This review followed PRISMA 2020 reporting guidance [17]. Because this work integrates observational epidemiology with mechanistic and therapeutic trial evidence, we used a narrative synthesis approach while maintaining systematic search and eligibility procedures.

A PRISMA 2020-compliant systematic search was conducted across the following databases: MEDLINE via PubMed, Embase (Elsevier), Web of Science Core Collection (Clarivate), and Cochrane CENTRAL. The final search was executed on February 15, 2026.

Search strategies were developed using controlled vocabulary (e.g., MeSH, Emtree) and free-text terms. The full reproducible search strings were as follows:

PubMed (MEDLINE):

(“C-Reactive Protein” [Mesh] OR “hs-CRP” OR “high-sensitivity C-reactive protein” OR inflammation) AND (“Troponin” [Mesh] OR “hs-cTn” OR “high-sensitivity troponin” OR “cardiac troponin”) AND (“subclinical myocardial injury” OR “asymptomatic” OR “primary prevention” OR “cohort” OR “longitudinal”)

Embase (Elsevier):

(“c reactive protein”/exp OR “hs crp” OR “high sensitivity c reactive protein”) AND (“troponin”/exp OR “hs ctn” OR “high sensitivity troponin”) AND (“subclinical myocardial injury” OR “asymptomatic population” OR “primary prevention”)

Web of Science:

TS = (hs-CRP OR “high-sensitivity CRP” OR inflammation) AND TS = (hs-cTn OR “high-sensitivity troponin”) AND TS = (subclinical OR asymptomatic OR cohort)

Cochrane CENTRAL:

(hs-CRP OR inflammation) AND (hs-cTn OR troponin) AND (cardiovascular OR myocardial injury)

No language restrictions were applied. Reference lists of included studies and relevant reviews were manually screened to identify additional eligible studies. [17].

Included

1) Adult cohorts measuring hs-CRP and hs-cTn and reporting associations (cross-sectional or longitudinal).

2) Stable outpatient CVD populations where baseline hs-CRP/hs-cTn relationships were evaluated.

3) Randomized trials targeting inflammation with clinical cardiovascular outcomes.

4) Mechanistic studies/reviews directly informing plausible pathways from systemic inflammation → myocardial injury/remodeling.

Excluded

1) Acute coronary syndrome populations without a stable/asymptomatic baseline context.

2) Studies lacking either inflammatory biomarkers or troponin measures.

For this review, “asymptomatic adults” were operationally defined as individuals without clinically manifest cardiovascular disease (e.g., no prior myocardial infarction, stroke, or revascularization) at baseline.

Studies including stable outpatient populations with established cardiovascular disease were not excluded but were categorized separately as secondary prevention cohorts. All results and interpretations are explicitly stratified into:

Primary prevention populations (no prior CVD).

Secondary prevention populations (established but stable CVD).

This distinction was maintained throughout data synthesis to avoid conflation of risk profiles and biological interpretations.

A total of 1248 records were identified across all databases. After removal of 312 duplicates, 936 unique records underwent title and abstract screening. Of these, 742 were excluded for irrelevance (e.g., non-human studies, acute coronary syndromes, lack of biomarker measurement). The remaining 194 articles underwent full-text review.

Of these, 128 were excluded for the following primary reasons: absence of hs-cTn measurement (n = 46), lack of hs-CRP or inflammatory marker (n = 31), non-asymptomatic or acute disease populations (n = 28), and insufficient outcome reporting (n = 23).

A total of 66 studies met inclusion criteria:

Cohort studies: n = 34

Mechanistic/translational studies: n = 18

Randomized controlled trials: n = 14

Study selection was performed independently by two reviewers, with discrepancies resolved by consensus.

We extracted study type, population, biomarkers/assays, adjustment sets, direction/magnitude of associations, and clinical outcomes. Given the heterogeneity in assays, endpoints, and reporting metrics, we performed a structured narrative synthesis emphasizing consistency, dose-response patterns, and triangulation across study designs.

Study quality was assessed using validated tools based on study design. Observational cohort studies were evaluated using the Newcastle-Ottawa Scale (NOS), assessing selection, comparability, and outcome domains. Randomized controlled trials were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool.

Among cohort studies, 21 were rated as high quality (NOS ≥ 7), 10 as moderate quality (NOS 5 - 6), and 3 as low quality (NOS < 5). Most limitations were related to residual confounding and biomarker measurement variability.

Among randomized trials, 9 were judged to have low risk of bias, 3 had some concerns, and 2 had high risk of bias due to deviations from intended interventions or incomplete outcome reporting.

These quality assessments were incorporated into the interpretation of findings, with greater weight given to high-quality longitudinal studies and low-risk randomized trials.

Evidence clustered into three complementary domains:

1) Population epidemiology: hs-cTn predicts HF and mortality; hs-CRP predicts ASCVD risk; several cohorts directly link hs-CRP to hs-cTn or related injury phenotypes [6]-[11].

2) Inflammation biology and cardiometabolic disease: systemic inflammation promotes endothelial dysfunction, oxidative stress, insulin resistance, microvascular dysfunction, and myocardial fibrosis [2]-[5][18]-[21].

3) Therapeutic trials: anti-inflammatory strategies reduce cardiovascular events, supporting causal inference [12]-[16].

