Elsayed Z. Soliman

Heart Disease and Stroke Statistics—2012 Update A Report From the American Heart Association

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e3 1. About These Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e7 2. American Heart Associations 2020 Impact Goals. . . . . . . . . . . . . . . . .e10 3. Cardiovascular Diseases . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . .e21 4. Subclinical Atherosclerosis . . . . . . . . . . . . . . . . . . . . .e45 5. Coronary Heart Disease, Acute Coronary Syndrome, and Angina Pectoris . . . . . . . . .e54 6. Stroke (Cerebrovascular Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . .e68 7. High Blood Pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .e88 8. Congenital Cardiovascular Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 9. Cardiomyopathy and Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . .e102 10. Disorders …

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.

FGF23 induces left ventricular hypertrophy

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor-dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF-receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.

Common variants in KCNN3 are associated with lone atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 × 10−12), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40–1.64; P = 1.83 × 10−21). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10−8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

Genome-wide association study of PR interval

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 × 10−8. At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.

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.