Amino-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein as Predictors of Sudden Cardiac Death Among Women

Abstract

Background-Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease. Methods and Results-In a prospective, nested, case-control analysis within the 121 700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratioϭ2.37 for comparison of the highest and lowest quartile; P for trendϭ0.05) but not for high-sensitivity C-reactive protein (P for trendϭ0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age-and fasting-adjusted models (P for linear trendϭ0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD incrementϭ1.49; 95% confidence interval, 1.09 to 2.05; Pϭ0.01) but eliminated the relationship with high-sensitivity C-reactive protein (Pϭ0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratioϭ5.68; 95% confidence interval, 1.78 to 18.2; Pϭ0.003). Conclusions-In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD.If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women.

C-Reactive Protein, Interleukin 6, Fibrinogen and Risk of Sudden Death in European Middle-Aged Men: The PRIME Study

“…11,12 So far, the inflammatory hypothesis of sudden death in the population has been evaluated in 3 United States prospective studies with mixed results. [13][14][15] In these studies, higher C-reactive protein (CRP) was predictive of sudden death in men from the Physicians' Health Study but not in women from the Nurses' Health Study. 13,14 In the Atherosclerosis Risk in Communities Study, higher fibrinogen and higher white blood cell counts were associated with sudden death.…”

“…[13][14][15] In these studies, higher C-reactive protein (CRP) was predictive of sudden death in men from the Physicians' Health Study but not in women from the Nurses' Health Study. 13,14 In the Atherosclerosis Risk in Communities Study, higher fibrinogen and higher white blood cell counts were associated with sudden death. 15 Interleukin 6 (IL-6) is the main inducer of CRP secretion by the liver, and higher IL-6 has been associated with coronary heart disease (CHD) and especially with fatal events.…”

Importance of Biomarkers for Long-Term Mortality Prediction in Acutely Dyspneic Patients

“…In acutely dyspneic patients sST2 concentrations are strongly predictive of mortality even in the context of low NT-proBNP levels, confirming the importance of sST2 in patients without HF (33,35 ). Although inflammation is a prognostically meaningful process in acute illness, it is of note that despite the association of CRP and eotaxin to adverse cardiovascular outcomes, neither had prognostic value in the context of sST2 results (22,36 ). The superiority of sST2 over CRP or eotaxin might be attributable to its incremental prognostic value as reflected in the intersection between inflammation and cardiovascular stress predicted by sST2.…”

Regulated conformation changes in C-reactive protein orchestrate its role in atherogenesis

“…For example, several epidemiological studies failed to find an independent correlation between CRP and the disease [28][29][30]. A causal involvement of CRP in CVD was recently rejected by the finding that polymorphisms in non-coding nucleotides of the CRP gene affects the basal plasma levels of CRP but does not correlate with the risk of future CVD events [13].…”