High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy

Abstract

Background: Cardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood.

Methods and results: We measured high-sensitivity cardiac troponin I (hsTnI) in 12 956 and BNP in 11 076 participants without cardiovascular disease in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial before randomization to rosuvastatin 20 mg/d or placebo. Nearly 92% of participants had detectable circulating hsTnI, and 2.9% of men and 4.1% of women had levels above proposed sex-specific reference limits of 36 and 15 ng/L, respectively. hsTnI concentrations in the highest tertile were associated with a first major cardiovascular event (adjusted hazard ratio [aHR], 2.19; 95% confidence interval, 1.56-3.06; P for trend <0.001). BNP levels in the highest tertile were also associated a first cardiovascular event (aHR, 1.94; 95% confidence interval, 1.41-2.68; P for trend <0.001). The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02). Rosuvastatin was equally effective in preventing a first cardiovascular event across categories of hsTnI (aHR range, 0.50-0.60) and BNP (aHR range, 0.42-0.67) with no statistically significant evidence of interaction (P for interaction=0.53 and 0.20, respectively).

Conclusions: In a contemporary primary prevention population, baseline cardiac troponin I and BNP were associated with the risk of vascular events and all-cause mortality. The benefits of rosuvastatin were substantial and consistent regardless of baseline hsTnI or BNP concentrations.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Keywords: hydroxymethylglutaryl-CoA reductase inhibitors; natriuretic peptide, brain; primary prevention; troponin.

Figure 1.

Cumulative incidence of a first major cardiovascular event according to baseline tertile of high-sensitivity cardiac troponin I (hsTnI tertile; A) or B-type natriuretic peptide (BNP tertile; B). A first major cardiovascular event is defined as the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) primary end point (nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, arterial revascularization, or death resulting from cardiovascular causes). The sex-specific tertile cut points for hsTnI were 3.0 and 4.6 ng/L in men and 2.6 and 3.9 ng/L in women. The sex-specific tertile cut points for BNP were 20 and 28.6 ng/L in men and 20 and 44.4 ng/L in women. For the Kaplan–Meier analysis and log-rank P values presented here, follow-up was limited to 2.5 years, when 25% and 20% of patients remained in the hsTnI and BNP analyses, respectively.

Figure 2.

Adjusted hazard ratios and 95% confidence intervals of a first major cardiovascular event for the highest vs lowest tertile of high-sensitivity cardiac troponin I (hsTnI) stratified by a number of key risk subgroups. Risk estimates are adjusted for age, sex, drug, race, hypertension, smoking, body mass index (BMI), total cholesterol, high-density lipoprotein (HDL) cholesterol, family history of coronary heart disease, and high-sensitivity C-reactive protein (hsCRP) at baseline. LDL indicates low-density lipoprotein. *Incidence rates are per 100 person-years of observation.

Figure 3.

Adjusted hazard ratios and 95% confidence intervals of a first major cardiovascular event for the highest vs lowest tertile of B-type natriuretic peptide (BNP) stratified by a number of key risk subgroups. Risk estimates for are adjusted for age, sex, drug, race, hypertension, smoking, body mass index (BMI), total cholesterol, high-density lipoprotein (HDL) cholesterol, family history of coronary heart disease, and high-sensitivity C-reactive protein (hsCRP) at baseline. LDL indicates low-density lipoprotein. *Incidence rates are per 100 person-years.

Figure 4.

Adjusted hazard ratios and 95% confidence intervals for the highest vs lowest tertile of high-sensitivity cardiac troponin I (hsTnI) for the individual components of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) composite primary end point, as well as all-cause death, coronary heart disease, and the composite of the primary end point or all-cause death. Risk estimates are adjusted for age, sex, drug, race, hypertension, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, family history of coronary heart disease, and high-sensitivity C-reactive protein at baseline. *Incidence rates are per 100 person-years. Total N=12956.

Figure 5.

Adjusted hazard ratios and 95% confidence intervals for the highest vs lowest tertile of B-type natriuretic peptide (BNP) for the individual components of the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) composite primary end point, as well as all-cause death, coronary heart disease, and the composite of the primary end point or all-cause death. Risk estimates are adjusted for age, sex, drug, race, hypertension, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, family history of coronary heart disease, and high-sensitivity C-reactive protein at baseline. *Incidence rates are per 100 person-years. Total n=11 057.