Suma Konety

Meta-analysis of Cohort and Case-Control Studies of Type-2 Diabetes Mellitus and Risk of Atrial Fibrillation

Atrial fibrillation (AF) is 1 of the most clinically diagnosed cardiac disturbances but little is known about its risk factors. Previous epidemiologic studies have reported on the association between diabetes mellitus (DM) and subsequent risk of AF, with inconsistent results. The aim of this study was to conduct a meta-analysis of published studies to reliably determine the direction and magnitude of any association between DM and AF. A systematic review and meta-analysis was conducted. PubMed and EMBASE were searched to identify prospective cohort and case-control studies that had reported on the association between DM and other measurements of glucose homeostasis with incident AF by April 2010. Studies conducted in primarily high-risk populations and participants in randomized controlled trials were excluded. Seven prospective cohort studies and 4 case-control studies with information on 108,703 cases of AF in 1,686,097 subjects contributed to this analysis. The summary estimate indicated that patients with DM had an approximate 40% greater risk of AF compared to unaffected patients (relative risk [RR] 1.39, 95% confidence interval [CI] 1.10 to 1.75, p for heterogeneity <0.001). After correcting for publication bias, the RR was 1.34 (1.07 to 1.68). Studies that had adjusted for multiple risk factors reported a smaller effect estimate compared to age-adjusted studies (RR 1.24, 95% CI 1.06 to 1.44, vs 1.70, 1.29 to 2.22, p for heterogeneity = 0.053). The population-attributable fraction of AF owing to DM was 2.5% (95% CI 0.1 to 3.9). In conclusion, DM is associated with an increased risk of subsequent AF but the mechanisms that may underpin the relation between DM and AF remain speculative.

Absolute and Attributable Risks of Atrial Fibrillation in Relation to Optimal and Borderline Risk Factors The Atherosclerosis Risk in Communities (ARIC) Study

Background— Atrial fibrillation (AF) is an important risk factor for stroke and overall mortality, but information about the preventable burden of AF is lacking. The aim of this study was to determine what proportion of the burden of AF in blacks and whites could theoretically be avoided by the maintenance of an optimal risk profile. Methods and Results— This study included 14 598 middle-aged Atherosclerosis Risk in Communities (ARIC) Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes mellitus, cigarette smoking, and prior cardiac disease, were categorized into optimal, borderline, and elevated levels. On the basis of their risk factor levels, individuals were classified into 1 of these 3 groups. The population-attributable fraction of AF resulting from having a nonoptimal risk profile was estimated separately for black and white men and women. During a mean follow-up of 17.1 years, 1520 cases of incident AF were identified. The age-adjusted incidence rates were highest in white men and lowest in black women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but varied according to race and gender: 10% in white women versus 1.6% in black men. Overall, 56.5% of AF cases could be explained by having ≥1 borderline or elevated risk factors, of which elevated blood pressure was the most important contributor. Conclusion— As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels.

Atrial Fibrillation and the Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

BACKGROUND It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts. METHODS In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2% women; and 26.6% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, ≥65 years; 58.2% women; and 15.4% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors. RESULTS In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively. CONCLUSIONS Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.

Shared Risk Factors in Cardiovascular Disease and Cancer

Cardiovascular disease (CVD) and cancer are the 2 leading causes of death worldwide. Although commonly thought of as 2 separate disease entities, CVD and cancer possess various similarities and possible interactions, including a number of similar risk factors (eg, obesity, diabetes mellitus), suggesting a shared biology for which there is emerging evidence. Although chronic inflammation is an indispensable feature of the pathogenesis and progression of both CVD and cancer, additional mechanisms can be found at their intersection. Therapeutic advances, despite improving longevity, have increased the overlap between these diseases, with millions of cancer survivors now at risk of developing CVD. Cardiac risk factors have a major impact on subsequent treatment-related cardiotoxicity. In this review, we explore the risk factors common to both CVD and cancer, highlighting the major epidemiological studies and potential biological mechanisms that account for them.

