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Eur J Clin Invest. 2009 Aug;39(8):680-8. doi: 10.1111/j.1365-2362.2009.02155.x. Epub 2009 May 12.

Low plasma HDL-c, a vascular risk factor in high risk patients independent of LDL-c.

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Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.



High concentrations of high density lipoprotein-cholesterol (HDL-c) are associated with lower cardiovascular risk, but it is not known whether this is also the case in the presence of intensive low density lipoprotein-cholesterol (LDL-C) therapy. In this study, we determined the relationship between HDL-c and new non-fatal or fatal vascular events in patients with various manifestations of clinical evident vascular disease and evaluated whether this relationship is modified by LDL-c levels.


Prospective single centre, cohort study of 3837 patients with a history or recent diagnosis of clinical manifest vascular disease (coronary, cerebrovascular, peripheral arterial disease or abdominal aortic aneurysm) The relationship between HDL-c quintiles and time to a new event (myocardial infarction, ischaemic stroke, vascular death) was quantified with Cox-regression models and adjusted for potential confounders (age, gender, body mass index, type 2 diabetes, triglycerides, smoking, use of alcohol and lipid-lowering therapy). Effect modification of LDL-c was assessed with interaction terms.


During a median follow up of 3.3 (range 0.1-9.5) years, a total of 465 first new events occurred. Compared with the lowest quintile, the upper quintile of HDL-c levels was associated with a lower risk for new events; Hazard Ratio 0.61 (95% CI 0.43-0.86) irrespective of the localisation of vascular disease and use of lipid-lowering medication. Higher HDL-c levels were associated with comparably lower risks for vascular events in patients with LDL-c levels above and below 2.5 mmol L(-1) (P-values for interaction > 0.05).


Patients with various clinical manifestations of vascular diseases in the highest HDL-c quintile have a lower risk for vascular events compared with patients in the lowest HDL-c quintile. Further, the current results expand the evidence by showing that also in a cohort of patients with various localisations of clinical evident vascular disease, in which statins were widely used, higher HDL-c levels confer a lower risk for developing new vascular events, irrespective of the localisation of vascular disease, use of lipid-lowering medication and plasma LDL-c concentration.

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