Sunil K. Agarwal

Type 2 diabetes, glucose homeostasis and incident atrial fibrillation: the Atherosclerosis Risk in Communities study

Background Type 2 diabetes has been inconsistently associated with the 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 (ARIC) study. Participants Detailed medical histories were obtained from 13 025 participants. Individuals were categorised as having no diabetes, pre-diabetes or diabetes based on the 2010 American Diabetes Association criteria at study baseline (1990–2). Main outcome measures Diagnoses of incident AF were obtained to the end of 2007. Associations between type 2 diabetes and markers of glucose homeostasis and 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 the risk of AF (HR 1.35, 95% CI 1.14 to 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 with those without diabetes. A positive linear association was observed between HbA1c and the risk of AF in those with and without diabetes (HR 1.13, 95% CI 1.07 to 1.20) and HR 1.05, 95% CI 0.96 to 1.15 per 1% point increase, respectively). There was no association between fasting glucose or insulin in those without diabetes, but a significant association with fasting glucose was found in those with the condition. The results were similar in white subjects and African-Americans. Conclusions Diabetes, HbA1c level and poor glycaemic control are independently associated with an increased risk of AF, but the underlying mechanisms governing the relationship are unknown and warrant further investigation.

Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) Study

OBJECTIVES To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African Americans. BACKGROUND African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African Americans have not been previously published. METHODS We studied the incidence of AF in the Atherosclerosis Risk in Communities (ARIC) study, which has followed up 15,792 men and women 45 to 65 years of age at baseline from 4 communities in the United States since 1987. Atrial fibrillation cases were identified from electrocardiograms conducted at baseline and 3 follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African Americans, 889 in whites). RESULTS Crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1,000 persons per year in white men, white women, African-American men, and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% CI: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at 80 years of age was 21% in white men, 17% in white women, and 11% in African-American men and women. CONCLUSION In this population-based cohort, African Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before 80 years of age.

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 × 10−7). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 × 10−11; combined RR = 1.25; combined P = 1.8 × 10−15).

Simple risk model predicts incidence of atrial fibrillation in a racially and geographically diverse population: the CHARGE-AF consortium

Background Tools for the prediction of atrial fibrillation (AF) may identify high‐risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Methods and Results Individual‐level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment—Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5‐year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C‐statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C‐statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, −0.0032; 95% CI, −0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C‐statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C‐statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. Conclusion A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.

Chronic Kidney Disease Is Associated With the Incidence of Atrial Fibrillation The Atherosclerosis Risk in Communities (ARIC) Study

Background— Chronic kidney disease is associated with the incidence of cardiovascular disease. Chronic kidney disease 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-to-creatinine ratio (ACR) in 10 328 men and women free of AF from the Atherosclerosis Risk in Communities (ARIC) Study in 1996 to 1998. 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 with individuals with eGFRcys ≥90 mL · min−1 · 1.73 m−2, multivariable hazard ratios and 95% confidence intervals (CIs) of AF were 1.3 (95% CI, 1.1 to 1.6), 1.6 (95% CI, 1.3 to 2.1), and 3.2 (95% CI, 2.0 to 5.0; P for trend <0.0001) in those with eGFRcys of 60 to 89, 30 to 59, and 15 to 29 mL · min−1 · 1.73 m−2, respectively. Similarly, the presence of macroalbuminuria (ACR ≥300 mg/g; hazard ratio, 3.2; 95% CI, 2.3 to 4.5) and microalbuminuria (ACR, 30 to 299 mg/g; hazard ratio, 2.0; 95% CI, 1.6 to 2.4) was associated with higher AF risk compared with those with ACR <30 mg/g. Risk of AF was particularly elevated in those with both low eGFRcys and macroalbuminuria (hazard ratio, 13.1; 95% CI, 6.0 to 28.6, comparing individuals with ACR ≥300 mg/g and eGFRcys of 15 to 29 mL · min−1 · 1.73 m−2 and those with ACR <30 mg/g and eGFRcys ≥90 mL · min−1 · 1.73 m−2). 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. # Clinical Perspective {#article-title-43}Background— Chronic kidney disease is associated with the incidence of cardiovascular disease. Chronic kidney disease 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-to-creatinine ratio (ACR) in 10 328 men and women free of AF from the Atherosclerosis Risk in Communities (ARIC) Study in 1996 to 1998. 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 with individuals with eGFRcys ≥90 mL · min−1 · 1.73 m−2, multivariable hazard ratios and 95% confidence intervals (CIs) of AF were 1.3 (95% CI, 1.1 to 1.6), 1.6 (95% CI, 1.3 to 2.1), and 3.2 (95% CI, 2.0 to 5.0; P for trend <0.0001) in those with eGFRcys of 60 to 89, 30 to 59, and 15 to 29 mL · min−1 · 1.73 m−2, respectively. Similarly, the presence of macroalbuminuria (ACR ≥300 mg/g; hazard ratio, 3.2; 95% CI, 2.3 to 4.5) and microalbuminuria (ACR, 30 to 299 mg/g; hazard ratio, 2.0; 95% CI, 1.6 to 2.4) was associated with higher AF risk compared with those with ACR <30 mg/g. Risk of AF was particularly elevated in those with both low eGFRcys and macroalbuminuria (hazard ratio, 13.1; 95% CI, 6.0 to 28.6, comparing individuals with ACR ≥300 mg/g and eGFRcys of 15 to 29 mL · min−1 · 1.73 m−2 and those with ACR <30 mg/g and eGFRcys ≥90 mL · min−1 · 1.73 m−2). 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.

