Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease (CVD) risk factors, overall and by geographical region, at study baseline. METHODS: The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram (n = 4019; North America, 11%; Europe/Australia/Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female). RESULTS: About 58.3% (n = 2344) of the participants had at least one CVD risk factor and 18.9% (n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/Australia/Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% (P-value < 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) risk scores or used to define a favourable risk profile. CONCLUSIONS: CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed.

Effect of statin therapy in reducing the risk of serious non-AIDS-defining events and nonaccidental death.

BACKGROUND: Excessive inflammation persists despite antiretroviral treatment. Statins decrease cardiovascular (CV) disease risk by reducing low-density lipoprotein cholesterol and inflammation. We performed an exploratory analysis to evaluate whether statin therapy decreased risk of non-AIDS-defining events and nonaccidental death. METHODS: A total of 3601 subjects not on a statin from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort were included. Outcome was time to first clinical event (CV event, renal or hepatic disease, incident diabetes, thrombotic/embolic event, nontraumatic fracture, non-AIDS-defining malignancy, serious bacterial infection, or nonaccidental death); event categories were also analyzed separately. Inverse probability of treatment and censoring weighted Cox proportional hazard models were used to assess the causal statin effect. Differential statin effects by baseline covariates were evaluated. RESULTS: Over 15 135 person-years (PY) of follow-up, 484 subjects initiated statins; 616 experienced an event (crude event rate, 4.4/100 PY on a statin and 4.1/100 PY not on a statin); the unadjusted hazard ratio (HR) was 1.17 (95% confidence interval [CI], .91-1.50). In a final weighted model, the adjusted HR (AHR) was 0.81 (95% CI, .53- 1.24). Results for other clinical events were similar, except for malignancies (AHR, 0.43 [95% CI, .19-.94]) and bacterial infections (AHR, 1.30 [95% CI, .64-2.65]). No differential statin effects by baseline covariates were detected. CONCLUSIONS: Although statin therapy was not associated with a reduction in time to all non-AIDS-defining event or nonaccidental death, it was associated with a statistically significant 57% reduction in non-AIDS-defining malignancies. Confirmatory studies are needed to evaluate statin-associated reduction in risk of cancer and non-AIDS-associated morbidities.

Putting the Diabetes Prevention Program into practice: a program for weight loss and cardiovascular risk reduction for patients with metabolic syndrome or type 2 diabetes mellitus.

BACKGROUND: The increasing incidence and prevalence of metabolic syndrome and type 2 diabetes mellitus (DM) have significant implications on health world-wide. Large clinical trials have demonstrated the effectiveness of a comprehensive lifestyle program with a goal of moderate weight loss (5-7%) and regular exercise (150 minutes/week), resulting in a significant decrease in the incidence of type 2 DM and cardiovascular risk. METHODS: This study reports on the translation of the multi-center Diabetes Prevention Program (DPP) into a cardiac rehabilitation program, utilizing the expertise and experience of a cardiac rehabilitation program staff. The study adapted materials from the DPP to develop a program that fit local needs for diabetes prevention. RESULTS: Most participants completed the program (11 months) and their moderate weight loss was maintained for 11-12 months. At 11-12 months, waist circumference was reduced by approximately 2 inches, percent body fat was reduced by 5% (11% relative decrease, p<.05), weight was decreased by 10.1 pounds (p<.05), and blood pressure was reduced 8/3 mm Hg (p<.05). Exercise, nutrition, glucose, triglycerides, LDL-cholesterol and HDL cholesterol were all were significantly improved at 11-12 months (p<.05). CONCLUSIONS: Efforts to improve lifestyle and reduce body weight are important to patients at risk of developing diabetes. This program demonstrates that an intensive effort can significantly improve lifestyle and reduce body weight in patients with DM or at risk for DM. A program that simulates cardiac rehabilitation, translated from a successful clinical trial into practice, resulted in significant reduction and improvement in metabolic outcomes and cardiovascular risk. Support for cardiac rehabilitation from insurers to develop similar programs is encouraged and deserves further study.

The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia.

