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 African-Americans 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 Study cohort members. Previously established AF risk factors, namely high blood pressure, elevated body mass index, diabetes, cigarette smoking and prior cardiac disease were categorized into ‘optimal’, ‘borderline’ and ‘elevated’ levels. Based on their risk factor levels, individuals were classified into one of these three groups. The population attributable fraction of AF due to having a non-optimal risk profile was estimated separately for African-American 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 African-American women (7.45 and 3.67 per 1000 person-years, respectively). The overall prevalence of an optimal risk profile was 5.4% but this varied according to race and gender: 10% in white women versus 1.6% in African-American men. Overall, 56.5% of AF cases could be explained by having ≥ 1 elevated risk factors, of which elevated blood pressure was the most important contributor. Conclusions 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.

Background Chronic kidney disease (CKD) is associated with the incidence of cardiovascular disease. CKD may also increase the risk of atrial fibrillation (AF), but existing studies have reported inconsistent results. Methods and Results We estimated cystatin C-based glomerular filtration rate (eGFRcys) and measured urinary albumin-creatinine ratio (ACR) in 10,328 men and women free of AF from the Atherosclerosis Risk in Communities (ARIC) Study in 1996–98. Incidence of AF was ascertained through the end of 2007. During a median follow-up of 10.1 years, we identified 788 incident AF cases. Compared to individuals with eGFRcys ≥90 mL/min/1.73 m2, multivariable hazard ratios (HR) and 95% confidence intervals (CI) of AF were 1.3 (1.1–1.6), 1.6 (1.3–2.1), and 3.2 (2.0–5.0) (p for trend <0.0001) in those with eGFRcys of 60–89, 30–59 and 15–29 mL/min/1.73 m2, respectively. Similarly, presence of macroalbuminuria (ACR ≥300 mg/g, HR 3.2, 95% CI 2.3–4.5) and microalbuminuria (ACR 30–299 mg/g, HR 2.0, 95% CI 1.6–2.4) were associated with higher AF risk compared to those with ACR <30 mg/g. Risk of AF was particularly elevated in those with both low eGFRcys and macroalbuminuria (HR 13.1, 95% CI 6.0–28.6, comparing individuals with ACR≥300 mg/g and eGFRcys 15–29 vs. ACR<30 mg/g and eGFRcys ≥90 mL/min/1.73 m2). Conclusion In this large population-based study, reduced kidney function and presence of albuminuria were strongly associated with the incidence of AF independently of other risk factors.

Objective Type 2 diabetes has been inconsistently associated with risk of atrial fibrillation (AF) in previous studies that have frequently been beset by methodological challenges. Design Prospective cohort study. Setting The Atherosclerosis Risk in Communities Study. Participants Detailed medical histories were obtained on 13025 participants. Individuals were categorized as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990–92). Main Outcome Measures Diagnoses of incident AF were obtained through 2007. Associations between type 2 diabetes and markers of glucose homeostasis with the incidence of AF were estimated using Cox proportional hazards models after adjusting for possible confounders. Results Type 2 diabetes was associated with a significant increase in risk of AF (HR 1.35, 95% confidence interval [CI]: 1.14–1.60) after adjustment for confounders. There was no indication that individuals with pre-diabetes or those with undiagnosed diabetes were at increased risk of AF compared to those without diabetes. We observed a positive linear association between HbA1c and risk of AF in those with and without diabetes: 1.13 (1.07–1.20) and 1.05 (0.96–1.15) per 1% point increase, respectively. There was no association between fasting glucose or insulin (p>0.05) in those without diabetes but a significant association with fasting glucose in those with the condition (p=0.0002). Results were similar in whites and African Americans. Conclusions Diabetes, HbA1c level and poor glycemic control are independently associated with increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation.

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 (ARIC) study. Fasting HDL cholesterol (HDLc), LDL cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987–89) and each of three follow-up visits. 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 ARIC participants attending visit 2 (1990–92), 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 (HR) and 95% confidence intervals (CI) of AF associated with a one standard deviation increase in lipid levels were: 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 to those not on medications, while those taking statins had an adjusted HR of 0.91 (0.66–1.25) compared to those taking other lipid lowering mediations. Conclusions Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. HDLc and triglycerides, however, were not independently associated with AF incidence. No association was found between the use of lipid lowering medications and incident AF.

