Despite significant improvements in the survival of patients with atherosclerotic cardiovascular disease, atherosclerotic coronary heart disease (ACHD) remains the leading cause of mortality and morbidity in the United States and the western world. The results of the initial phase of the Program on the Surgical Control of the Hyperlipidemias (POSCH), a prospective, randomized, controlled, secondary atherosclerosis intervention trial have provided the strongest evidence to-date of the benefits of lipid modification in hypercholesterolemic patients with ACHD. In the intervention group (partial ileal bypass group), total cholesterol was 23.3% lower, LDL cholesterol was 37.7% lower, and HDL cholesterol was 4.3% higher than in the diet-treated control group. A 22% lower overall mortality was observed with a mean follow-up of 9.7 years, with a 36% lower overall mortality in patients with a normal left ventricular ejection fraction (equal to or greater than 50%). A 35% reduction in ACHD mortality or confirmed nonfatal myocardial infarction was noted in the intervention group. There was a 27% reduction in the clinical development of peripheral vascular disease and a 61% reduction in the performance of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty in the intervention group. All the endpoint findings were statistically significant (p is less than 0.05 to p less than 0.001) at the time of publication of the initial POSCH results (N Engl J Med 1990; 323:946-55) except those for overall mortality (p=O.164) and ACHD mortality (p=O.133). Thus, the effect of lipid lowering on overall mortality and ACHD mortality as a single endpoint, remains unconfirmed in the current clinical trial experience. In this proposal, long-term follow-up of the surviving members of the POSCH control and intervention groups by detailed direct patient contact is planned. These data, acquired in a scientifically reliable fashion at relatively minimal cost, will permit ongoing statistical comparison of the differences in long-term mortality and morbidity between the POSCH control and intervention groups. In addition, continuing assessment of the history of ACHD in patients treated with diet therapy alone will be possible in the control group. Long-term evaluation of any adverse consequences of aggressive lipid-lowering in general, and in particular by partial ileal bypass, will be possible with ongoing follow-up of the intervention group. Albeit small in number, the female POSCH participants present an opportunity for continuing assessment of the mortality and morbidity results of aggressive lipid intervention in women which may provide unique information currently lacking and demanded by the scientific community and the public. Finally, the establishment and maintenance of the POSCH arteriography library will allow for examination of the relationship of the serial coronary arteriographic results in POSCH to the long-term mortality and morbidity experience.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL049522-03S1
Application #
2329403
Study Section
Special Emphasis Panel (ZHL1-CCT-A (01))
Project Start
1993-01-01
Project End
1997-12-31
Budget Start
1995-01-01
Budget End
1996-12-31
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Surgery
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Buchwald, Henry; Rudser, Kyle D; Williams, Stanley E et al. (2010) Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias. Ann Surg 251:1034-40
Buchwald, Henry; Williams, Stanley E; Matts, John P et al. (2002) Overall mortality in the program on the surgical control of the hyperlipidemias. J Am Coll Surg 195:327-31
Buchwald, Henry; Williams, Stanley E; Matts, John P et al. (2002) Lipid modulation and liver function tests. A report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). J Cardiovasc Risk 9:83-7
Buchwald, H; Boen, J R; Nguyen, P A et al. (2001) Plasma lipids and cardiovascular risk: a POSCH report. Program on the Surgical Control of the Hyperlipidemias. Atherosclerosis 154:221-7
Buchwald, H; Varco, R L; Boen, J R et al. (1998) Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias. Arch Intern Med 158:1253-61
Buchwald, H; Hunter, D W; Tuna, N et al. (1998) Myocardial infarction and percent arteriographic stenosis of culprit lesion: report from the Program on the Surgical Control of the Hyperlipidemias (POSCH). Atherosclerosis 138:391-401
Buchwald, H; Campos, C T; Boen, J R et al. (1996) Gender-based mortality follow-up from the Program on the Surgical Control of the Hyperlipidemias (POSCH) and meta-analysis of lipid intervention trials. Women in POSCH and other lipid trials. Ann Surg 224:486-98;discussion 498-500
Buchwald, H; Bourdages, H R; Campos, C T et al. (1996) Impact of cholesterol reduction on peripheral arterial disease in the Program on the Surgical Control of the Hyperlipidemias (POSCH). Surgery 120:672-9
Fitch, L L; Buchwald, H; Matts, J P et al. (1995) Effect of aspirin use on death and recurrent myocardial infarction in current and former cigarette smokers. Program on the Surgical Control of the Hyperlipidemias Group. Am Heart J 129:656-62
Buchwald, H; Campos, C T (1995) Program on the surgical control of the hyperlipidemias: 1994 report. J Cardiovasc Pharmacol 25 Suppl 4:S3-10

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