Cardiovascular risk in inflamed Danish women and men without standard modifiable risk factors

Aims Elevated hsCRP levels correlate with high risk of cardiovascular disease in American women without standard modifiable cardiovascular risk factors (“SMuRF-less”). We examined whether elevated hsCRP levels are associated with cardiovascular risk in low-risk Danish women and men without standard modifiable risk factors using a prospective cohort design. Methods We included all SMuRF-less and SCORE2/SCORE2-OP/PREVENT low-risk individuals aged 20-100 years without cardiovascular disease from the Copenhagen General Population Study. Using cause-specific Cox models, we constructed age and sex adjusted cumulative incidence curves and calculated multivariable adjusted hazard ratios for major adverse cardiovascular events (MACE), coronary heart disease, and ischaemic stroke across baseline hsCRP clinical thresholds (<1, 1 to <3, and ≥3 mg/L) and tertiles (<0.9, 0.9 to <1.5, and ≥1.5 mg/L). Results We identified 21,085 SMuRF-less, 49,425 SCORE2/SCORE2-OP low-risk, and 58,739 PREVENT low-risk individuals in whom 895, 2,004, and 2,598 MACE events accrued during median 11.4 years of follow-up. The cumulative incidences of MACE and coronary heart disease increased across hsCRP clinical thresholds and tertiles in all populations. The cumulative incidence of ischaemic stroke was only slightly higher in those with elevated hsCRP levels. In the SMuRF-less individuals, the multivariable adjusted HRs (95% CI) for MACE were 1.35 (1.08- 1.68) and 1.36 (1.14-1.62) for the highest vs. lowest clinical threshold and tertile, respectively. The corresponding estimates were 1.47 (1.27-1.71) and 1.39 (1.24-1.57) for the SCORE2/SCORE2-OP and 1.36 (1.20-1.55) and 1.33 (1.20-1.47) for the PREVENT low-risk individuals, respectively. Conclusion Elevated hsCRP levels are associated with increased risk of future cardiovascular disease in low-risk Danish women and men.