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(Circulation. 2005;112:3058-3065.)
© 2005 American Heart Association, Inc.

Coronary Heart Disease

Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

Chris J. Packard, DSc; Ian Ford, PhD; Michele Robertson, BSc; James Shepherd, MD; Gerard J. Blauw, MD; Michael B. Murphy, MD; Edward L.E.M. Bollen, MD; Brendan M. Buckley, FRCPI; Stuart M. Cobbe, MD; Allan Gaw, MD; Michael Hyland, FRCPI; J. Wouter Jukema, MD; Adriaan M. Kamper, MD; Peter W. Macfarlane, DSc; Ivan J. Perry, MD; David J. Stott, MD; Brian J. Sweeney, FRCPI; Cillian Twomey, FRCPI; Rudi G.J. Westendorp, MD, for the PROSPER Study Group

From the Department of Vascular Biochemistry (C.J.P., J.S.), Division of Cardiovascular and Medical Sciences (S.M.C., P.W.M.), and Department of Geriatric Medicine (D.J.S.), University of Glasgow, Glasgow, Scotland; Clinical Trials Unit (A.G.), North Glasgow Division, Greater Glasgow Health Board, Glasgow, Scotland; Robertson Centre for Biostatistics (I.F., M.R.), University of Glasgow, Glasgow, Scotland; Department of Pharmacology and Therapeutics (B.M.B., M.B.M.), Cork University Hospital, Wilton, Cork, Ireland; Department of Epidemiology and Public Health (I.J.P.), Departments of Geriatric Medicine (M.H., C.T.), and Department of Neurology (B.S.), Cork University Hospital, Wilton, Cork, Ireland; Section of Gerontology and Geriatrics (G.J.B., R.G.J., A.M.K.) and Departments of Cardiology (J.W.J.) and Neurology (E.L.E.M.), Leiden University Medical Centre, Leiden, The Netherlands.

Correspondence to Prof C.J. Packard, Glasgow Royal Infirmary, Department of Vascular Biochemistry, 4th Floor, University Block, Glasgow G31 2ER, UK. E-mail chris.packard{at}clinmed.gla.ac.uk

Received December 2, 2004; revision received August 17, 2005; accepted August 18, 2005.

Background— Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

Method and Results— The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (P=0.27), nor did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely associated with risk in subjects on placebo (P=0.0019) but not in those on pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy.

Conclusions— In people >70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio >3.3.

Key Words: coronary disease • risk factors • cholesterol • drugs

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