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R3i EDITORIAL

15 June 2012

Time to prioritise atherogenic dyslipidaemia to reduce residual microvascular risk?

Prof. JC Fruchart, Prof. J. Davignon, Prof. M Hermans

Board of the R3i Trustees
Prof. JC Fruchart, Prof. J. Davignon, Prof. M Hermans Atherogenic dyslipidaemia, the combination of low plasma levels of high-density lipoprotein (HDL) cholesterol and elevated triglycerides, is an important contributor to residual vascular risk. The recent European Atherosclerosis Society Consensus Panel highlighted atherogenic dyslipidaemia as a key driver of cardiovascular risk, especially in individuals with diabetes and/or metabolic disease.(1) Indeed, both low HDL cholesterol and elevated triglycerides are considered risk factors for cardiovascular disease in the latest European guidelines for management of dyslipidaemia.(2)

Evidence also links atherogenic dyslipidaemia with residual microvascular risk in people with diabetes. Observational data have implicated elevated triglycerides or low HDL cholesterol and the development and progression of diabetic retinopathy, nephropathy and neuropathy.(3-6) Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies in type 2 diabetes patients provide further support. Treatment with fenofibrate, which targets atherogenic dyslipidaemia, positively impacted the progression of diabetic retinopathy and albuminuria, as well as reducing lower limb amputations (especially those arising from microangiopathy).(7-12)

This new report from Zoppini et al (2012)(13) provides further support for the importance of targeting atherogenic dyslipidaemia to reduce microvascular complications in people with type 2 diabetes. Their findings were based on a large prospective cohort, followed over about 5 years. The study clearly highlighted the ratio of triglycerides to HDL cholesterol as an important predictor of the risk of microvascular complications, in particular diabetic nephropathy, beyond conventional risk factors such as glycaemic and blood pressure control.

It is also highly relevant that the prognostic significance of an elevated triglyceride-HDL cholesterol ratio was more pronounced in individuals with well controlled plasma levels of low-density lipoprotein (LDL) cholesterol levels. Previous research has already highlighted the high cardiovascular risk in these patients. In the case-control REALIST Macrovascular Study, the presence of both elevated triglycerides (=190 mg/dL or 2.1 mmol/L) and low HDL cholesterol (<30 mg/dL or 0.78 mmol/L), increased coronary risk 10-fold irrespective of LDL-cholesterol control.(14)

As the number of people with type 2 diabetes escalates, particularly in emerging regions such as Asia and the Middle East, with adoption of Westernised lifestyles, and those with diabetes are living longer, due to advances in management and therapy, the burden of diabetes, especially due to microvascular complications has escalated. The cost implications are enormous, given that the presence of diabetes complications more than doubles the cost of care.(15) Taking action now to limit the development of both micro- and macrovascular diabetes complications, not only makes good clinical sense, but also good economic sense.

These new data, added to other studies, provide renewed emphasis on atherogenic dyslipidaemia as an important modifiable contributor to both macrovascular and microvascular risk in patients with type 2 diabetes at LDL cholesterol goal. On this basis, we propose that interventions targeted to atherogenic dyslipidaemia should be a priority, in addition to current standards of care, to reduce the high residual risk of vascular complications that persists in patients with type 2 diabetes.

References

1. Chapman MJ, Ginsberg HN, Amarenco P et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J 2011;32:1345-61.
2. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.
3. Lim LS, Wong TY. Lipids and diabetic retinopathy. Expert Opin Biol Ther 2012;12:93-105.
4. Retnakaran R, Cull CA, Thorne KI et al. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes 2006;55:1832-9.
5. Tesfaye S, Chaturvedi N, Eaton SE et al. Vascular risk factors and diabetic neuropathy. N Engl J Med 2005;352:341-50.
6. Kempler P, Tesfaye S, Chaturvedi N et al. Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med 2002;19:900-9.
7. Keech AC, Mitchell P, Summanen PA et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007;370:1687-97.
8. Ting RD, Keech AC, Drury PL et al. Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study. Diabetes Care 2012;35:218-25.
9. Davis TM, Ting R, Best JD et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia 2011;54:280-90.
10. Rajamani K, Colman PG, Li LP et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 2009;373:1780-8.
11. Chew EY, Ambrosius WT, Davis MD et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010;363:233-44.
12. Mychaleckyj JC, Craven T, Nayak U et al. Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care 2012;35:1008-14.
13. Zoppini G, Negri C, Stoico V, Casati S, Pichiri I, Bonora E. Triglyceride-high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus. Metabolism 2012;61:22-9.
14. Carey VJ, Bishop L, Laranjo N et al. Contribution of high plasma triglycerides and low high-density lipoprotein cholesterol to residual risk of coronary heart disease after establishment of low-density lipoprotein cholesterol control. Am J Cardiol 2010;106:757-63.
15. Pelletier EM, Shim B, Ben-Joseph R, Caro JJ. Economic outcomes associated with microvascular complications of type 2 diabetes mellitus: results from a US claims data analysis. PharmacoEconomics 2009;27:479-90.