Background It has recently been reported that atrial fibrillation [AF] is associated with an increased risk of myocardial infarction [MI]. However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with type of MI [ST elevation MI (STEMI) vs. non-ST elevation MI [NSTEMI] might shed light on the potential mechanisms. Methods and Results We examined the association between AF and incident MI in 14,462 participants [mean age 54 years, 56% women, 26% African Americans] from the Atherosclerosis Risk in Communities study who were free of coronary heart disease at baseline [1987–1989] with follow-up through December 31, 2010. AF cases were identified from study visits electrocardiogram and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow up of 21.6 years, 1374 MI events occurred [829 NSTEMI, 249 STEMI, 296 unclassifiable]. In a multivariable adjusted model, AF [n=1545] as a time-varying variable was associated with a 63% increased risk of MI [HR (95% CI):1.63(1.32–2.02)]. However, AF was associated with NSTEMI [HR (95% CI): 1.80(1.39–2.31)] but not STEMI [HR (95% CI): 0.49(0.18–1.34)]; p-value for hazard ratios comparison=0.004. Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men [interaction p-value<0.01 for both]. Conclusions AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI.

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.

Background and Purpose The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans. Methods We analyzed data from 935 stroke-free participants (mean age±SD, 61.5±4.3 years; 62% women; and 51% black) from 1993–1995 through 2004–2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based prospective cohort study. Cognitive testing (including the Digit Symbol Substitution [DSS] and the Word Fluency [WF] test) was performed in 1993–1995, 1996–1998, and 2004–2006, and brain MRI scans in 1993–1995 and 2004–2006. Results During follow-up, there were 48 incident AF events. Incident AF was associated with greater annual average rate of decline in DSS (−0.77; 95% CI, −1.55 to 0.01; P=0.054) and WF (−0.80; 95% CI, −1.60 to −0.01; P=0.048). Among participants without SCIs on brain MRI scans, incident AF was not associated with cognitive decline. In contrast, incident AF was associated with greater annual average rate of decline in WF (−2.65; 95% CI, −4.26 to −1.03; P=0.002) among participants with prevalent SCIs in 1993–1995. Among participants who developed SCIs during follow-up, incident AF was associated with a greater annual average rate of decline in DSS (−1.51; 95% CI, −3.02 to −0.01; P=0.049). Conclusions The association of incident AF with cognitive decline in stroke-free individuals can be explained by the presence or development of SCIs, raising the possibility of anticoagulation as a strategy to prevent cognitive decline in AF.

It is generally accepted that preeclampsia results from reduction in perfusion to the uteroplacental unit leading to maternal hypertension and fetal growth restriction. Placental insufficiency creates an environment of fetal undernutriton, predisposing the fetus to the development of adult disease. In this study, we characterized the development and perpetuation of hypertension in two generations of male and female offspring subjected to an environment of fetal undernutrition via reduced uteroplacental perfusion pressure. Further, we examined vascular responses of resistance arteries in these animals to determine the influence of placental insufficiency on the development and perpetuation of hypertension. Experimental dams underwent a surgical procedure to reduce uteroplacental perfusion pressure, with resulting offspring comprising the first generation (F1). One male and one female from each of the F1 experimental litters served as breeders of the second generation (F2). Weekly systolic blood pressure measurements were obtained from 4 to 24 wk in control, F1, and F2 offspring. Vascular responsiveness to the vasoconstrictors phenylephrine and potassium chloride and the vasorelaxants acetylcholine and sodium nitroprusside was determined in the three offspring groups at 6, 9, and 12 wk of age. Our findings indicate that placental insufficiency during a critical developmental window in late gestation leads to hypertension in juvenile Sprague-Dawley rat offspring and is perpetuated in a second generation of offspring in a gender-specific manner. Further, exposure to placental insufficiency during late gestation leads to developmental alterations characterized by vascular hyperresponsiveness, perpetuated to a second generation of offspring in the absence of persistent environmental stimuli, contributing to hypertension.