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.

A clinical risk score for atrial fibrillation in a biracial prospective cohort (from the Atherosclerosis Risk in Communities [ARIC] study).

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study; however, the applicability of this risk score, derived using data from white patients, to predict new-onset AF in nonwhites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF from risk factors commonly measured in clinical practice using 14,546 subjects from the Atherosclerosis Risk In Communities (ARIC) study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication use, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver operating characteristics curve (AUC) of a Cox regression model that included the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from the coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the Atherosclerosis Risk In Communities cohort compared favorably with the Framingham Heart Studys AF (AUC 0.68), coronary heart disease (CHD) (AUC 0.63), and hard CHD (AUC 0.59) risk scores and the Atherosclerosis Risk In Communities CHD risk score (AUC 0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score in identifying subjects at greater risk of AF.

Metabolic syndrome and incidence of atrial fibrillation among blacks and whites in the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND The metabolic syndrome (MetSyn) has been implicated in the development of atrial fibrillation (AF); however, knowledge of this association among blacks is limited. METHODS We determined the risk of incident AF through December 2005 in relation to baseline (1987-1989) MetSyn status in 15,094 participants of the Atherosclerosis Risk in Communities study. RESULTS Over a mean follow-up of 15.4 years, 1,238 incident AF events were identified. The hazard ratio (HR) for AF among individuals with, compared to those without, the MetSyn was 1.67 (95% CI 1.49-1.87), and associations did not differ by race (P for interaction = .73). The population attributable risk of AF from the MetSyn was 22%. The multivariable-adjusted HRs (95% CI) for each MetSyn component were 1.95 (1.72-2.21) (elevated blood pressure), 1.40 (1.23-1.59) (elevated waist circumference), 1.20 (1.06-1.37) (low high-density lipoprotein cholesterol), 1.16 (1.03-1.31) (impaired fasting glucose), and 0.95 (0.84-1.09) (elevated triglycerides). A monotonically increasing risk of AF with increasing number of MetSyn components was observed, with an HR of 4.40 (95% CI 3.25-5.94) for those with all 5 MetSyn components compared to those with 0 components. CONCLUSION In this large cohort, the MetSyn and most of its components were associated with a higher risk of AF in both blacks and whites. Given the high prevalence of the MetSyn, strategies to prevent its development or to control individual components may reduce the burden of AF.

Exercise Training in Patients With Heart Failure and Preserved Ejection Fraction Meta-Analysis of Randomized Control Trials

Background—Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life, and diastolic function in patients with HFPEF. Methods and Results—Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Effect of exercise training on quality of life (estimated using Minnesota living with heart failure score), and left ventricular systolic and diastolic function was also assessed. The study included 276 patients who were enrolled in 6 randomized controlled trials. In the pooled data analysis, patients with HFPEF undergoing exercise training had significantly improved CRF (mL/kg per min; weighted mean difference, 2.72; 95% confidence interval, 1.79–3.65) and quality of life (weighted mean difference, −3.97; 95% confidence interval, −7.21 to −0.72) when compared with the control group. However, no significant change was observed in the systolic function (EF−weighted mean difference, 1.26; 95% confidence interval, −0.13% to 2.66%) or diastolic function (E/A−weighted mean difference, 0.08; 95% confidence interval, −0.01 to 0.16) with exercise training in patients with HFPEF. Conclusions—Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function.

The impact of HIV/AIDS on the quality of life: a cross sectional study in north India

OBJECTIVE To determine the impact of Human Deficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) on the quality of life (QOL) on such patients in North India. DESIGN A cross sectional study. SETTING Outpatient setting and wards, Department of Medicine at a premier tertiary health care center, North India. PARTICIPANTS Sixty-eight consecutive HIV/AIDS patients attending Medicine out patient department and/or admitted to the wards of All India Institute of Medical Sciences were administered a structured questionnaire by the HIV nurse coordinator. QOL was evaluated using the WHOQOL-Bref (Hindi) instrument. ANALYSIS One way Analysis of Variance (ANOVA) was performed to find out significant difference between the clinical categories and socio-demographic variables on QOL domains. RESULTS The overall QOL mean score on a scale of 0-100 was found to be 25.8. Similarly, on the scale of 0-100 the mean scores in the four domains of QOL in descending order were social (80.9); psychological (27.5); physical (17.7) and environmental domain (11.65). There was a significant difference of quality of life in the physical domain between asymptomatic patients (14.6) and patients with AIDS (10.43) defining illnesses (p< 0.001) and asymptomatic and early symptomatic (12) patients (p=0.014). QOL in the psychological domain was significantly poorer in early symptomatic (12.1) (p< 0.05) and AIDS patients (12.4) (p< 0.006) as compared to asymptomatic individuals (14.2). A significant difference in QOL scores in the psychological domain was observed with respect to the educational status (p< 0.037) and income of patients (p< 0.048). Significantly better QOL scores in the physical (p< 0.040) and environmental domain (p< 0.017) were present with respect to the occupation of the patients. Patients with family support had better QOL scores in environmental domain. CONCLUSIONS In our study, QOL is associated with education, income, occupation, family support and clinical categories of the patients.