Author + information
- Received March 21, 2013
- Accepted April 9, 2013
- Published online November 12, 2013.
- Anton P. van de Woestijne, MD∗,
- Yolanda van der Graaf, MD, PhD†,
- An-Ho Liem, MD, PhD‡,
- Maarten J.M. Cramer, MD, PhD§,
- Jan Westerink, MD, PhD∗,
- Frank L.J. Visseren, MD, PhD∗∗ (, )
- SMART Study Group
- ∗Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- †Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
- ‡Department of Cardiology, Sint Franciscus Gasthuis, Rotterdam, the Netherlands
- §Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
- ↵∗Reprint requests and correspondence:
Dr. Frank L. J. Visseren, Department of Vascular Medicine, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, the Netherlands.
Objectives This study sought to evaluate the vascular risk of low high-density lipoprotein-cholesterol (HDL-C) in relation to the use and intensity of lipid-lowering medication in patients with clinically manifest vascular diseases.
Background Low levels of HDL-C are associated with an increased risk for vascular diseases and may contribute to residual vascular risk in patients already treated for other risk factors. However, post-hoc analyses from statin trials indicate that the vascular risk associated with low HDL-C may be low or even absent in patients using intensive statin therapy.
Methods We performed a prospective cohort study of 6,111 patients with manifest vascular disease. Cox proportional hazards models were used to evaluate the risk of HDL-C on vascular events in patients using no, usual dose, or intensive lipid-lowering therapy.
Results New vascular events (myocardial infarction, stroke, or vascular death) occurred in 874 subjects during a median follow-up of 5.4 years (interquartile range: 2.9 to 8.6 years). In patients not using lipid-lowering medication at baseline (n = 2,153), a 0.1 mmol/l increase in HDL-C was associated with a 5% reduced risk for all vascular events (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.92 to 0.99). In patients on usual dose lipid-lowering medication (n = 1,910) there was a 6% reduced risk (HR: 0.94; 95% CI: 0.90 to 0.98). However, in patients using intensive lipid-lowering treatment (n = 2,046), HDL-C was not associated with recurrent vascular events (HR: 1.02; 95% CI: 0.98 to 1.07) irrespective of low-density lipoprotein cholesterol level.
Conclusions In patients with clinically manifest vascular disease using no or usual dose lipid-lowering medication, low plasma HDL-C levels are related to increased vascular risk, whereas in patients using intensive lipid-lowering medication, HDL-C levels are not related to vascular risk.
The SMART study was financially supported by a grant of the University Medical Centre Utrecht. Dr. Visseren’s department receives grant support from the Netherlands Organisation for Health Research and Development and the Catharijne Foundation Utrecht; and speaker fees from Merck. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 21, 2013.
- Accepted April 9, 2013.
- American College of Cardiology Foundation