(Circulation. 1995;92:1758-1764.)
© 1995 American Heart Association, Inc.
Articles |
Kuopio Atherosclerosis Prevention Study (KAPS)
A Population-Based Primary Preventive Trial of the Effect of LDL Lowering on Atherosclerotic Progression in Carotid and Femoral Arteries
From the Research Institute of Public Health, University of Kuopio (Finland) (R.S., K.N., E.P. J.R., J.T.S.), and the Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ (R.B., J.-S.P.).
Correspondence to Prof Jukka T. Salonen, Research Institute of Public Health, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.
Background The atherosclerotic progression–reducing effect of LDL cholesterol (LDL-C) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis. KAPS (Kuopio Atherosclerosis Prevention Study) is the first population-based trial in the primary prevention of carotid and femoral atherosclerosis.
Methods and Results The eligibility requirements were serum LDL-C
4.0 mmol/L and total cholesterol <7.5 mmol/L. Out of a
geographically defined population, 447 men aged 44 to 65 years (mean,
57) were randomized to pravastatin (40 mg/d) or placebo for
3 years. Less than 10% of the subjects had prior myocardial
infarction. Thirty-nine men discontinued study medication; however,
efficacy data were available for 424 men. The primary outcome was the
rate of carotid atherosclerotic progression, measured as the linear
slope over annual ultrasound examinations in the average of the maximum
carotid intima-media thickness (IMT) of the far wall of up to four
arterial segments (the right and left distal common carotid
artery and the right and left carotid bulb). For the carotid arteries,
at the overall mean baseline IMT of 1.66 mm, the rate of progression of
carotid atherosclerosis was 45% (95% CI, 16 to 69%)
less in the pravastatin (0.017 mm/y) than the placebo
(0.031 mm/y) group (P=.005). In the common carotid artery
there was a treatment effect of 66% (95% CI, 30 to 95%;
pravastatin 0.010 mm/y; placebo 0.029 mm/y;
P<.002) at the overall mean baseline IMT of 1.35 mm. A
treatment effect of 30% (95% CI, -1% to 54%) was found for the
carotid bulb (pravastatin, 0.028; placebo, 0.040;
P=.056) at the overall mean baseline IMT of 2.0 mm. The
treatment effect was larger in subjects with higher baseline IMT
values, in smokers and in those with low plasma vitamin E levels. There
was no significant treatment effect on atherosclerotic progression in
the femoral arteries.
Conclusions These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers.
Key Words: smoking • lipoproteins • clinical trials • atherosclerosis
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H. Koshiyama, Y. Nakamura, S. Tanaka, and J. Minamikawa Decrease in Carotid Intima-Media Thickness after 1-Year Therapy with Etidronate for Osteopenia Associated with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2793 - 2796. [Abstract] [Full Text]
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P. Sun, K. M. Dwyer, C. N. B. Merz, W. Sun, C. A. Johnson, A. M. Shircore, and J. H. Dwyer Blood Pressure, LDL Cholesterol, and Intima-Media Thickness : A Test of the "Response to Injury" Hypothesis of Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 2005 - 2010. [Abstract] [Full Text] [PDF]
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M. Zureik, P. Ducimetiere, P.-J. Touboul, D. Courbon, C. Bonithon-Kopp, C. Berr, and C. Magne Common Carotid Intima-Media Thickness Predicts Occurrence of Carotid Atherosclerotic Plaques : Longitudinal Results From the Aging Vascular Study (EVA) Study Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1622 - 1629. [Abstract] [Full Text] [PDF]
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L. A. Prosser, A. A. Stinnett, P. A. Goldman, L. W. Williams, M. G.M. Hunink, L. Goldman, and M. C. Weinstein Cost-Effectiveness of Cholesterol-Lowering Therapies according to Selected Patient Characteristics Ann Intern Med, May 16, 2000; 132(10): 769 - 779. [Abstract] [Full Text] [PDF]
