Circulating C-Type Natriuretic Peptide and Its Relationship to Cardiovascular Disease in the General Population

Abstract

C-type natriuretic peptide (CNP) is an endothelium-derived peptide that is released as a protective mechanism in response cardiovascular injury and/or disease. However no studies have investigated circulating CNP, identifying clinical factors that may influence CNP and its relationship to cardiovascular disease in the general population. We studied 1,841 randomly selected subjects from Olmsted County, Minnesota, USA (mean age 63 ± 11 years; 48% male). Plasma CNP was measured by a well-established radioimmunoassay and echocardiography, clinical characterization and detailed medical record review were performed. We report that CNP circulates at various concentrations (median 13 pg/ml), was unaffected by gender, was weakly associated by age and that highest quartile of CNP identified a high-risk phenotype. Subjects with CNP in the highest quartile were associated with increased risk of myocardial infarction (multi-variable adjusted hazard ratio, 1.51; 95% confidence interval, 1.09–2.09; P= 0.01) but not heart failure, cerebrovascular accidents or death over a follow-up of 12 years. Addition of the highest quartile of CNP to clinical variables led to a modest increase in the integrated discrimination improvement for risk of myocardial infarction. In a large community-based cohort elevated circulating CNP identified a high-risk phenotype that included cardiovascular comorbidities and left ventricular dysfunction, and provided evidence that highest concentrations of CNP potentially has prognostic value in predicting future risk of myocardial infarction. Together, these data from the general population highlights the potential value of CNP and supports the need for additional studies to evaluate whether mechanisms regulating CNP could improve outcomes.

Neurohumoral Modulation During Waon Therapy in Chronic Heart Failure ― Subanalysis of Waon-CHF Study ―

“…19,20 Plasma CNP22 level (pg/mL) was determined using a nonequilibrium radioimmunoassay (Phoenix Pharmaceutical, Burlingame, CA, USA), using an antibody that detects human CNP22 as previously described. 21 Inter-and intraassay variability was 11% and 5% respectively. Recovery was 85%.…”

“…Finally, endothelial impairment according to CNP levels was more improved in patients with renal impairment. CNP production is stimulated by endothelial damage by pro-inflammatory cytokines or shear stress, 17 so a high circulating levels can predict the risk of myocardial infarction, 21 and CNP plays a role in coronary relaxation via NO system, 27 suggesting a potential link to NO and endothelial injury in which Waon therapy is also involved. Therefore, we speculate patients with renal impairment would be a potential target for Waon therapy.…”

The role of natriuretic peptides in regulation of cardiovascular system

“…Они показали, что отсутствие CNP в организме приводит к эндотелиальной дисфункции, гипертензии, атерогенезу и образованию артериальных аневризм [208], а также к развитию фиброза и ремоделирования предсердий и дисфункции синусового узла со склонностью к развитию фибрилляции предсердий [78]. Кроме того, популяционное проспективное исследование показало, что верхний квартиль концентрации CNP в циркулирующей крови ассоциирован с повышенным риском возникновения инфаркта миокарда [270]. Таким образом, CNP является важным кратко-и долгосрочным регулятором структурно-функциональной интегральности сосудов.…”

Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy

“…CNP, which is primarily released by the endothelial cells, acts primarily on NPR B, which is expressed in vascular smooth muscle cells. CNP has less of an impact on sodium and water retention [3,6].…”