Children

Hypertension and initial signs of atherosclerosis develop before puberty in obese children, underscoring the urgent need to identify strategies to prevent the progression of heart disease in this population.

New research demonstrates for the first time that a regular and achievable physical activity program results in a significant reduction in systolic blood pressure and a decrease in arterial stiffness after 3 months, as well as stabilization of the intra-media thickness after 6 months in these children. These changes were found to be independent of body weight or fat loss and are of greater magnitude in children with high blood pressure, suggesting a direct effect of exercise on blood pressure lowering. Reductions in blood pressure were clinically relevant, ranging from -7 to -12 mmHg for SBP and -2 to -7 mm Hg for DBP. In the exercise group, the proportion of children with hypertension was reduced significantly from 50 percent to 37 percent at 3 months and 29 percent at 6 months. The exercise groups also had reductions in abdominal fat and increases in their aerobic fitness.

This trial enrolled 44 pre-pubertal children ages 6 to 11 years with body mass index over the 97th age- and sex-specific percentile. The children were randomized to 3 months of exercise training after school or remaining relatively inactive. After three months, both groups trained twice per week for another 3 months. Twenty-two lean children were recruited for baseline comparison.

Structured exercise sessions were supervised and deliberately made enjoyable for the children with activities including swimming and ball games. Each 60-minute session included 30 minutes of aerobic exercise at a heart rate corresponding to 55 to 65 percent of individual maximal cardiorespiratory fitness, followed by 20 minutes of strength work and 10 minutes of stretching and cool-down.

Diet-Induced Weight Loss in Obese Patients Appears to Promote Early and Beneficial Changes in Heart and Blood Vessel Structure and Function

In this study of 60 obese men and women (body mass index: 37 +/- 3 kg/m2), modest weight loss (an average of 22 lbs) led to early improvements in four important subclinical traits previously associated with adverse cardiovascular outcomes, including a reduction in the thickness of the heart muscle and blood vessel wall and improvements in left ventricular diastolic and systolic function. Although some studies have shown improvement in heart function among patients with morbid obesity who have undergone surgeries such as gastric bypass or gastric banding (where weight loss is typically >50 lbs), fewer studies have found benefit in obese individuals who have achieved modest weight loss by lifestyle modifications including diet and exercise.

While maximal weight loss occurred at 6 months, the maximal cardiovascular benefits lagged behind by 3 to 12 months for all measured variables. According to authors, this finding suggests that previous studies of obese subjects undergoing moderate weight losswhich typically involved smaller groups followed for a few months up to a yearmay have failed to show cardiovascular benefit.

All participants underwent a medical history, physical exam, and cardiac and vascular ultrasound studies at baseline and at 3, 6, 12 and 24 months after the start of the intervention. Two years after starting the diet intervention, subjects regained over half of the weight that had been lost. Although the maximum benefits of weight loss were somewhat diminished with subsequent weight regain, there was still a significant improvement in heart function and blood vessel wall thickness at two years compared with baseline measures. Whether the present findings translate into improved clinical outcomes requires further investigation.

More Intensive Cholesterol-Lowering Drugs Appear to Outshine Standard or Moderate Statin Therapy in the Prevention of Recurrent Cardiovascular Disease in Certain Patients; Stronger Statins Prevent Not Just First Heart Problem, but Also Second and Third Heart Attack

Two studies in this issue find that use of higher strength statin medications prevent not just a first cardiac event, but also a second or third event as well showing an even greater benefit of statin therapy than previously thought.

Data from over 14,000 patients from two large randomized lipid-lowering trials the Pravastin or Atorvastatin Evaluation and Infection Therapy-Thrombosis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Incremental Decreases in End Points through Aggressive Lipid Lowering (IDEAL) trials were analyzed in a new way to count the total number of heart problems. Traditionally, trials are analyzed based on the time to first cardiovascular event and, as a result, statistical analyses did not include subsequent cardiovascular events. Results from the expanded analyses of the PROVE-IT and IDEAL data found intensive statin therapy to be more effective than standard or moderate statin therapy in preventing additional atherosclerotic development and future cardiovascular events. When additional events are considered, the total number of events prevented by more intensive lipid-lowering therapy was substantially greater.

As previously reported by PROVE-IT, first primary end point events (death, heart attack, stroke, UA requiring rehospitalization, or revascularization) were reduced by 16 percent with atorvastatin 80 mg (intensive lipid lowering) versus pravastatin 40 mg (moderate lipid lowering) (n = 464 vs. n = 537, respectively; p = 0.005). When reexamining the data to include recurrent cardiovascular events during the two-year follow up, authors found additional events were reduced by 19 percent with atorvastatin 80 mg versus pravastatin 40 mg (n = 275 vs. n = 340, respectively; p = 0.009), resulting in 138 fewer total primary events during follow-up. Based on this reanalysis which considers total events, the authors calculate that 14 patients need to be treated to prevent one eventa much smaller number than the 26 needed-to-treat to prevent the first occurrence of the primary end point.

A post-hoc analysis of the IDEAL trial provides new insights into the treatment of patients experiencing repeated occurrences of cardiovascular disease, and shows that high-dose statin therapy remains highly effective. In fact, compared with patients taking simvastatin 20 to 40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17 percent (p < 0.0001), of a second by 24 percent (p < 0.0001), of a third by 19 percent (p = 0.035), of a fourth by 24 percent (p = 0.058), and of a fifth by 28 percent (p = 0.117). There was a 17 percent overall reduction in risk across all five events.


Contact: Amanda Jekowsky
American College of Cardiology

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