Abstract
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Newsworthy
Risk scores predict atherosclerotic lesions in young people
There is increasing awareness that atherosclerosis begins in childhood and progresses through life. The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from young people aged 15 to 34 years who died of external causes. Coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (n = 1117) and the abdominal aorta (n = 1458) were measured. Risk scores were calculated so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the coronary arteries and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 [95% confidence interval (CI) 1.14-1.22] for the coronary arteries and 1.29 (95% CI 1.23-1.35) for the abdominal aorta. The presence of abdominal aortic lesions increased the likelihood of having coronary lesions. The authors concluded that risk scores calculated from traditional coronary heart disease risk factors are a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.
McMahan CA, et al. Risk scores predict atherosclerotic lesions in young people. Arch Intern Med 2005;
Smoking is associated with advanced coronary atherosclerosis in youth
Smoking is linked to clinical outcomes in atherosclerotic disease in older adults, but evidence that smoking affects coronary atherosclerosis in young people is incomplete. The Pathobiological Determinants of Atherosclerosis in Youth Study collected arteries, blood, and other tissues from persons 15 to 34 years of age dying of external causes and autopsied in forensic laboratories. Lesions in the proximal left anterior descending coronary arteries (LAD) from 1127 subjects were graded microscopically according to the American Heart Association criteria. Among individuals with advanced lesions (Grade 4 or 5), smokers had a much greater prevalence of Grade 5 lesions than non-smokers [odds ratio 9.61, 95% confidence interval (CI) 2.34-39.57], a difference suggesting that smoking accelerates the transition from Grade 4 to Grade 5 lesions. This association occurred among both men and women, and among persons with and without other coronary heart disease risk factors. The difference in qualities of advanced lesions suggests that smoking possibly accelerates the transition from Grade 4 to Grade 5 lesions by promoting thrombosis and accretion on the intimal surface of the plaque.
Zieske AW, et al. Smoking is associated with advanced coronary atherosclerosis in youth. Atherosclerosis 2005;
Metabolic syndrome and subclinical atherosclerosis in young people
Another study in young people investigated the association of metabolic syndrome (MetS) with subclinical atherosclerosis, determined by ultrasound carotid intima-media thickness measurements, in young adults. Non-diabetic subjects from Bogalusa Heart Study, a longitudinal study of atherosclerosis in young adults, underwent B-mode ultrasonography of the carotid arteries. Of 507 subjects [39% male, mean (SD) age 32 (3) years], 67 (13%) met World Health Organization (WHO) criteria for metabolic syndrome and 65 (13%) met the National Cholesterol Education Program (NCEP) criteria for metabolic syndrome. Composite carotid intima-media thickness increased with the number of MetS components present. These results support the importance of screening and also early intervention in young people with a suspicion of metabolic syndrome.
Tzou WS, et al. Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study. J Am Coll Cardiol 2005;
Dark chocolate may be beneficial in hypertensives
Consumption of flavanol-rich dark chocolate has been shown to decrease blood pressure and insulin resistance in healthy subjects. A group of researchers tested the effect of dark chocolate on 24-h ambulatory blood pressure, flow-mediated dilation and oral glucose tolerance tests in hypertensive men and women. White chocolate was selected as the control because, unlike dark chocolate, it does not contain the flavanols thought to be responsible for the apparent benefits. After a 7-day chocolate-free run-in phase, 20 never-treated hypertensives (10 males; aged 43.7 ± 7.8 years) were randomized to receive either 100 g per day dark chocolate (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Ambulatory systolic blood pressure decreased after dark chocolate by almost 12 mmHg and diastolic blood pressure by 8.5 ± 5.0 mmHg (P < 0.0001). White chocolate had no effect. In addition, dark, but not white, chocolate decreased serum low-density lipoprotein (LDL) cholesterol, improved flow-mediated dilation and ameliorated insulin sensitivity. These results suggest that, while balancing total calorie intake, flavanols from cocoa products may provide some cardiovascular benefit if included as part of a healthy diet.
Grassi D, et al. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 2005;
Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis
Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.
The authors conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, non-fatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.
After 4 weeks of treatment, the median level of low-density lipoprotein (LDL) cholesterol was reduced by 42% among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3%. During a median follow-up period of 4 years, 469 patients (37%) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo [relative risk, 0.92; 95% confidence interval (CI) 0.77-1.10; P = 0.37]. Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95% CI 1.05-3.93; P =0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95% CI 0.68-0.99; P = 0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95% CI 0.81-1.55; P = 0.49) or total mortality (relative risk, 0.93; 95% CI 0.79-1.08; P = 0.33).
