Risk factor control and cardiovascular event risk in people with type 2 diabetes in primary and secondary prevention settings

Background: To examine the association between the degree of risk factor control and cardiovascular disease (CVD) risk in type 2 diabetes and to assess if the presence of cardio-renal disease modifies these relationships. Methods: A retrospective cohort study using data from English practices from The Clinical Practice Research Datalink (CPRD GOLD) and the Scottish Care Information-Diabetes dataset (SCI-Diabetes), with linkage to hospital and mortality data. We identified 101,749 with type 2 diabetes (T2D) in CPRD matched with 378,938 controls without diabetes and 330,892 with type 2 diabetes in SCI-Diabetes between 2006 and 2015. The main exposure was number of ‘optimised’ risk factors: non-smoker, total cholesterol≤4mmol/L, triglycerides≤1.7mmol/L, HbA1c≤53mmol/mol (≤7.0%), systolic blood pressure<140mmHg or <130mmHg if ‘high risk’. Cox models were used to assess cardiovascular risk associated with levels of risk factor control. Results: In CPRD, the mean baseline age in T2D was 63 years and 28% had cardio-renal disease (SCI-Diabetes: 62 years; 35% cardio-renal disease). Over 3 years follow-up (SCI-Diabetes: 6 years), CVD events occurred among 27,900 (27%) CPRD-T2D, 101,362 (31%) SCI-Diabetes-T2D and 75,520 (19%) CPRD-controls. In CPRD, compared to controls, T2D participants with optimal risk factor control (ORFC; all risk factors controlled) had a higher risk of CVD events (adjusted hazard ratio 1.21; 95% confidence interval 1.12-1.29). In T2D participants from CPRD and SCI-Diabetes, pooled HRs for CVD associated with five risk factors being elevated vs. ORFC were 1.09 (1.01-1.17) in people with cardio-renal disease but 1.96 (1.82-2.12) in people without cardio-renal disease. People without cardio-renal disease were younger and more likely to have likely to have sub-optimal risk factor control but had fewer prescriptions for risk factor modifying medications than those with cardio-renal disease. Conclusions: Optimally managed people with T2D have a 21% higher CVD risk when compared to controls. People with T2D without cardio-renal disease would be predicted to benefit greatly from CVD risk factor intervention.