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The pathophysiological and clinical relevance of combined measurement of natriuretic peptides and cardiac troponins for risk prediction of incident heart failure in community‐dwelling individuals

Cardiovascular biomarkers, particularly natriuretic peptides (NPs) and cardiac troponins (cTn), are important tools for diagnosis, risk stratification and follow-up of patients with heart failure (HF).1 It is well known that both sex and body mass index (BMI) influence the relationship between the severity of cardiac disease and circulating levels of cardiovascular biomarkers.1–3 Therefore, sex and BMI should be regarded as important confounding factors whenever cardiovascular biomarkers are evaluated, including when they are measured for the prediction of incident HF in the general population.1–3 From a physiological perspective, circulating levels of NPs are higher (about two-fold) in healthy women than in age-matched men during the fertile period of life.1–3 This sex-specific difference is predominantly due to the antagonistic action of sex-steroid hormones on the production of cardiac NPs from cardiomyocytes: oestrogens have a positive action, while male steroid hormones (especially testosterone) a negative one.1–3 On the contrary, circulating levels of cTn are higher in healthy men than in women.1,4–6 Some authors have suggested that circulating levels of cTn, measured with high-sensitivity (hs-cTn) assays, reflect the turnover of cardiomyocytes.4–6 According to this hypothesis, the circulating levels of hs-cTn in healthy adults should be considered as a reliable estimate of the physiological renewal of myocardial tissue, which is on average higher in men than in women.4–6 From a pathophysiological point of view, macrovascular coronary artery disease and myocardial infarction are the leading causes of HF in men,