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D. Baldassarre, E. Tremoli, M. Amato, F. Veglia, A. Bondioli, and C. R. Sirtori Reproducibility Validation Study Comparing Analog and Digital Imaging Technologies for the Measurement of Intima-Media Thickness Stroke, May 1, 2000; 31(5): 1104 - 1110. [Abstract] [Full Text] [PDF]
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J. C. LaRosa, J. He, and S. Vupputuri Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials JAMA, December 22, 1999; 282(24): 2340 - 2346. [Abstract] [Full Text] [PDF]
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E. R Mohler III, N. Delanty, D. J Rader, and E. C Raps Statins and cerebrovascular disease: plaque attack to prevent brain attack Vascular Medicine, November 1, 1999; 4(4): 269 - 272. [Abstract] [PDF]
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C. Skoglund-Andersson, R. Tang, M. G. Bond, U. de Faire, A. Hamsten, and F. Karpe LDL Particle Size Distribution Is Associated With Carotid Intima-Media Thickness in Healthy 50-Year-Old Men Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2422 - 2430. [Abstract] [Full Text] [PDF]
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P. H. Davis, J. D. Dawson, L. T. Mahoney, and R. M. Lauer Increased Carotid Intimal-Medial Thickness and Coronary Calcification Are Related in Young and Middle-Aged Adults : The Muscatine Study Circulation, August 24, 1999; 100(8): 838 - 842. [Abstract] [Full Text] [PDF]
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S. D. Ross, I. E. Allen, J. E. Connelly, B. M. Korenblat, M. E. Smith, D. Bishop, and D. Luo Clinical Outcomes in Statin Treatment Trials: A Meta-analysis Arch Intern Med, August 9, 1999; 159(15): 1793 - 1802. [Abstract] [Full Text] [PDF]
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T. A. Lakka, R. Salonen, G. A. Kaplan, and J. T. Salonen Blood Pressure and the Progression of Carotid Atherosclerosis in Middle-Aged Men Hypertension, July 1, 1999; 34(1): 51 - 56. [Abstract] [Full Text] [PDF]
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S. Ebrahim, O. Papacosta, P. Whincup, G. Wannamethee, M. Walker, A. N. Nicolaides, S. Dhanjil, M. Griffin, G. Belcaro, A. Rumley, et al. Carotid Plaque, Intima Media Thickness, Cardiovascular Risk Factors, and Prevalent Cardiovascular Disease in Men and Women : The British Regional Heart Study Stroke, April 1, 1999; 30(4): 841 - 850. [Abstract] [Full Text] [PDF]
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H. C. Bucher, L. E. Griffith, and G. H. Guyatt Systematic Review on the Risk and Benefit of Different Cholesterol-Lowering Interventions Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 187 - 195. [Abstract] [Full Text] [PDF]
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R. Rabbani and E. J. Topol Strategies to achieve coronary arterial plaque stabilization Cardiovasc Res, February 1, 1999; 41(2): 402 - 417. [Abstract] [Full Text] [PDF]
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J. F. Plehn, B. R. Davis, F. M. Sacks, J. L. Rouleau, M. A. Pfeffer, V. Bernstein, T. E. Cuddy, L. A. Moye, L. B. Piller, J. Rutherford, et al. Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin : The Cholesterol and Recurrent Events (CARE) Study Circulation, January 19, 1999; 99(2): 216 - 223. [Abstract] [Full Text] [PDF]
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M.-L. M. Gronholdt Ultrasound and Lipoproteins as Predictors of Lipid-Rich, Rupture-Prone Plaques in the Carotid Artery Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 2 - 13. [Abstract] [Full Text] [PDF]
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J. A Papadakis, D. P Mikhailidis, and A. F Winder Lipids and stroke: neglect of a useful preventive measure? Cardiovasc Res, November 1, 1998; 40(2): 265 - 271. [Abstract] [Full Text] [PDF]
