Soluble Corin Predicts the Risk of Cardiovascular Disease

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  Central Illustration. An Illustration of the Hypothesis of Our Study Corin can activate atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), both of which are the main constitutes of the natriuretic peptides system that maintains blood pressure homeostasis through natriuresis, diuresis, and vasodilatation. It may play a switching role in the natriuretic peptides system, thereby delivering an impact on the cardiovascular system. Corin protein was found to be shed from the cardiac myocyte surface. Shed corin molecules could apparently enter the circulation and were found to possess the same activity in activating ANP as the membrane-bound corin. Therefore, we speculated that serum corin may be associated with cardiovascular disease (CVD). mRNA = messenger RNA; NPRA = natriuretic peptide receptor A; NPRB = natriuretic peptide receptor B.

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  Figure 1. Serum Corin Levels for Participants With Different Outcomes During Follow-Up Compared with participants who remained free of any events (median: 1,665.2 pg/mL; IQR: 1,378.6-2,079.4 pg/mL), those who died of noncardiovascular causes (median: 1,750.1 pg/mL; IQR: 1,377.5-2,178.5 pg/mL; P = 0.590) or were lost to follow-up (median: 1,736.1 pg/mL; IQR: 1,441.6-2,111.7 pg/mL; P = 0.091) had a similar level of serum corin, whereas those who developed cardiovascular disease (CVD) (median: 1,850.5 pg/mL; IQR: 1,533.7-2,303.9 pg/mL; P < 0.001), stroke (median: 1,909.9 pg/mL; IQR: 1,557.9-2,400.5 pg/mL; P < 0.001), and coronary heart disease (CHD) (median: 1,846.3 pg/mL; IQR: 1,511.7-2,288.4 pg/mL; P = 0.003) had a significantly increased level of serum corin at baseline.

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  Figure 2. Cumulative Incidence of CVD According to Quartiles of Serum Corin The cumulative incidence of cardiovascular disease (CVD) was 6.08%, 7.87%, 9.25%, and 10.43% in participants with increasing quartiles of serum corin at baseline, respectively, with a significant group difference (P = 0.038 for the Fine-Gray test).

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  Figure 3. Cubic Spline Curves Visualizing the Impact of Corin on CVD HRs (red line) and their 95% CIs (gray shading) of cardiovascular disease (CVD) associated with baseline serum corin levels were calculated by constructing a restricted cubic spline regression model, after adjusting for age, sex, education level, current smoking, current drinking, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, and antihypertension medications at baseline.

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  Figure 4. Cumulative Incidence of Stroke According to Quartiles of Serum Corin The cumulative incidence of stroke was 1.92%, 2.89%, 3.51%, and 5.78% in participants with increasing quartiles of serum corin at baseline, respectively, with a significant group difference (P = 0.002 for the Fine-Gray test).

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  Figure 5. Cubic Spline Curves Visualizing the Impact of Corin on Stroke HRs (red line) and their 95% CIs (gray shading) of stroke associated with baseline serum corin levels were calculated by constructing a restricted cubic spline regression model, after adjusting for age, sex, education level, current smoking, current drinking, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, and antihypertension medications at baseline.