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

Author:

Mazhar Faizan1,Faucon Anne-Laure1ORCID,Fu Edouard L12,Szummer Karolina E3,Mathisen Jimmi4,Gerward Sofia4,Reuter Simon Bertram4,Marx Nikolaus5ORCID,Mehran Roxana6ORCID,Carrero Juan-Jesus17ORCID

Affiliation:

1. Department of Medical Epidemiology and Biostatistics, Campus Solna, Karolinska Institutet , Nobels väg 12A, 171 65 Stockholm , Sweden

2. Department of Clinical Epidemiology, Leiden University Medical Center , Leiden , The Netherlands

3. Department of Cardiology, Karolinska Institutet, Karolinska University Hospital , Huddinge, Stockholm , Sweden

4. Novo Nordisk A/S , Søborg , Denmark

5. Department of Internal Medicine I, RWTH Aachen University , Aachen , Germany

6. Mount Sinai School of Medicine, Mount Sinai Health System , New York City, NY , USA

7. Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital , Danderyd , Sweden

Abstract

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.

Funder

Novo Nordisk

Swedish Research Council

US National Institute of Health

Swedish Heart and Lung Foundation

Region Stockholm

Publisher

Oxford University Press (OUP)

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