Patient and Hospital Differences Underlying Racial Variation in Outcomes After Coronary Artery Bypass Graft Surgery

Background—Few studies have examined the association of race and outcomes after coronary artery bypass graft (CABG) surgery while controlling for both patient and hospital effects. Methods and Results—We retrospectively analyzed data on a cohort of 566 785 white and 24 354 black Medicare beneficiaries 65 years old and older undergoing CABG in 1091 US hospitals from 1997 to 2000. Mortality and repeat revascularization rates were examined after sequential adjustment for patient and hospital differences by use of generalized estimating equations. Unadjusted mortality was higher (P<0.001) in black than in white patients at 30 (6.4% versus 5.2%), 90 (8.3% versus 6.6%), and 365 days (13.5% versus 9.8%) after surgery. Black patients were more likely (P<0.001) to undergo CABG at hospitals with the highest mortality (56% versus 47%) and at hospitals in the lowest volume quintile (24% versus 20%). Adjusted only for patient characteristics, mortality was 8%, 11%, and 25% higher in black patients at 30, 90, and 365 days. After adjustment for hospital effects, 30 and 90 day mortality was similar but 17% higher in black patients at 365 days. Racial differences in mortality were greater in men than in women. On adjustment for patient and hospital effects, repeat revascularization rates were similar in black and white patients. Conclusions—Racial disparities in CABG outcomes are sensitive to the effects of sex and duration of postsurgical follow-up. The increasing disparity in outcomes as follow-up increased is consistent with the hypothesis that black patients have less access to secondary prevention and rehabilitation services after surgery.

Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: The atherosclerosis risk in communities study

Background—Heart failure is an important public health concern, particularly among persons >65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. Methods and Results—The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute–sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. Conclusions—We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

Blood lipid levels, lipid-lowering medications, and the incidence of atrial fibrillation: the atherosclerosis risk in communities study.

Background— Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid-lowering medication use with AF risk. Methods and Results— We analyzed 13 969 participants (25% African American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities study. Fasting high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987–1989) and each of 3 follow-up visits. The incidence of AF was ascertained through 2007. The association of the use of statins and other lipid-lowering medications with AF was estimated in 13 044 Atherosclerosis Risk in Communities participants attending visit 2 (1990–1992), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years, there were 1433 incident AF cases. Multivariable hazard ratios (HRs) and 95% CIs of AF associated with a 1-SD increase in lipid levels were as follows: HDLc, 0.97 (0.91–1.04); LDLc, 0.90 (0.85–0.96); total cholesterol, 0.89 (0.84–0.95); and triglycerides, 1.00 (0.96–1.04). Participants taking lipid-lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82–1.13) compared with those not taking medications, whereas those taking statins had an adjusted HR of 0.91 (0.66–1.25) compared with those taking other lipid-lowering medications. Conclusions— Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. However, HDLc and triglycerides were not independently associated with AF incidence. No association was found between the use of lipid-lowering medications and incident AF.

Obesity related risk of sudden cardiac death in the atherosclerosis risk in communities study

Objective To examine the association of body mass index (BMI), waist circumference (WC) and waist hip ratio (WHR) with sudden cardiac death (SCD) in community dwelling individuals. Methods Data from a multicentre, prospective, cohort study of 14 941 men and women (African American, and white), aged 45–64 years, participating in the Atherosclerosis Risk in Communities study was analysed. Obesity measures were assessed at baseline (1987–1989). SCD was adjudicated by a committee. Results At enrolment mean±SD age of the participants was 54±6 years (55% female; 26% African American). During 12.6±2.5 years of follow-up, 253 SCD occurred (incidence rate 1.34/100 person-years). The association between obesity and SCD differed by smoking status (interaction p≤0.01). In models adjusting for age, sex, race, study centre and education level, SCD risk was positively associated (p<0.001) with BMI, WC and WHR in non-smokers, but not in smokers. WHR was more strongly associated with SCD in non-smokers than was BMI or WC (HR per SD increment (95% CI) 2.00 (1.65 to 2.42); 1.34 (1.15 to 1.56) and 1.49 (1.28 to 1.74), respectively). After adjustment for potential mediators (hypertension, diabetes, lipid profile, prevalent coronary heart disease, heart failure, and LV hypertrophy), non-smokers in the highest WHR category (>0.95 in women; >1.01 in men) had double the risk of SCD (HR 2.03, 95% CI 1.19 to 3.46; incidence rate 1.43/1000 person-years) versus those with normal WHR. Conclusions General obesity is associated with increased risk of SCD in middle-aged, non-smoking individuals, mediated by traditional cardiovascular risk factors. Central obesity, however, is independently associated with SCD by pathways that remain to be elucidated.

