Is self-reported "moderate" drinking in the cardiovascular benefit range associated with alcoholic behavior? A population based study.

This article aims at identifying a threshold number of drinks per day beyond which there is a high risk of developing alcoholic behavior that would enable physicians to more confidently support the use of alcohol for cardiovascular risk prevention. In a randomly selected, population-based sample of 2,042 adults 45 years or older, we graded alcohol drinking behavior using the Self-Administered Alcoholism Screening Test, quantified alcohol amount by questionnaire, and assessed the prevalence of cardiovascular disease (coronary, peripheral, or cerebrovascular disease) by medical record review. Although optimal alcohol use (< or = 2 drinks/day) was associated with reduced odds of cardiovascular disease, 43% of alcoholics and 82% of problem drinkers reported alcohol use in the optimal range as well. The association of alcohol use in the optimal range with alcohol-related behavioral problems supports the reluctance in physicians from recommending alcohol use for cardiovascular benefit, not withstanding the underreporting of alcohol use by alcoholics.

Echocardiographic characteristics of electrocardiographically unrecognized myocardial infarctions in a community population.

Unrecognized myocardial infarction (UMI) as diagnosed by surveillance electrocardiography has been shown to carry the same poor prognosis as recognized myocardial infarction (RMI). The echocardiographic characteristics of UMI have never been studied before. Due to a similar prognosis, we hypothesized that UMI and RMI would exhibit similar degrees of echocardiographic ventricular dysfunction. We studied a random community cohort of 2,042 adults who were > or =45 years of age in a cross-sectional setting in Olmsted County, Minnesota. RMI was diagnosed by review of medical records and UMI was diagnosed if the electrocardiogram met MI criteria without a previous MI recorded in the medical record. All subjects underwent transthoracic echocardiography. We identified 80 patients who had UMI and 101 who had RMI. In bivariate analyses, a stepwise increase in echocardiographic abnormalities was observed from participants who had no MI to UMI to RMI: respective mean ejection fractions were 63%, 61%, and 55; prevalences in left ventricular enlargement were 13%, 22%, and 52%; mean left ventricular mass indexes were 98, 103, and 118 g/m(2); prevalences in regional wall motion abnormality were 2%, 13%, and 42%; and prevalences in diastolic dysfunction were 25%, 56%, and 65% (p for trend <0.0001 for all comparisons). After adjusting for standard coronary risk factors, patients who had UMI continued to exhibit significant abnormalities in systolic dysfunction, diastolic dysfunction, and regional wall motion abnormality, although to a lesser extent than patients who had RMI. In conclusion, patients who have UMI manifest structural abnormalities more commonly than do patients who have no MI but less commonly than do those who have RMI. The similar prognosis after UMI and RMI cannot be explained by comparable degrees of ventricular damage.

Differential effect of experimental hypertension and hypercholesterolemia on adventitial remodeling.

OBJECTIVE: Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage. METHOD AND RESULTS: Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5+/-106 versus 38.6+/-14 and 37.2+/-6.8 mg/dL; P<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3+/-21 versus 107.4+/-8.9 and 109.4+/-7.8 mm Hg; P<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03+/-0.32 versus 0.95+/-0.29 and 1.01+/-0.09; P<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4+/-1.0 versus 1.9+/-0.3 and 2.0+/-1.2; P<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC. CONCLUSIONS: The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them. Intima-media remodeling is well-described in coronary artery disease in contrast to adventitial remodeling. Results of the current study on coronary arteries of pigs, randomized to 12 weeks of normal diet (N), hypercholesterolemic diet (HC), or renovascular hypertensive (HT), indicate that adventitial remodeling precedes intima-media remodeling early after risk factor exposure with distinct qualitative differences.

Concurrent treatment with renin-angiotensin system blockers and acetylsalicylic acid reduces nuclear factor kappaB activation and C-reactive protein expression in human carotid artery plaques.

BACKGROUND AND PURPOSE: The local renin-angiotensin system (RAS) and cyclooxygenase-2 contribute to the activation of nuclear factor kappaB (NFkappaB) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NFkappaB and CRP within atherosclerotic plaques. METHODS: Patients undergoing carotid endarterectomy were divided into groups according to treatment (RASb-acetylsalicylic acid [ASA], ASA, RASb, and control). The expression of NFkappaB, CRP, and CD40L was analyzed through Western blots in the obtained plaques. RESULTS: Plaques from patients treated with the combination of RASb and ASA showed lower expression of NFkappaB (25.4+/-9.8 densitometric units [DU]) than those of the control group (57.6+/-13.2 DU, P=0.03) as well as lower expression of CRP (20.9+/-9.6 DU) than those of the other treatment groups (ASA 86.1+/-13 DU, RASb 88.4+/-31 DU, controls 67.8+/-18.6, P=0.004). A negative expression of NFkappaB was associated with a reduced incidence of symptoms compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031). CONCLUSIONS: The combined treatment with RASb and ASA decreases the expression of inflammatory markers in atherosclerosis in humans. This study supports the role of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.

C-reactive protein relaxes human vessels in vitro.

OBJECTIVE: C-reactive protein (CRP) is a sensitive marker of inflammation and a prognostic marker in cardiovascular disease. Evidence suggests direct biological activities of CRP within the vascular wall. The study was designed to examine the vasoreactive effects of CRP. METHODS AND RESULTS: Human internal mammary artery rings were obtained during cardiovascular bypass surgery and suspended in an organ bath chamber. The rings were precontracted with endothelin-1, and response to cumulative concentrations of CRP was obtained. Experiments were repeated after initial incubation with 20, 40, and 60 mmol/L KCl, the potassium channel blockers BaCl, tetraethylammonium chloride, and glibenclamide, and the NO synthase inhibitor N-monomethyl-L-arginine and also after removal of the endothelium. CRP caused dose-dependent relaxation of human internal mammary artery rings, which was not affected by preincubation with N-monomethyl-L-arginine or removal of the endothelium. Maximum relaxation response to CRP (79.5+/-10%) was attenuated by KCl (2.5+/-11.5%, P<0.001), BaCl (24.5+/-7.5%, P<0.001), and tetraethylammonium chloride (34.9+/-8.25%, P<0.01) but not by glibenclamide. Conclusions- The present study demonstrates that CRP exerts an endothelium-independent vasorelaxing effect via potassium channels. Thus, the study suggests a role of CRP in the regulation of vascular tone.