Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease.

Background and aims

The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts.

Methods

This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein ≥ 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death.

Results

A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein ≥ 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein ≥ 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein ≥ 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events.

Conclusions

Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

CommentIn

doi: 10.1093/eurheartj/ehae565

References:

• Tsao  CW, Aday  AW, Almarzooq  ZI, Alonso  A, Beaton  AZ, Bittencourt  MS, et al.  Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation  2022;145:e153–639. 10.1161/cir.0000000000001052
• Kaasenbrood  L, Boekholdt  SM, van der Graaf  Y, Ray  KK, Peters  RJ, Kastelein  JJ, et al.  Distribution of estimated 10-year risk of recurrent vascular events and residual risk in a secondary prevention population. Circulation  2016;134:1419–29. 10.1161/circulationaha.116.021314
• Pradhan  AD, Aday  AW, Rose  LM, Ridker  PM. Residual inflammatory risk on treatment with PCSK9 inhibition and statin therapy. Circulation  2018;138:141–9. 10.1161/CIRCULATIONAHA.118.034645
• Zacho  J, Tybjaerg-Hansen  A, Jensen  JS, Grande  P, Sillesen  H, Nordestgaard  BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med  2008;359:1897–908. 10.1056/NEJMoa0707402
• Guijarro  C. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation  2001;104:e127. 10.1161/circ.104.22.e127