Thus, atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, non-fatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.
Wanner C, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;
Perioperative beta-blocker therapy
Despite limited evidence from randomized trials, perioperative treatment with beta-blockers is now widely advocated. This study assessed the use of perioperative beta-blockers and their association with in-hospital mortality in routine clinical practice.
The authors conducted a retrospective cohort study of patients 18 years of age or older who underwent major non-cardiac surgery in 2000 and 2001 at 329 hospitals throughout the United States. Propensity-score matching was used to adjust for differences between patients who received perioperative beta-blockers and those who did not receive such therapy.
Of 782969 patients, 663 635 (85%) had no recorded contraindications to beta-blockers, 122 338 of whom (18%) received such treatment during the first two hospital days, including 14% of patients with a Revised Cardiac Risk Index (RCRI) score of 0, and 44% with a score of 4 or higher. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk; among the 580 665 patients with an RCRI score of 0 or 1, treatment was associated with no benefit and possible harm, whereas among the patients with an RCRI score of 2, 3, or 4 or more, the adjusted odds ratios for death in the hospital were 0.88 [95% confidence interval (CI) 0.80-0.98], 0.71 (95% CI 0.63-0.80), and 0.58 (95% CI 0.50-0.67), respectively.
Therefore, perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk, but not low-risk, patients undergoing major non-cardiac surgery. Patient safety may be enhanced by increasing the use of beta-blockers in high-risk patients.
Lindenauer PK, et al. Perioperative beta-blocker therapy and mortality after major non-cardiac surgery. N Engl J Med 2005;
Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization
Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents.
The authors conducted a randomized, controlled, single-blind trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (death from cardiac causes, myocardial infarction, and ischemia-driven revascularization of the target lesion) by 9 months. Follow-up angiography was completed in 540 of 1012 patients (53.4%).
The two groups had similar baseline clinical and angiographic characteristics. The rate of major adverse cardiac events at 9 months was 6.2% in the sirolimus-stent group and 10.8% in the paclitaxel-stent group [hazard ratio, 0.56; 95% confidence interval (CI) 0.36-0.86; P = 0.009]. The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group (4.8 vs. 8.3%; hazard ratio, 0.56; 95% CI 0.34-0.93; P = 0.03). Rates of death from cardiac causes were 0.6% in the sirolimus-stent group and 1.6% in the paclitaxel-stent group (P = 0.15); the rates of myocardial infarction were 2.8 and 3.5%, respectively (P = 0.49); and the rates of angiographic restenosis were 6.6 and 11.7%, respectively (P = 0.02).
As compared with paclitaxel-eluting stents, the use of sirolimus-eluting stents results in fewer major adverse cardiac events, primarily by decreasing the rates of clinical and angiographic restenosis.
Windecker S, et al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med 2005;
Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients
Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis. It is not known whether there are differences in the effectiveness of currently approved drug-eluting stents in the high-risk subgroup of patients with diabetes mellitus.
This study enrolled 250 patients with diabetes and coronary artery disease: 125 were randomly assigned to receive paclitaxel-eluting stents, and 125 to receive sirolimus-eluting stents. The primary end point was in-segment late luminal loss. Secondary end points were angiographic restenosis (defined as in-segment stenosis of at least 50% at follow-up angiography) and the need for revascularization of the target lesion during a 9-month follow-up period. The study was designed to show non-inferiority of the paclitaxel stent as compared with the sirolimus stent, defined as a difference in the extent of in-segment late luminal loss of no more than 0.16 mm.
The extent of in-segment late luminal loss was 0.24 mm (95% confidence interval, 0.09-0.39) greater in the paclitaxel-stent group than in the sirolimus-stent group (P = 0.002). In-segment restenosis was identified on follow-up angiography in 16.5% of the patients in the paclitaxel-stent group and 6.9% of the patients in the sirolimus-stent group (P =0.03). Target-lesion revascularization was performed in 12.0% of the patients in the paclitaxel-stent group and 6.4% of the patients in the sirolimus-stent group (P = 0.13).
In patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss, as compared with use of the paclitaxel-eluting stent, suggesting a reduced risk of restenosis.
Dibra A, et al. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. N Engl J Med 2005;