Baseline high sensitivity C-Reactive Protein predicts incident cardiovascular events and all-cause mortality in the ASCOT Study at 20-years

Abstract

Abstract Introduction The prediction of future cardiovascular events in those at greatest risk is essential to optimise preventative therapies appropriately and effectively. The value of high sensitivity C-reactive Protein (hsCRP) has been questioned in this regard, and recent studies have suggested the utility of this widely assessed biomarker for predicting future mortality in those presenting with suspected myocardial infarction (MI), however the relationship in stable patients is still debated. Purpose To investigate the role of baseline hsCRP for predicting long-term incident cardiovascular events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), with follow-up extending to 20-years. Methods This ASCOT legacy study reports events after 20-years of the UK participants in the original ASCOT trial. ASCOT was a multicentre randomised trial, randomising patients with hypertension into amlodipine-based or atenolol-based blood pressure-lowering (BPL) treatment. In addition, those with total cholesterol <6.5 mmol/L and no previous lipid-lowering treatment underwent further randomisation to either atorvastatin or placebo as part of the lipid-lowering (LL) arm of ASCOT. We examined outcomes related to hsCRP levels in the LL arm, dichotomously (< or > 2mg/L), in tertiles or continuously, adjusting in Model 1 (age, sex, socio-economic status [years of education] and ethnicity) and Model 2 (Model 1 plus current smoker, body mass index, baseline systolic blood pressure, creatinine, diabetes, history of vascular diseases, history of antihypertensive medication and allocation to BPL and LL). All-cause mortality, non-fatal and fatal MI, total coronary events and procedures and total cardiovascular events were assessed. Results 5,294 participants were included in the final cohort, after exclusion of 3,286 participants in the LL arm (n=8,580) without hsCRP data. There were no substantial differences in baseline characteristics between treatment allocation arms (non-randomised, placebo or atorvastatin). The highest tertile of hsCRP (median [IQR], 6.41 [4.81-10.44]) strongly related to all-cause mortality, withstanding adjustment in both Model 1 (HR 95% CI, 1.38 [1.27-1.53]; p<0.001; p<0.001 for interaction) and Model 2 (HR 1.25 [1.10-1.42]; p<0.001; p<0.001 for interaction). Moreover, the highest hsCRP tertile also related to fatal and non-fatal MI (Model 2 – HR 1.32 [1.05-1.67]; p=0.020; p=0.019 for interaction); total coronary events and procedures (Model 2 – HR 1.27 [1.09-1.47]; p=0.002; p=0.003 for interaction); and total cardiovascular events (Model 2 – HR 1.22 [1.08-1.37]; p=0.001; p=0.001 for interaction). Conclusions This study demonstrates that one hsCRP reading at baseline independently predicts cardiovascular events and all-cause mortality at very long-term follow-up in patients at high-risk for these events, and may help stratify patients into higher risk categories for intensive preventative strategies.