Calprotectin Shows Promise as Independent Biomarker for ASCVD: JAMA

Calprotectin, a marker of neutrophil activation, has been recognized to be an important player in inflammation, which is at the core of atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Its understanding as a potential predictor of ASCVD may lead to enhanced early identification of individuals at high risk.

The research comprised 2,412 Dallas Heart Study participants, who were a multiethnic population-based cohort. Plasma samples taken at phase 2 of the study were used to measure calprotectin levels. Participants were followed up for a median of 8 years to assess the incidence of ASCVD events such as nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, and cardiovascular mortality.

The association between calprotectin levels and ASCVD events was examined by Cox proportional hazards models, which controlled for recognized cardiovascular risk factors, such as high-sensitivity C-reactive protein (hs-CRP), N-terminal pro–brain natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT). The research also determined the effect of calprotectin on coronary artery calcium scores, an indicator of atherosclerosis. Additionally, experiments in vitro assessed the role of calprotectin in the mechanisms of endothelial dysfunction in order to elucidate the possible ways of progression in ASCVD.

Key Findings

Association with ASCVD Events:

• A multivariable adjusted model demonstrated an association of a higher risk for ASCVD events over 8 years in conjunction with increased calprotectin levels.

• A significant association of calprotectin increase was noted between each log value and 98% increased ASCVD events HR: 1.98; 95% CI, 1.54-2.53.

• Even after adjustment for the traditional risk factors, the association remained significant, with an HR of 1.61 (95% CI, 1.22-2.13), and even after further adjustment for hs-CRP, NT-proBNP, and hs-cTnT, it remained significant with an HR of 1.43 (95% CI, 1.04-1.96).

Demographic Associations:

• Higher calprotectin levels were more common among older individuals, males, individuals of Black race, and those with hypertension, diabetes, and smoking history.

• Volunteers with increased calprotectin also had increased hemoglobin A1c, extremely low-density lipoprotein cholesterol, and triglycerides but decreased high-density lipoprotein cholesterol and cholesterol efflux capacity.

Effect on Coronary Artery Calcium:

• Increased calprotectin levels correlated with substantially greater coronary artery calcium scores (P <.001), suggesting an association between calprotectin and severity of atherosclerosis.

Mechanistic Insights:

• In vitro experiments showed that calprotectin damages coronary endothelial integrity, decreases nitric oxide production, and enhances endothelial-to-mesenchymal transition. These actions indicate a direct role of calprotectin in ASCVD development.

The study authors concluded that elevated calprotectin levels were independently linked to a higher risk of ASCVD in a multiethnic population, affirming its utility as a potential biomarker for cardiovascular risk.

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