A consistent pattern emerges in community cohorts: higher hs-CRP (often in quartiles or clinical cut points) is associated with detectable/elevated hs-cTn after adjustment for demographic factors, BMI, diabetes, hypertension, smoking, lipids, and kidney function [18]-[20]. The JAMA population analysis using a highly sensitive troponin T assay demonstrated that detectable hs-cTnT is associated with structural heart disease and mortality risk, establishing hs-cTn as a subclinical injury biomarker [21]. Subsequent population studies confirmed predictive value for incident events and HF-related outcomes, supporting clinical relevance of low-grade injury signals [22][23].

Although not all cohorts report direct hs-CRP ↔ hs-cTn effect sizes in the same model form, across studies the directionality is consistent: greater systemic inflammatory burden correlates with greater myocardial injury burden [24].

Across major population-based cohorts, systemic inflammation demonstrated a consistent association with subclinical myocardial injury as measured by hs-cTn [25]. In the Atherosclerosis Risk in Communities (ARIC) study and the Multi-Ethnic Study of Atherosclerosis (MESA), individuals in the highest hs-CRP quartile had significantly higher baseline and longitudinal hs-cTn levels compared to those in the lowest quartile [26][27].

Quantitatively, several studies reported that each log-unit increase in hs-CRP was associated with a 10% - 25% higher likelihood of detectable hs-cTn elevation over time [28][29]. In ARIC, elevated hs-CRP was associated with increased odds of incident hs-cTn elevation (adjusted OR ~1.18 per log increase), while MESA demonstrated similar graded associations across inflammatory strata [26][27].

These findings were consistent across additional cohorts including the Cardiovascular Health Study (CHS) and Framingham Offspring Study, reinforcing a reproducible link between systemic inflammation and low-level myocardial injury [30][31].

Troponin-based injury signals appear particularly connected to HF risk—suggesting chronic myocardial stress/remodeling rather than purely plaque-driven ischemic events [6]-[8][30][31]. Mechanistically, inflammation may amplify cardiomyocyte vulnerability through oxidative stress and microvascular dysfunction, driving subtle, repeated injury and remodeling that ultimately manifests as HF, including HFpEF phenotypes [18]-[21][32]-[34].

CANTOS demonstrated that IL-1β inhibition with canakinumab reduced recurrent cardiovascular events independent of lipid lowering, supporting a causal role for inflammation in atherothrombotic risk [12]. In parallel, low-dose colchicine reduced ischemic cardiovascular events after MI (COLCOT) and in chronic coronary disease (LoDoCo2), reinforcing the clinical relevance of inflammatory modulation [13][14]. These trials strengthen the plausibility that upstream inflammatory pathways may also influence myocardial injury trajectories measurable by hs-cTn in earlier prevention stages.

Contemporary prevention frameworks explicitly recognize hs-CRP as a risk-enhancing factor but do not universally incorporate hs-cTn into primary prevention algorithms, despite its prognostic value [35][36]. This gap suggests an opportunity for integrated biomarker approaches, particularly in internal medicine settings managing cardiometabolic risk clusters.

Recent guideline updates and contemporary biomarker research further strengthen the clinical relevance of high-sensitivity cardiac troponin (hs-cTn) in primary prevention. The European Society of Cardiology 2021 cardiovascular disease prevention guidelines formally recognize hs-cTn as a promising biomarker for risk stratification, particularly when used alongside traditional risk scores such as SCORE2 [37]. These guidelines emphasize that hs-cTn captures subclinical myocardial injury not reflected in conventional risk factors, thereby improving identification of individuals at elevated risk despite otherwise intermediate predicted risk profiles [37].

Large-scale prospective cohort analyses published between 2021 and 2025 further support this role. In the Atherosclerosis Risk in Communities (ARIC) Study and Multi-Ethnic Study of Atherosclerosis (MESA), hs-cTn concentrations independently predicted incident heart failure, cardiovascular mortality, and all-cause mortality, even after adjustment for traditional risk factors and inflammatory markers [38][39]. Notably, the addition of hs-cTn to standard risk models resulted in significant improvements in discrimination (C-statistic increases ~0.01 - 0.03) and net reclassification, particularly among individuals categorized as intermediate risk [39][40].

More recent pooled analyses and biomarker-based risk modeling studies have demonstrated that combining hs-cTn with inflammatory markers such as hs-CRP provides complementary prognostic information, reflecting distinct but interrelated pathophysiologic pathways of myocardial injury and systemic inflammation [40]. These multimarker approaches have shown improved prediction of both atherosclerotic cardiovascular disease (ASCVD) events and incident heart failure compared to single-marker strategies, supporting a more integrated framework for early risk detection [38]-[40].

Importantly, however, despite robust prognostic performance, routine clinical implementation of hs-cTn in asymptomatic populations remains limited. Key barriers include the absence of universally accepted decision thresholds, uncertainty regarding optimal screening intervals, and a lack of randomized trial evidence demonstrating that biomarker-guided interventions improve clinical outcomes in primary prevention settings [39][40]. As a result, current guidelines stop short of recommending routine hs-cTn screening, instead positioning it as a risk-enhancing factor that may be selectively incorporated into individualized risk assessment strategies [37]-[40].