Person:

Solomon, Scott

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.

OBJECTIVES: The purpose of this study was to assess the prognostic utility of lipoprotein(a) [Lp(a)] in individuals with coronary artery disease (CAD). BACKGROUND: Data regarding an association between Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. METHODS: Plasma Lp(a) was measured in 6,708 subjects with CAD from 3 studies; data were then combined with 8 previously published studies for a total of 18,978 subjects. RESULTS: Across the 3 studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (odds ratio [OR]: 1.03 per log-transformed SD, 95% confidence interval [CI]: 0.96 to 1.11) or by quintile (Q5:Q1 OR: 1.05, 95% CI: 0.83 to 1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR: 1.40, 95% CI: 1.15 to 1.71), but with significant between-study heterogeneity (p = 0.001). When stratified on the basis of low-density lipoprotein (LDL) cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR: 1.46, 95% CI: 1.23 to 1.73, p < 0.001), whereas this relationship did not achieve statistical significance for studies with an average LDL cholesterol <130 mg/dl (OR: 1.20, 95% CI: 0.90 to 1.60, p = 0.21). CONCLUSIONS: Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.