Person:

Solomon, Scott

Background: Despite advances in prevention and treatment of cardiovascular disease, sudden cardiac death (SCD) remains a clinical challenge. Risk stratification in the general population is needed. Methods and Results: Beat‐to‐beat spatiotemporal variability in the T vector was measured as the mean angle between consecutive T‐wave vectors (mean TT′ angle) on standard 12‐lead ECGs in 14 024 participants in the Atherosclerosis Risk in Communities (ARIC) study. Subjects with left ventricular hypertrophy, atrial arrhythmias, frequent ectopy, ventricular pacing, or QRS duration ≥120 ms were excluded. The mean spatial TT′ angle was 5.21±3.55°. During a median of 14 years of follow‐up, 235 SCDs occurred (1.24 per 1000 person‐years). After adjustment for demographics, coronary heart disease risk factors, and known ECG markers for SCD, mean TT′ angle was independently associated with SCD (hazard ratio 1.089; 95% CI 1.044 to 1.137; P<0.0001). A mean TT′ angle >90th percentile (>9.57°) was associated with a 2‐fold increase in the hazard for SCD (hazard ratio 2.01; 95% CI 1.28 to 3.16; P=0.002). In a subgroup of patients with T‐vector amplitude ≥0.2 mV, the association with SCD was almost twice as strong (hazard ratio 3.92; 95% CI 1.91 to 8.05; P<0.0001). A significant interaction between mean TT′ angle and age was found: TT′ angle was associated with SCD in participants aged <55 years (hazard ratio 1.096; 95% CI 0.043 to 1.152; P<0.0001) but not in participants aged ≥55 years (Pinteraction=0.009). Conclusions: In a large, prospective, community‐based cohort of left ventricular hypertrophy–free participants, increased beat‐to‐beat spatiotemporal variability in the T vector, as assessed by increasing TT′ angle, was associated with SCD.

Background: Identifying individuals at risk for sudden cardiac death (SCD) is of critical importance. Electrocardiographic (ECG) deep terminal negativity of P wave in V1 (DTNPV1), a marker of left atrial abnormality, has been associated with increased risk of all‐cause and cardiovascular mortality. We hypothesized that DTNPV1 is associated with increased risk of sudden cardiac death (SCD). Methods and Results: This analysis included 15 375 participants (54.1±5.8 years, 45% men, 73% whites) from the Atherosclerosis Risk in Communities (ARIC) study. DTNPV1 was defined from the resting 12‐lead ECG as presence of biphasic P wave (positive/negative) in V1 with the amplitude of the terminal negative phase >100 μV, or one small box on ECG scale. After a median of 14 years of follow‐up, 311 cases of SCD occurred. In unadjusted Cox regression, DTNPV1 was associated with an 8‐fold increased risk of SCD (HR 8.21; [95%CI 5.27 to 12.79]). Stratified by race and study center, and adjusted for age, sex, coronary heart disease (CHD), and ECG risk factors, as well as atrial fibrillation (AF), stroke, CHD, and heart failure (HF) as time‐updated variables, the risk of SCD associated with DTNPV1 remained significant (2.49, [1.51–4.10]). DTNPV1 improved reclassification: additional 3.4% of individuals were appropriately reclassified into a higher SCD risk group, as compared with traditional CHD risk factors alone. In fully adjusted models DTNPV1 was associated with increased risk of non‐fatal events: AF (5.02[3.23–7.80]), CHD (2.24[1.43–3.53]), HF (1.90[1.19–3.04]), and trended towards increased risk of stroke (1.88[0.99–3.57]). Conclusion: DTNPV1 is predictive of SCD suggesting its potential utility in risk stratification in the general population.

Background: Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking. Methods and Results: We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996–1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], −43, −36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP. Conclusions: African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population.

Background: Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR). Methods and Results: Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66–90 years during 2011–2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6–87.0] g/m2 for eGFR <30 mL/min per 1.73 m2, 80.9 [95% CI, 77.3–84.6] g/m2 for eGFR 30–44 mL/min per 1.73 m2, and 80.1 [95% CI, 76.7–83.5] g/m2 for eGFR 45–59 mL/min per 1.73 m2 compared with 78.7 [95% CI, 75.3–82.1] g/m2 for eGFR 75–89 mL/min per 1.73 m2; trend P<0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m2. For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6–96.5] g/m2 for ACR ≥300 mg/g and 82.9 [95% CI, 79.4–86.3] g/m2 for ACR 30–299 mg/g compared with 77.7 [95% CI, 74.4–81.1] g/m2 for ACR <10 mg/g [trend P<0.001]; left arterial volume index, 24.9 [95% CI, 22.9–26.8] and 24.7 [95% CI, 23.4–26.1] mL/m2 compared with 23.4 [95% CI, 22.1–24.7] mL/m2, respectively [trend P=0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident. Conclusions: LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD.