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Heart failure, a strong risk factor for atrial fibrillation (AF), is often accompanied by elevated liver transaminases. The aim of this study was to test the hypothesis that elevated transaminases are associated with the risk for incident AF in the community. A total of 3,744 participants (mean age 65 ± 10 years, 56.8% women) from the Framingham Heart Study Original and Offspring cohorts, free of clinical heart failure, were studied. Cox proportional-hazards models adjusted for standard AF risk factors (age, gender, body mass index, systolic blood pressure, electrocardiographic PR interval, antihypertensive treatment, smoking, diabetes, valvular heart disease, and alcohol consumption) were examined to investigate associations between baseline serum transaminase levels (alanine transaminase and aspartate transaminase) and the incidence of AF over up to 10 years (29,099 person-years) of follow-up. During follow-up, 383 subjects developed AF. The 2 transaminases were significantly associated with greater risk for incident AF (hazard ratio expressed per SD of natural logarithmically transformed biomarker: alanine transaminase hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.002; aspartate transaminase hazard ratio 1.12, 95% confidence interval 1.01 to 1.24, p = 0.03). The associations between transaminases and AF remained consistent after the exclusion of participants with moderate to severe alcohol consumption. However, when added to known risk factors for AF, alanine transaminase and aspartate transaminase only subtly improved the prediction of AF. In conclusion, elevated transaminase concentrations are associated with increased AF incidence. The mechanisms by which higher mean transaminase concentrations are associated with incident AF remain to be determined.

In randomized trials, longer drug-eluting stent (DES) length has been associated with adverse clinical events. We used data from the EVENT registry to examine the impact of DES length on outcomes in routine clinical practice. We identified 5,425 unselected consecutive patients from the EVENT registry who had a single vessel treated with DES for nonemergency indications from 2004 through 2007. The association between stented length and short- and long-term outcomes was analyzed in ordinal categories (15, 15 to 19, 20 to 24, and24 mm) and as a continuous variable. There were few differences in baseline characteristics across categories. At 1 year, there was a stepwise increase in major adverse cardiac events (composite of death, myocardial infarction [MI], and target lesion revascularization [TLR]) with increasing stent length (8.0%, 10.1%, 11.8%, and 14.8%, p0.001) and a similar relation with TLR (3.0%, 3.1%, 3.3%, and 5.0%, p = 0.02). After adjusting for demographic, clinical, angiographic, and treatment characteristics, longer stent length remained associated with 1-year major adverse cardiac events (adjusted hazard ratio 1.17 per 10-mm increase stent length) and TLR (hazard ratio 1.20 per 10 mm), but not with stent thrombosis. In conclusion, longer DES length is associated with increased adverse events, predominantly periprocedural MI, but also an increased rate of TLR.

The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p

Restenosis is associated with acute myocardial infarction (MI) either at presentation or related to complications of target lesion revascularization (TLR). The cumulative late effect of TLR after drug-eluting or bare metal stent placement on cardiac death or MI is uncertain. Of the 1,057 patients with one native coronary lesion randomized to a sirolimus-eluting stent or bare metal stent in the Sirolimus-Eluting Stent in De Novo Native Coronary Lesions (SIRIUS) trial, the 983 who survived free of MI for the first 30 days were evaluated for the primary outcome of cardiac death or MI for 5 years. Patients with events occurring at or after TLR were assigned to TLR group. Cox proportional hazards regression analysis with TLR as a time-dependent variable and adjustment for baseline clinical and demographic covariates was used to assess the independent effect of TLR on the primary outcome. TLR occurred in 160 patients (16.3%) and was an independent predictor of the primary end point (hazard ratio 2.8, 95% confidence interval 1.7 to 4.5). This association was significant for sirolimus-eluting stents and bare metal stents. TLR was also associated with an increased risk of subsequent stent thrombosis and nontarget vessel revascularization. Intracoronary brachytherapy in the TLR group was associated with an increased risk of cardiac death or MI. In conclusion, restenosis requiring TLR was associated with an increased risk of cardiac death or MI occurring at TLR and during the subsequent 5 years.

Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary heart disease (CHD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and coronary heart disease (CHD). We performed a prospective analysis using Cox-proportional hazards regression models in the Framingham Heart Study Original Cohort and Offspring database. This cohort included 23,376 person-exams, 3,890 (17%) of whom were identified as having corneal arcus during their physical exam. Corneal arcus was a predictor of both CVD and CHD at 4 years [hazard ratio (HR) = 2.28 and 1.99, respectively] and 8 years of follow-up (HR = 2.52 and 2.35, p0.05 for all). In conclusion, corneal arcus predicts CVD and CHD in the community-based Framingham Heart Study cohort due to the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CHD.