OBJECTIVES: The goal of this study was to determine the long-term effects of statins and antioxidant vitamins on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. BACKGROUND: Lipid-lowering therapy and antioxidant vitamins improve endothelium-dependent vasodilation in young and middle-aged adults with hypercholesterolemia, but their effects in older adults are not known. METHODS: Two double-blind, placebo-controlled studies were performed in individuals > or =70 years old with low-density lipoprotein cholesterol (LDL-C) > or =140 mg/dl. In the first study, 37 subjects were randomized to receive (group 1) pravastatin for six months then pravastatin and vitamin E for six additional months or (group 2) vitamin E for six months, then pravastatin and vitamin E for six additional months. In the second study, additional 17 subjects sequentially received simvastatin for six months, then simvastatin and vitamins C and E for six additional months. Flow-mediated vasodilation of the brachial artery was measured by high-resolution ultrasound. RESULTS: At baseline, subjects in both studies were similar in age (mean +/- SD, 75.8 +/- 4.2 years), gender, systolic blood pressure, total cholesterol (261.6 +/- 37.4 mg/dl), LDL-C (180.3 +/- 28.1 mg/dl), high-density lipoprotein cholesterol and triglycerides levels. Flow-mediated vasodilation was severely impaired (2.2 +/- 3.9%). Both statins reduced total and LDL-C levels (p < 0.001); however, neither statin, antioxidant vitamin regimen nor the combination of statins and antioxidant vitamins improved flow-mediated vasodilation of the brachial artery. At baseline, nitroglycerin-mediated vasodilation also was impaired (10.7 +/- 5.6%) and did not change in either study. CONCLUSIONS: Older adults with hypercholesterolemia have impaired flow-mediated vasodilation of the brachial artery that does not improve after one year of therapy with statins and antioxidant vitamins, despite significant lipid-lowering.

Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction.

BACKGROUND: Human immunodeficiency virus protease inhibitors (HIV PIs) are associated with hyperlipidemia, hyperglycemia, and obesity; however, it is not known whether they increase risk of atherosclerotic vascular disease. The purposes of this study were to characterize the lipoprotein abnormalities associated with use of HIV PIs in individuals with HIV infection and to determine the pathophysiological significance of these changes by assessing their effect on endothelial dysfunction. METHODS AND RESULTS: This was a cross-sectional study of 37 adults with HIV-1 infection who were receiving antiretroviral therapy. Twenty-two were taking HIV PIs (group 1); 15 were not (group 2). Lipids and lipoproteins were measured by enzymatic techniques and nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was measured by high-resolution ultrasound. Subjects in both groups were similar in regard to age, time since diagnosis of HIV infection, and CD4 cell count. Group 1 subjects had higher total cholesterol (5.68 versus 4.42 mmol/L, P=0.007) and triglyceride (4.43 versus 1.98 mmol/L, P=0.009) levels, characterized by elevated levels of IDL and VLDL. Subjects in group 1 had impaired FMD (2.6+/-4.6%), indicative of significant endothelial dysfunction. Group 2 subjects had normal FMD (8.1+/-6.7%, P=0.005). In group 1, chylomicron, VLDL, IDL, and HDL cholesterol levels predicted FMD. CONCLUSIONS: Use of HIV PIs is associated with atherogenic lipoprotein changes and endothelial dysfunction. Because these metabolic and vascular changes predispose to atherosclerosis, monitoring and treatment of dyslipidemia in patients taking these medications is warranted.

Managing dyslipidemia in older adults.

OBJECTIVES: To summarize and critically review clinical trial data regarding dyslipidemia as a risk factor for coronary heart disease (CHD) and the efficacy and safety of lipid-lowering interventions in older adults. Based on these data, clinical recommendations for diagnosing and managing dyslipidemia in older adults are provided. METHODS: Peer-reviewed journal articles were identified by a MEDLINE search and a review of journal article references. Studies that were performed exclusively in subjects older than 65 years or that included a large subgroup of older adults were included. CONCLUSIONS: Elevated low density lipoprotein and total cholesterol levels are independent risk factors for CHD events in patients aged older than 65 years. Older adults have a higher risk of mortality attributable to hypercholesterolemia. Diet and lipid-lowering medications safely and effectively lower cholesterol levels in this age group. Exercise increases high-density lipoprotein cholesterol levels and decreases triglyceride levels. If accompanied by weight loss, exercise may reduce low-density lipoprotein and total cholesterol levels. Improving lipid levels in older adults with CHD decreases the risk of future coronary events by up to 45%, and significant effects on outcome measures may be observed within 2 years of the initiation of therapy.

Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease.

BACKGROUND: In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). METHODS AND RESULTS: Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, P<0.001). After ingestion of grape juice, lag time increased by 34.5% (P=0.015). CONCLUSIONS: Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.

Transesophageal echocardiography for the evaluation and management of patients with cerebral ischemia.

To prevent recurrent strokes and transient ischemic attacks, considerable attention is devoted to investigating the etiology of acute cerebral ischemia in the large subpopulation of patients without an easily identifiable cause. In general, transthoracic echocardiography is an insensitive tool for the evaluation of patients with cerebral ischemia, unless clinical signs and/or symptoms of cardiac disease are present. Transesophageal echocardiography (TEE), because of its increased sensitivity for aortic arch atheromata, atrial septal pathology, left atrial thrombi, and valvular abnormalities, is the preferred cardiac imaging modality, especially in young patients, older patients with hypertension or systemic atherosclerosis, and patients with prosthetic heart valves. This paper reviews the prognostic and therapeutic impact of TEE in patients with cerebral ischemia, specifically focusing on the ability of information obtained by this technique to alter patient management and improve risk stratification.

