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Study of diabetes data reveals influence of multiple manifestations of microvascular disease on development of cardiovascular disease

A recent paper published in the The Lancet Diabetes and Endocrinology is the first to examine the influence of multiple manifestations of microvascular disease on the risk of cardiovascular disease in a large population cohort. Researchers and clinicians from St George’s University Hospitals NHS Foundation Trust and Imperial College London looked at data on 49,027 patients with type 2 diabetes from the UK Clinical Practice Research Datalink. The presence of isolated retinopathy, peripheral neuropathy, or nephropathy, independent of conventional risk factors, were found to confer at least a similar risk of cardiovascular events as uncontrolled established risk factors including blood pressure (?140/90 mmHg), HbA1c (?7.0%) and low-density cholesterol (? 2.5 mmol/L). Individuals with disease in multiple microvascular beds were, in a “dose dependent fashion”, at the greatest overall risk of cardiovascular disease. For individuals with one, two or three microvascular disease states versus none, the multivariable-adjusted hazard ratios for the primary outcome were 1·32 (1·16-1·50), 1·62 (1·42-1·85) and 1.99 (1·70-2.34), respectively. Similar trends were observed for cardiovascular death, all-cause mortality and for hospitalisation for heart failure. It might be possible to mitigate against this excess risk, as researchers observed that among those with multiple microvascular disease states, event rates were substantially lower when HbA1c, BP and LDL-C were better controlled.

The inclusion of microvascular disease variables in cardiovascular risk algorithms resulted in a net correct reclassification of 3.6% of the cohort into higher- or lower-risk strata that are currently used in the UK and US to determine the need for preventive treatments such as statins. If information on microvascular disease were incorporated presently then 9·3% of individuals previously considered as eligible for moderate intensity statins in US guidance (predicted risk <7.5%) would be considered as candidates for high intensity statin therapy (observed risk 8·6%). Similarly, microvascular disease would reclassify 9·0% of individuals in a higher risk group (predicted risk ?7.5%), currently considered eligible for high intensity statins, to a group who could be offered moderate intensity therapy (observed risk 6·3%).

In reference to UK NICE guidance, of those currently considered ineligible for statin therapy (predicted risk <10%), 8·9% would be reclassified into a higher risk group with an observed event rate of 11·6%. Of individuals currently offered statin therapy (predicted risk ?10%), 12·3% would be reclassified into a lower risk group with an observed 10-year event rate of 8·1%. Based on the current prevalence of type 2 diabetes, in absolute terms this would represent a change in statin prescriptions for 10·6% of individuals with type 2 diabetes in the UK and 9·1% of those in the US, with accurate reclassification in 59·5% and 65·7%, respectively. This figure corresponds to 370 000 of the 3.2 million people living with type 2 diabetes in the UK presently, and 2.5 million of the 28 million people affected by the condition in the US.

The authors concluded that as the assessment of microvascular disease should be part of routine clinical practice among those with diabetes, the findings could offer a simple, convenient and cheap method for improving risk prediction as compared to more expensive blood based biomarkers or non-invasive imaging modalities for better targeting preventive therapies. High microvascular disease burden could be used as criteria to enrich future clinical outcome trials, identifying a very high risk cohort of patients who might derive greater absolute benefit from more intensive risk factor control with conventional or novel therapies. It is hoped that the observations should encourage further research including a better understanding of the impact of microvascular disease with different cardiovascular outcomes.

Article: Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study, Brownrigg JRW, MRCS, Hughes CO, MRCS, Burleigh D, MSc, Karthikesalingam A, PhD, Patterson BO, PhD, Holt PJ, PhD, Thompson MM, MD, de Lusignan S, MD, Ray KK, MD, MPhil, Hinchliffe RJ, MD, The Lancet Diabetes and Endocrinology, doi: 10.1016/S2213-8587(16)30057-2, published online 20 May 2016.