Prediction of ASCVD risk in general population using CV biomarkers

In an analysis of 28 cohorts, hs-cTnI, hs-cTnT, NT-proBNP, BNP, and hs-CRP were predictors of mortality and CV events. Addition of these biomarkers to conventional risk factors resulted in a better risk prediction of HF, mortality, and, to a lesser extent, ASCVD.

This summary is based on the publication of Neumann JT, Twerenbold R, Weimann J, et al. - Prognostic Value of Cardiovascular Biomarkers in the Population. JAMA. 2024 Jun 11;331(22):1898-1909. doi: 10.1001/jama.2024.5596

Introduction and methods

Background

To reduce the prevalence of ASCVD, it is important individuals at high risk of developing this disease are identified early [1,2]. Although several studies have shown the value of routinely available CV biomarkers for risk stratification [3-10], application of these biomarkers for stratifying risk in primary prevention has not become routine clinical practice. Moreover, it is unclear which of the established biomarkers is suited to predict each outcome and whether age plays a role in this.

Aim of the study

The study aim was to compare the predictive value of CV biomarkers for incident ASCVD events in the general population and elucidate their differential effects according to age.

Methods

In an individual-level analysis, data on CV biomarkers from 28 general population–based cohorts from 12 countries on 4 continents were included (total n=164,054). Study participants were apparently healthy (i.e., they did not have a history of major atherothrombotic CV events, ASCVD, or HF) and had ≥1 measurements of hs-cTnI, hs-cTnT, NT-proBNP, BNP, and/or hs-CRP during a follow-up ≥2 years. Median follow-up duration was 11.8 years (IQR: 6.2–18.0; maximum: 28.2 years).

Outcomes

The primary endpoint was the incidence of total (fatal and nonfatal) ASCVD events (defined as definite CHD event, possible or definite ischemic stroke event, coronary revascularization, CHD death, ischemic stroke death, or unclassifiable death). Secondary endpoints were all-cause mortality, HF, ischemic stroke, and MI.

Main results

Association of biomarkers with primary and secondary endpoints

• After adjustment for sex, cohort, and conventional risk factors (including age, total cholesterol levels, smoking status), all biomarkers were associated with incident ASCVD. The subdistribution HR per 1-SD change was 1.13 (95%CI: 1.11–1.16) for hs-cTnI, 1.18 (95%CI: 1.12–1.23) for hs-cTnT, 1.21 (95%CI: 1.18–1.24) for NT-proBNP, 1.14 (95%CI: 1.08–1.22) for BNP, and 1.14 (95%CI: 1.12–1.16) for hs-CRP.
• For all 5 biomarkers, the rate of ASCVD events was increased in individuals with biomarker concentrations above the median compared with those with biomarker concentrations below the median.
• The addition of each single biomarker to a base model that included the conventional risk factors was associated with a small increase in the C statistic for ASCVD events at 1, 5, and 10 years. When hs-cTnI, NT-proBNP, and hs-CRP were combined in 1 model, the C statistic increase was greatest.
• All biomarkers were also associated with increased incidences of all-cause mortality, HF, ischemic stroke, and MI, whereby the associations of the biomarkers with all-cause mortality and HF were larger than those for ASCVD. 
• Once more, addition of the biomarkers to the base model improved the C statistics for these secondary endpoints, mostly for all-cause mortality and HF.

Stratification by age

• The C statistic of the base model was substantially lower in older than younger individuals.
• Addition of the biomarkers to the base model resulted in higher absolute increases of the C statistic in older people. For example, combining hs-cTnI, NT-proBNP, and hs-CRP in 1 model improved the C statistic for 10-year incident ASCVD from 0.6323 (95%CI: 0.5945–0.6570) to 0.6602 (95%CI: 0.6224–0.6834) in individuals aged ≥65 years and from 0.812 (95%CI: 0.8021–0.8208) to 0.8194 (95%CI: 0.8089–0.8277) in those aged <65 years.
• The combination of these 3 biomarkers also increased the overall net reclassification improvement for ASCVD in individuals aged ≥65 years (0.062; 95%CI: 0.013–0.120) compared with those aged <65 years (0.028; 95%CI: 0.010–0.070).

Conclusion

This large individual-level analysis demonstrated 5 routinely available CV biomarkers (hs-cTnI, hs-cTnT, NT-proBNP, BNP, and hs-CRP) were predictors of fatal and nonfatal CV events and all-cause mortality in a global general population. Addition of these biomarkers to conventional risk factors, such as age and smoking status, resulted in a slightly better risk prediction for ASCVD and even more so for HF and all-cause mortality. The incremental value of the biomarkers was greater in individuals aged ≥65 years compared with younger people.

Find this article online at JAMA.

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