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

Abstract

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.

Keywords: Biomarker; CRP; Cardiovascular disease; Inflammation; Prediction; Prognosis; SCREAM.

Structured Graphical Abstract

Systemic inflammation and health outcomes in adults receiving treatment for atherosclerotic cardiovascular disease. AR, absolute risk; aRR, adjusted rate ratio; ASCVD, atherosclerotic cardiovascular disease; CI, confidence interval; CRP, C-reactive protein; HCRU, healthcare resource utilization; HR, hazard ratio; MACE, major adverse cardiovascular events; SCREAM, Stockholm CREAtinine Measurements.

Figure 1

Patient selection flow chart. ASCVD, atherosclerotic cardiovascular disease

Figure 2

Cumulative incidence curves depicting the cumulative incidence of (A) major adverse cardiovascular events, (B) heart failure hospitalization, and (C) all-cause mortality associated with baseline C-reactive protein categories. MACE, major adverse cardiovascular events

Figure 3

Subgroup analyses: forest plots of C-reactive protein ≥ 2 mg/L (vs. C-reactive protein < 2 mg/L) and rate of major adverse cardiovascular events. ^Models were adjusted (when appropriate) for age, sex, time since atherosclerotic cardiovascular disease, estimated glomerular filtration rate, albuminuria, comorbidities (diabetes mellitus, hypertension, chronic respiratory disease, cancer, myocardial infarction, angina, heart failure, peripheral vascular disease, stroke/transient ischaemic attack, atrial fibrillation, and rheumatoid diseases), undertaken procedures (coronary artery bypass grafting and percutaneous coronary intervention), and ongoing medications (antiplatelet, non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, beta-blockers, sodium-glucose co-transporter 2 inhibitors, diuretics, calcium channel blockers, digoxin, lipid-lowering treatment (statins, pro-protein convertase subtilisin/kexin type 9 inhibitors, and ezetimibe). CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; MACE, major adverse cardiovascular events