Transient effusive-constrictive pericarditis due to chemotherapy.

Commonly used chemotherapeutic agents, specifically cytarabine and daunorubicin, can cause effusive-constrictive pericarditis. We describe a case of transient effusive-constrictive pericarditis in a patient with acute myelogenous leukemia. This is the first case report of a patient with transient effusive-constrictive pericarditis due to chemotherapy.

Gender differences in acute myocardial infarction: the University of Wisconsin experience.

OBJECTIVE: To investigate gender differences in baseline characteristics, presentation, and treatment of patients with acute myocardial infarction (MI) admitted to the University of Wisconsin Hospital Coronary Care Unit (CCU) over a 1-year period. METHODS: A retrospective review was performed on the charts of all patients (n = 293) admitted to the CCU in 1996 with a discharge diagnosis of acute MI. In 83 women and 187 men with analyzable data (n = 270), 42 factors related to baseline characteristics, presentation, treatment, and outcomes were identified and analyzed for gender differences. RESULTS: On average, women were 5 years older than men (p < .01). By univariate comparison, women were less likely than men to be smokers (p < .001); more likely to have underlying hypertension (p < .01), diabetes mellitus (p < 0.05), non-Q-wave infarctions (p < .01), and congestive heart failure (CHF, p < .05); and more likely to have received diuretics (p < .001) and ACE inhibitors (p < .01). While women were less likely than men to undergo coronary angiography (p < .05) and more likely to have echocardiograms (p < 0.05), rates of coronary artery bypass graft surgery, angioplasty, and the use of thrombolytics were similar for men and women. Clinical outcomes were similar in both groups. CHF, hypertension, and use of ACE inhibitors remained the only significant gender differences when data were adjusted for age. CONCLUSION: Comparing men and women with acute MI at UW Hospital revealed some differences in clinical characteristics and management. Except for CHF, hypertension, and use of ACE inhibitors (all of which may be related), these differences disappeared when the data were adjusted for age. This is particularly notable for the disappearance of the difference in the use of coronary angiography between men and women. The comparable use of beta-blockers, aspirin, and nitrates, and the similar clinical outcomes in men and women, suggest less gender difference in MI management at UW Hospital than reported in other studies.

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography.

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.

Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. off.

Hyperhomocysteinemia has recently been identified as an important risk factor for atherosclerotic vascular disease. This article reviews homocysteine metabolism, causes of hyperhomocysteinemia, the pathophysiological findings of this disorder, and epidemiological studies of homocysteine and vascular disease. Screening for hyperhomocysteinemia should be considered for patients at high risk for vascular disease or abnormalities of homocysteine metabolism. For primary prevention of vascular disease, treatment of patients with homocysteine levels of 14 micromol/L or higher should be considered. For secondary prevention, treatment of patients with homocysteine levels of 11 micromol/L or higher should be considered. Treatment is most conveniently administered as a folic acid supplement (400-1000 microg) and a high-potency multivitamin that contains at least 400 microg of folate. Higher doses of folic acid and cyanocobalamin supplements may be required in some patients. Until prospective clinical trial data become available, these conservative recommendations provide a safe, effective, and evidence-based approach to the diagnosis, evaluation, and management of patients with hyperhomocysteinemia.

Treatment of severe hypertriglyceridemia lowers plasma viscosity.

Elevated plasma viscosity is a predictor of atherosclerotic vascular disease and is a potential mechanism by which hypertriglyceridemia increases cardiovascular risk. Previous studies of plasma viscosity reduction in hypertriglyceridemic patients used medications that lowered both triglyceride and fibrinogen levels. Because fibrinogen is a major determinant of viscosity, it is unclear whether triglyceride reduction alone is sufficient to reduce plasma viscosity. The purpose of this study was to determine whether triglyceride-lowering therapy reduces plasma viscosity. This was a prospective study of 24 adult patients with severe hypertriglyceridemia (> or = 5.67 mmol/l). Fasting lipid, total serum protein, fibrinogen, plasma viscosity and serum viscosity levels were measured before and after therapy with 1200 mg/d of gemfibrozil. Triglyceride levels decreased by 70% (P < 0.001). Mean plasma and serum viscosity levels decreased by 0.082 mPa/s (P = 0.003) and 0.086 mPa/s (P = 0.013), respectively. Fibrinogen levels did not change significantly. Triglyceride-lowering therapy reduced plasma and serum viscosity without changes in fibrinogen levels. Since serum samples are deplete of fibrinogen, the serum viscosity reduction observed is corroborative evidence for an independent effect of triglyceride-lowering therapy on plasma viscosity. This observation provides a physiological rationale for triglyceride-lowering therapy in patients at risk for atherosclerotic vascular disease, the chylomicronemia syndrome and pancreatitis.