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T. A. Jacobson, J. R. Schein, A. Williamson, and C. M. Ballantyne Maximizing the Cost-effectiveness of Lipid-Lowering Therapy Arch Intern Med, October 12, 1998; 158(18): 1977 - 1989. [Abstract] [Full Text] [PDF]
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R. S. Rosenson and C. C. Tangney Antiatherothrombotic Properties of Statins: Implications for Cardiovascular Event Reduction JAMA, May 27, 1998; 279(20): 1643 - 1650. [Abstract] [Full Text] [PDF]
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T. A. Pearson Lipid-Lowering Therapy in Low-Risk Patients JAMA, May 27, 1998; 279(20): 1659 - 1661. [Full Text] [PDF]
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S. MacMahon, N. Sharpe, G. Gamble, H. Hart, J. Scott, J. Simes, and H. White Effects of Lowering Average or Below-Average Cholesterol Levels on the Progression of Carotid Atherosclerosis : Results of the LIPID Atherosclerosis Substudy Circulation, May 19, 1998; 97(18): 1784 - 1790. [Abstract] [Full Text] [PDF]
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R. M. Werner and T. A. Pearson What's So Passive About Passive Smoking?: Secondhand Smoke as a Cause of Atherosclerotic Disease JAMA, January 14, 1998; 279(2): 157 - 158. [Full Text] [PDF]
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T. J. Wilt, H. B. Rubins, S. J. Robins, W. A. Riley, D. Collins, M. Elam, G. Rutan, and J. W. Anderson Carotid Atherosclerosis in Men With Low Levels of HDL Cholesterol Stroke, October 1, 1997; 28(10): 1919 - 1925. [Abstract] [Full Text]
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S. A. Everson, G. A. Kaplan, D. E. Goldberg, R. Salonen, and J. T. Salonen Hopelessness and 4-Year Progression of Carotid Atherosclerosis : The Kuopio Ischemic Heart Disease Risk Factor Study Arterioscler Thromb Vasc Biol, August 1, 1997; 17(8): 1490 - 1495. [Abstract] [Full Text]
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P. R. Hebert, J. M. Gaziano, K. S. Chan, and C. H. Hennekens Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality: An Overview of Randomized Trials JAMA, July 23, 1997; 278(4): 313 - 321. [Abstract] [PDF]
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J. Lynch, N. Krause, G. A. Kaplan, R. Salonen, and J. T. Salonen Workplace Demands, Economic Reward, and Progression of Carotid Atherosclerosis Circulation, July 1, 1997; 96(1): 302 - 307. [Abstract] [Full Text]
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A. M. Gotto Jr Statin Therapy and Reduced Incidence of Stroke: Implications of Cholesterol-Lowering Therapy for Cerebrovascular Disease Arch Intern Med, June 23, 1997; 157(12): 1283 - 1284. [Abstract] [PDF]
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J. R. Crouse III, R. P. Byington, H. M. Hoen, and C. D. Furberg Reductase Inhibitor Monotherapy and Stroke Prevention Arch Intern Med, June 23, 1997; 157(12): 1305 - 1310. [Abstract] [PDF]
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G. J. Blauw, A. M. Lagaay, A. H. M. Smelt, and R. G. J. Westendorp Stroke, Statins, and Cholesterol : A Meta-Analysis of Randomized, Placebo-Controlled, Double-Blind Trials With HMG-CoA Reductase Inhibitors Stroke, May 1, 1997; 28(5): 946 - 950. [Abstract] [Full Text]
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J. Lynch, G. A. Kaplan, R. Salonen, and J. T. Salonen Socioeconomic Status and Progression of Carotid Atherosclerosis : Prospective Evidence From the Kuopio Ischemic Heart Disease Risk Factor Study Arterioscler Thromb Vasc Biol, March 1, 1997; 17(3): 513 - 519. [Abstract] [Full Text]
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J. T. Salonen, K. Nyyssonen, R. Salonen, E. Porkkala-Sarataho, T.-P. Tuomainen, U. Diczfalusy, and I. Bjorkhem Lipoprotein Oxidation and Progression of Carotid Atherosclerosis Circulation, February 18, 1997; 95(4): 840 - 845. [Abstract] [Full Text]
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