A greater life expectancy has led to an increasing proportion of elderly patients. Increasing age is an important risk factor for cardiovascular disease, but the mechanism of risk is not well understood. Because thrombosis plays a key role in plaque development and the onset of acute coronary syndromes, the age-related increase in cardiovascular risk may be a result of a prothrombotic imbalance. The study aim was to examine the relation between age and thrombotic potential in the Framingham Offspring Cohort. Hemostatic factors previously associated with cardiovascular risk were measured in 3,230 patients (55% women) without evidence of cardiovascular disease who were participating in cycle 5 of the Framingham Offspring Study. The subjects were divided by age into decades. Advancing age was associated with a significant increase in fibrinogen and von Willebrand factor levels and measures of impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigens). For men, the mean fibrinogen levels were 21% higher in those >= 70 years versus those aged < 40 years (326 vs 268 mg/dl, p < 0.001 for linear trend). The mean fibrinogen levels were 15% higher in older than in younger women (330 vs 286 mg/dl, p < 0.001). The significant relations persisted after multivariate adjustment. In conclusion, advancing age is associated with elevated levels of hemostatic factors indicative of a prothrombotic state. Because these factors are also associated with endothelial dysfunction, these findings are consistent with an injurious effect of age on the endothelium. Measures to reduce thrombotic potential may be of particular value in the elderly, because they counter the prothrombotic state that develops with aging. (c) 2005 Elsevier Inc. All rights reserved.

AIMS:To evaluate the effect of diabetes mellitus and its treatment on the risk of arrhythmias among early survivors of acute myocardial infarction.RESEARCH DESIGN AND METHOD:The Onset Study was conducted in 64 US medical centres. Between August 1989 and September 1996, 3882 patients were interviewed after having an acute myocardial infarction. We used logistic regression models to examine the association of diabetes and its treatment with the risk of ventricular arrhythmia after adjustment for age, gender, hypertension, thrombolytic therapy, smoking, obesity, cardiac medicines and congestive heart failure.RESULTS:During the index hospitalization, patients with diabetes (n=814) were less likely to develop ventricular arrhythmias than patients without diabetes (6.8 vs. 13.3%, P<0.001). The risk of ventricular arrhythmia in patients treated with first generation sulphonylureas or diet alone was similar to patients without diabetes (OR=0.91; 95% CI, 0.39-2.15, and 0.76; 95% CI, 0.46-1.26, respectively). However, compared with patients without diabetes, the adjusted odds ratio (OR) for ventricular arrhythmias was lower among patients treated with insulin or patients treated with second generation sulphonylureas (OR=0.54, 95% CI 0.32-0.92; OR=0.45, 95% CI 0.27-0.75, respectively).CONCLUSIONS:Compared with patients without diabetes, the risk of ventricular arrhythmias complicating acute myocardial infarction is lower in patients with diabetes treated with second generation sulphonylureas or insulin, but not in those treated with first generation sulphonylureas or diet alone. This suggests that differences in the mechanism of action of different sulphonylureas may result in clinically relevant differences in arrhythmic risk.

We assessed educational attainment and complications during hospitalization in 3,882 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. Educational attainment had a graded, inverse association with prevalence of congestive heart failure (CHF) during hospitalization, with the lowest prevalence among patients who attended college (odds ratio 0.75; 95% confidence interval, 0.57 to 0.99; p for trend 0.02), with similar findings among men, women, whites, and blacks.

SummaryAlthough obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p<0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.

Background — Some studies have suggested that tea consumption may be associated with lower mortality among individuals with cardiovascular disease, but the effects of tea consumption on mortality after acute myocardial infarction are unknown. Methods and Results — As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1900 patients hospitalized with a confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. Trained interviewers assessed self-reported usual weekly caffeinated tea consumption during the year before infarction with a standardized questionnaire. We compared long-term mortality according to tea consumption using Cox proportional hazards regression. Of the 1900 patients, 1019 consumed no tea (nondrinkers), 615 consumed <14 cups per week (moderate tea drinkers), and 266 consumed 14 or more cups per week (heavy tea drinkers). Compared with nondrinkers, age- and sex-adjusted mortality was lower among moderate tea drinkers (hazard ratio, 0.69; 95% CI, 0.53 to 0.89) and heavy tea drinkers (hazard ratio, 0.61; 95% CI, 0.42 to 0.86). Additional adjustment for clinical and sociodemographic characteristics did not appreciably alter this association (hazard ratio, 0.72; 95% CI, 0.55 to 0.94 for moderate tea drinkers; hazard ratio, 0.56; 95% CI, 0.37 to 0.84 for heavy tea drinkers). The association of tea and mortality was similar for total and cardiovascular mortality. Conclusions — Self-reported tea consumption in the year before acute myocardial infarction is associated with lower mortality after infarction.

BACKGROUND:Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear.METHODS AND RESULTS:We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92).CONCLUSIONS:Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular spectrofluorimetry. It may also be possible to use macrophage-targeted PDT to therapeutically modify inflammatory cell-laden VPs leading to plaque stabilization and reduction of sudden cardiovascular death.

Disruption of a vulnerable atherosclerotic plaque is well-recognised as the primary cause of stroke, non-fatal myocardial infarction and sudden cardiac death. Novel therapeutic agents are being developed to stabilise such plaques. The initial evaluation of these drugs would be facilitated by the use of non-invasive imaging techniques to identify vulnerable plaque and document serial changes in plaque stability. The aim of this review is to explain the characteristics of the leading non-invasive imaging modalities and discuss their role in examining the vulnerable plaque. This knowledge will be extremely important for physicians and scientists involved in the clinical evaluation of novel agents to stabilise the vulnerable plaque.

Of the 669 women interviewed for the Determinants of Myocardial Infarction Onset Study, 11 of 21 women with ongoing menstrual cycles had the onset of acute myocardial infarction during the early follicular phase of the menstrual cycle, corresponding to a threefold higher risk. In younger women at otherwise relatively low risk, the early portion of the menstrual cycle appears to be associated with particular susceptibility to myocardial infarction.