Absolute and Attributable Risks of Atrial Fibrillation in Relation to Optimal and Borderline Risk Factors

Background— Atrial fibrillation (AF) is an important risk factor for stroke and overall mortality, but information about the preventable burden of AF is lacking. The aim of this study was to determine what proportion of the burden of AF in blacks and whites could theoretically be avoided by the maintenance of an optimal risk profile. Methods and Results— This study included 14 598 middle-aged Atherosclerosis Risk in Communities (ARIC) Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes mellitus, cigarette smoking, and prior cardiac disease, were categorized into optimal, borderline, and elevated levels. On the basis of their risk factor levels, individuals were classified into 1 of these 3 groups. The population-attributable fraction of AF resulting from having a nonoptimal risk profile was estimated separately for black and white men and women. During a mean follow-up of 17.1 years, 1520 cases of incident AF were identified. The age-adjusted incidence rates were highest in white men and lowest in black women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but varied according to race and gender: 10% in white women versus 1.6% in black men. Overall, 56.5% of AF cases could be explained by having ≥1 borderline or elevated risk factors, of which elevated blood pressure was the most important contributor. Conclusion— As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels.

Development and Validation of a Sudden Cardiac Death Prediction Model for the General Population

Background: Most sudden cardiac death (SCD) events occur in the general population among persons who do not have any prior history of clinical heart disease. We sought to develop a predictive model of SCD among US adults. Methods: We evaluated a series of demographic, clinical, laboratory, electrocardiographic, and echocardiographic measures in participants in the ARIC study (Atherosclerosis Risk in Communities) (n=13 677) and the CHS (Cardiovascular Health Study) (n=4207) who were free of baseline cardiovascular disease. Our initial objective was to derive a SCD prediction model using the ARIC cohort and validate it in CHS. Independent risk factors for SCD were first identified in the ARIC cohort to derive a 10-year risk model of SCD. We compared the prediction of SCD with non-SCD and all-cause mortality in both the derivation and validation cohorts. Furthermore, we evaluated whether the SCD prediction equation was better at predicting SCD than the 2013 American College of Cardiology/American Heart Association Cardiovascular Disease Pooled Cohort risk equation. Results: There were a total of 345 adjudicated SCD events in our analyses, and the 12 independent risk factors in the ARIC study included age, male sex, black race, current smoking, systolic blood pressure, use of antihypertensive medication, diabetes mellitus, serum potassium, serum albumin, high-density lipoprotein, estimated glomerular filtration rate, and QTc interval. During a 10-year follow-up period, a model combining these risk factors showed good to excellent discrimination for SCD risk (c-statistic 0.820 in ARIC and 0.745 in CHS). The SCD prediction model was slightly better in predicting SCD than the 2013 American College of Cardiology/American Heart Association Pooled Cohort risk equations (c-statistic 0.808 in ARIC and 0.743 in CHS). Only the SCD prediction model, however, demonstrated similar and accurate prediction for SCD using both the original, uncalibrated score and the recalibrated equation. Finally, in the echocardiographic subcohort, a left ventricular ejection fraction <50% was present in only 1.1% of participants and did not enhance SCD prediction. Conclusions: Our study is the first to derive and validate a generalizable risk score that provides well-calibrated, absolute risk estimates across different risk strata in an adult population of white and black participants without a clinical diagnosis of cardiovascular disease.