Prevalence of systemic inflammation in individuals with atherosclerotic cardiovascular disease: baseline characteristics from the SELECT, SOUL and FLOW phase 3 trials of semaglutide

Abstract Introduction Elevated levels of high-sensitivity C-reactive protein (hsCRP ≥ 2 mg/L) are a marker of systemic inflammation and a risk factor for atherosclerotic cardiovascular disease (ASCVD). We set out to determine the prevalence of systemic inflammation among individuals with ASCVD participating in the SELECT, SOUL and FLOW trials, three ongoing randomized, placebo-controlled, phase 3 trials investigating the efficacy of semaglutide versus placebo. Purpose To evaluate the prevalence of systemic inflammation among people with ASCVD with or without chronic kidney disease (CKD) who are enrolled in SELECT, SOUL and FLOW, and to characterize populations with ASCVD and CKD with and without systemic inflammation. Methods SELECT (NCT03574597) recruited adults ≥ 45 years old with a body mass index (BMI) ≥ 27 kg/m2 and established CVD (previous myocardial infarction, ischaemic or haemorrhagic stroke, or symptomatic peripheral artery disease [PAD]), without diabetes. SOUL (NCT03914326) recruited adults ≥ 50 years old with type 2 diabetes (T2D) and at least one of coronary heart disease, cerebrovascular disease, symptomatic PAD or CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). FLOW (NCT03819153) recruited adults ≥ 18 years old with T2D and CKD (eGFR ≥ 25–≤ 75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio > 100–< 5000 mg/g) treated with renin-angiotensin-aldosterone system-blocking agents. Baseline hsCRP levels were measured in all trials; systemic inflammation was defined as hsCRP ≥ 2 mg/L. Descriptive statistics and chi-squared test with Yates’s correction for continuity were used to analyse the baseline characteristics for individuals with ASCVD (defined as at least one of previous myocardial infarction, stroke or PAD) and CKD stage 3–5 (eGFR < 60 mL/min/1.73 m2). Results A total of 4087 individuals with ASCVD and CKD and 20 331 with ASCVD without CKD were included. Systemic inflammation was present in a significantly larger proportion of individuals with ASCVD and CKD than with ASCVD but without CKD (56.2% vs 46.7%; p < 0.001). In the group with ASCVD, CKD and hsCRP ≥ 2 mg/L, heart failure, PAD and stroke were significantly more prevalent than in the group with hsCRP < 2 mg/L (Table). For individuals with ASCVD and CKD, the following factors were characteristic of systemic inflammation: female sex, smoking, younger age, higher BMI, lower eGFR and high-density lipoprotein cholesterol levels, and higher levels of low-density lipoprotein (LDL) cholesterol, triglycerides and glycated haemoglobin (HbA1c) (Table). Conclusion In these large, ongoing phase 3 trials, systemic inflammation, defined as hsCRP levels ≥ 2 mg/L, was present at baseline in > 55% of individuals with ASCVD and CKD. CV risk factors were more prevalent among individuals with hsCRP ≥ 2 mg/L than in those with hsCRP < 2 mg/L. Interventional studies are warranted to assess to what extent anti-inflammatory agents can address the associated ASCVD risk.Table