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; Ian Ford; Michele Robertson; James Shepherd; Gerard J. Blauw; Michael B. Murphy; Edward L.E.M. Bollen; Brendan M. Buckley; Stuart M. Cobbe; Allan Gaw; Michael Hyland; JW Jukema; Adriaan M. Kamper; Peter W. Macfarlane; Ivan J. Perry; David J. Stott; Brian J. Sweeney; Cillian Twomey; Rudi G.J. Westendorp

doi:10.1161/circulationaha.104.526848

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^*, Ian Ford, Michele Robertson, James Shepherd, Gerard J. Blauw, Michael B. Murphy, Edward L.E.M. Bollen, Brendan M. Buckley, Stuart M. Cobbe, Allan Gaw, Michael Hyland, JW Jukema, Adriaan M. Kamper, Peter W. Macfarlane, Ivan J. Perry, David J. Stott, Brian J. Sweeney, Cillian Twomey, Rudi G.J. Westendorp

^*Corresponding author for this work

School of Psychology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	3058-3065
Number of pages	0
Journal	Circulation
Volume	112
Issue number	20
DOIs	https://doi.org/10.1161/circulationaha.104.526848
Publication status	Published - 15 Nov 2005

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10.1161/circulationaha.104.526848

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Packard, C. J., Ford, I., Robertson, M., Shepherd, J., Blauw, G. J., Murphy, M. B., Bollen, E. L. E. M., Buckley, B. M., Cobbe, S. M., Gaw, A., Hyland, M., Jukema, JW., Kamper, A. M., Macfarlane, P. W., Perry, I. J., Stott, D. J., Sweeney, B. J., Twomey, C., & Westendorp, R. G. J. (2005). Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation, 112(20), 3058-3065. https://doi.org/10.1161/circulationaha.104.526848

@article{b0514ebcb7054cd785987aadc3473262,

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

abstract = " 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. ",

author = "Packard, {Chris J.} and Ian Ford and Michele Robertson and James Shepherd and Blauw, {Gerard J.} and Murphy, {Michael B.} and Bollen, {Edward L.E.M.} and Buckley, {Brendan M.} and Cobbe, {Stuart M.} and Allan Gaw and Michael Hyland and JW Jukema and Kamper, {Adriaan M.} and Macfarlane, {Peter W.} and Perry, {Ivan J.} and Stott, {David J.} and Sweeney, {Brian J.} and Cillian Twomey and Westendorp, {Rudi G.J.}",

year = "2005",

month = nov,

day = "15",

doi = "10.1161/circulationaha.104.526848",

language = "English",

volume = "112",

pages = "3058--3065",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "20",

}

Packard, CJ, Ford, I, Robertson, M, Shepherd, J, Blauw, GJ, Murphy, MB, Bollen, ELEM, Buckley, BM, Cobbe, SM, Gaw, A, Hyland, M, Jukema, JW, Kamper, AM, Macfarlane, PW, Perry, IJ, Stott, DJ, Sweeney, BJ, Twomey, C & Westendorp, RGJ 2005, 'Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)', Circulation, vol. 112, no. 20, pp. 3058-3065. https://doi.org/10.1161/circulationaha.104.526848

TY - JOUR

T1 - Plasma Lipoproteins and Apolipoproteins as Predictors of Cardiovascular Risk and Treatment Benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

AU - Packard, Chris J.

AU - Ford, Ian

AU - Robertson, Michele

AU - Shepherd, James

AU - Blauw, Gerard J.

AU - Murphy, Michael B.

AU - Bollen, Edward L.E.M.

AU - Buckley, Brendan M.

AU - Cobbe, Stuart M.

AU - Gaw, Allan

AU - Hyland, Michael

AU - Jukema, JW

AU - Kamper, Adriaan M.

AU - Macfarlane, Peter W.

AU - Perry, Ivan J.

AU - Stott, David J.

AU - Sweeney, Brian J.

AU - Twomey, Cillian

AU - Westendorp, Rudi G.J.

PY - 2005/11/15

Y1 - 2005/11/15

N2 - 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.

AB - 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.

U2 - 10.1161/circulationaha.104.526848

DO - 10.1161/circulationaha.104.526848

M3 - Article

SN - 0009-7322

VL - 112

SP - 3058

EP - 3065

JO - Circulation

JF - Circulation

IS - 20

ER -

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

Abstract

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