Low-density lipoprotein (LDL) particles are causally involved in the pathogenesis of atherosclerosis and an extensive body of evidence shows that lowering of LDL cholesterol levels reduce risk of coronary artery disease. Similarly, elevated glucose levels have been shown to have a causal effect on risk of coronary artery disease in individuals with and without diabetes. The evidence of a causal involvement of LDL and glucose in risk of peripheral vascular disease is less explored.
We aimed to assess whether levels of 1) LDL cholesterol and 2) glucose are causally associated with high risk of peripheral micro- and macrovascular disease in individuals in the general population using Mendelian randomization. Our findings indicate that LDL cholesterol has a causal effect on risk of peripheral macrovascular but not microvascular disease. Glucose has a causal effect on risk of microvascular disease also at levels below the diabetic threshold. Further studies are needed to confirm a potential causal effect of glucose levels on peripheral arterial disease.
These findings are important as they add to a sparse existing body of evidence of genetic studies supporting a causal effect of LDL cholesterol and glucose on risk of micro- and macrovascular disease in the general population.
Place of employment
Date and place of defense
28th November 2019
Marianne Benn, Chief Physician, Professor, Department of Clinical Biochemistry, Rigshospitalet (main)
Børge Nordestgaard, Chief Physician, Professor, Department of Clinical Biochemistry, Herlev and Gentofte Hospital