Higher left ventricular (LV) mass, wall thickness, and internal dimension are associated with increased heart failure (HF) risk. Whether different LV hypertrophy patterns vary with respect to rates and types of HF incidence is unclear. In this study, 4,768 Framingham Heart Study participants (mean age 50 years, 56% women) were classified into 4 mutually exclusive LV hypertrophy pattern groups (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) using American Society of Echocardiography-recommended thresholds of echocardiographic LV mass indexed to body surface area and relative wall thickness, and these groups were related to HF incidence. Whether risk for HF types (HF with reduced ejection fraction [45%] vs preserved ejection fraction [≥45%]) varied by hypertrophy pattern was then evaluated. On follow-up (mean 21 years), 458 participants (9.6%, 250 women) developed new-onset HF. The age- and gender-adjusted 20-year HF incidence increased from 6.96% in the normal left ventricle group to 8.67%, 13.38%, and 15.27% in the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups, respectively. After adjustment for co-morbidities and incident myocardial infarction, LV hypertrophy patterns were associated with higher HF incidence relative to the normal left ventricle group (p = 0.0002); eccentric hypertrophy carried the greatest risk (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.41 to 2.54), followed by concentric hypertrophy (HR 1.40, 95% CI 1.04 to 1.87). Participants with eccentric hypertrophy had a higher propensity for HF with reduced ejection fraction (HR 2.23, 95% CI 1.48 to 3.37), whereas those with concentric hypertrophy were more prone to HF with preserved ejection fraction (HR 1.66, 95% CI 1.09 to 2.51). In conclusion, in this large community-based sample, HF risk varied by LV hypertrophy pattern, with eccentric and concentric hypertrophy predisposing to HF with reduced and preserved ejection fraction, respectively.

Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased the risk of IC in adult offspring, independent of the established cardiovascular risk factors. We evaluated the Offspring Cohort Participants of the Framingham Heart Study who were ≥30 years old, cardiovascular disease free, and had both parents enrolled in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled proportional hazards regression analysis was used to examine whether the 12-year risk of incident IC in offspring participants was associated with parental IC, adjusting for age, gender, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. Of the 909 person-examinations in the parental IC history group and 5,397 person-examinations in the no-parental IC history group, there were 101 incident IC events (29 with parental IC history and 72 without a parental IC history) during follow-up. The age- and gender-adjusted 12-year cumulative incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74 to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a parental IC history. A parental history of IC significantly increased the risk of incident IC in the offspring (multivariable adjusted hazard ratio 1.81, 95% CI 1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In conclusion, IC in parents increases the risk of IC in adult offspring, independent of the established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes.

Although clopidogrel pretreatment benefits patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes, these benefits are less well established among patients undergoing elective PCI--in particular, when they are treated with the direct thrombin inhibitor, bivalirudin. We used data from the multicenter Evaluation of Drug Eluting stents and ischemic Events registry to assess the association between clopidogrel pretreatment and PCI-related complications among patients undergoing elective PCI with bivalirudin as the antithrombotic regimen. The primary end point was the composite of in-hospital death or myocardial infarction. From January 2005 and December 2007, 4,681 patients underwent elective PCI at 55 United States centers, and 1,913 (41%) received bivalirudin as the planned anticoagulant. Clopidogrel pretreatment was used in 923 patients (48%). The incidence of in-hospital death or myocardial infarction was similar among patients who did and did not receive clopidogrel pretreatment (5.5% vs 5.8%, p = 0.83). This result was unchanged in propensity-adjusted analyses (adjusted odds ratio for pretreatment 0.91, 95% confidence interval 0.60 to 1.39, p = 0.66). Also, no differences were seen in the in-hospital bleeding events (1.0% vs 1.0%, p = 0.94) or 1-year ischemic complications between the 2 treatment groups (7.5% vs 8.3%, p = 0.26). In conclusion, among unselected patients undergoing elective PCI with bivalirudin as the planned anticoagulant, clopidogrel pretreatment was common but was not associated with a reduced risk of ischemic complications.

Although previous investigations reported on the associations of lipid concentrations with left ventricular remodeling in specific subpopulations, few data exist on these associations in a community-based sample of subjects without cardiovascular disease. In this study, 3,554 Framingham Heart Study participants (mean age 47 years, 53% women) without preexisting clinical cardiovascular disease were examined, and no meaningful associations of high-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol with echocardiographic indexes of left ventricular structure were observed. In conclusion, these data do not support an independent association between lipid concentrations and left ventricular structure.