The objective of this study was to assess the percent stenosis of the culprit lesion responsible for subsequent myocardial infarction in the Program on the Surgical Control of the Hyperlipidemias (POSCH). It is unknown if the susceptible coronary artery culprit lesion responsible for an acute myocardial infarction is relatively large (≥50% arteriographic stenosis) and hemodynamically significant (≥70% stenosis), or small (<50% stenosis) and asymptomatic. Certain necropsy and arteriography studies support the large progenitor lesion concept, and other arteriography studies support the small lesion hypothesis. We analyzed the coronary arteriogram immediately preceding a Q wave (transmural) myocardial infarction for the degree of stenosis of the suspected culprit lesion, which was selected by visual inspection of the coronary circulation supplying the electrocardiogram-defined area of myocardial infarction. There was no perceptible difference with respect to vessel segment distribution of culprit lesions or time to infarction between the 52 control-group patients and the 27 intervention-group patients. For the two groups combined (n=79), the predominantly involved segments were the middle right coronary artery and the proximal left anterior descending coronary artery. The time interval from the preceding coronary arteriogram closest to the index myocardial infarction ranged from 0 days to 10 years; however, 64.6% of the arteriograms were performed 2 years or less prior to the myocardial infarction. Only 5.1% of the patients in both groups combined had a culprit lesion stenosis <50%, while 88.6% of the patients in both groups combined had a culprit lesion stenosis ≥70%. The results strongly favor the large lesion hypothesis of causation for myocardial infarction. It is premature, however, to state that the relative size of the culprit lesion has been indisputably determined. The resolution of this problem has exceedingly important practical implications for the management of patients with known atherosclerotic coronary heart disease and for those asymptomatic individuals with silent atherosclerotic coronary heart disease.

BACKGROUND:In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance.METHODS:The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years).RESULTS:At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up.CONCLUSION:At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

The pathophysiology of the atherosclerotic plaque consists of the interaction of four cell types (T lymphocytes, macrophages, smooth muscle cells and endothelial cells), several processes (notably low density lipoprotein oxidation and inflammation), and numerous attractant, agonist and antagonist factors. The most recent conceptualization of the pathophysiology of atherosclerosis emphasizes that the clinically dangerous lesions are not necessarily the largest or most stenotic plaques but seem to be the smaller plaques, rich in lipids. Thus, lipid intervention trials test not only the benefits of risk factor modification, but assess the direct benefits of converting active plaques, with thin caps, rich in lipids, and susceptible to fissuring and acute thrombosis, into stable plaques with a reduced lipid content and a thicker more fibrous cap.

BACKGROUND:Few lipid/atherosclerosis intervention trials have assessed the impact of cholesterol reduction on peripheral arterial disease. The 838 patients evaluated in the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial represent more than the total number of patients in the seven previously reported studies.METHODS:Peripheral arterial disease in POSCH was assessed by progression of clinical disease, serial changes in the systolic blood pressure ankle/brachial index (ABI), and changes on sequential peripheral arteriograms.RESULTS:At the time of formal closure of the POSCH trial on July 19, 1990, claudication or limb-threatening ischemia was exhibited in 72 of 417 control group (CG) patients and in 54 of 421 intervention group (IG) patients (IG relative risk [RR] 0.702, 95% confidence interval [CI] 0.169 to 1.000, p = 0.049). With additional follow-up evaluation to September 30, 1994, clinical peripheral arterial disease was evident in 91 CG patients and 64 IG patients (RR 0.656, 95% CI 0.200 to 0.903, p = 0.009). At the 5-year follow-up evaluation, an ABI of less than 0.95 was present in 41 of 120 CG patients and in 24 of 126 IG patients, all of whom had an ABI of 0.95 or greater at baseline (RR in the IG of 0.557, 95% CI 0.360 to 0.863, p < 0.01). No appreciable differences were noted in the progression or regression of arteriographic peripheral arterial disease between the two groups.CONCLUSIONS:Effective cholesterol reduction in POSCH led to statistically significant differences between the control and the intervention groups in the development of clinically evident peripheral arterial disease and in the ABI values, but not in the peripheral arteriograms. Additional studies need to assess the correlation between peripheral arterial changes and coronary arterial changes and clinical atherosclerosis events. Intervention trials that study peripheral arterial disease have intrinsic value in the evaluation of the impact of risk factor modification on progression of atherosclerotic peripheral arterial disease.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ileal bypass surgery as the intervention modality. For this report, we analyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as those with: (1) an absolute z-value > or = 2.0 for the subgroup, if the absolute z-value for the overall effect was < 2.0; and (2) an absolute z-value > or = 3.0 for the subgroup and a relative risk < or = 0.5, if the absolute z-value for the overall effect was > or = 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found seven subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups for more than one endpoint, there were 13 individual subgroups with differential effects. Of these, seven demonstrated internal consistency across endpoints, and five of these seven displaced external consistency with known ACHD risk factors and for biological plausibility: triglyceride concentration > or = 200 mg/dl; cigarette smoking; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the overall treatment effect, by the reduction of a single risk factor, hypercholesterolemia, in patients with at least two major ACHD risk factors was a provocative and an hypothesis-generating outcome of this analysis. The clinical implications of this finding may lead to more aggressive cholesterol intervention in patients with multiple ACHD risk factors.

The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, tested the hypothesis that cholesterol modification induced by partial ileal bypass would favorably affect mortality and morbidity due to coronary heart disease (CHD). The study population consisted of 838 patients (417 in the control group and 421 in the surgery group) in four clinical centers, both men (90.7%) and women with an average age of 51 years who had survived a first myocardial infarction. The lipid changes in POSCH have been the most marked in any atherosclerosis intervention trial utilizing a single mode of intervention in addition to diet therapy. At 5 years, the surgery group, compared with the control group, had a 23.3 +/- 1.0% (mean +/- SE) lower total plasma cholesterol level (p < 0.0001), a 37.7 +/- 1.2% lower low-density lipoprotein cholesterol level (p < 0.0001), and a 4.3 +/- 1.8% higher high-density lipoprotein cholesterol level (p = 0.02). For the combined end point of CHD mortality and confirmed nonfatal myocardial infarction, there was a 35.0% reduction in the surgery group (p < 0.001). Coronary artery bypass grafting was reduced in the surgery group by 62.0% (p < 0.0001) and percutaneous transluminal coronary angioplasty was reduced by 55.0% (p < 0.01). A comparison of baseline coronary arteriograms with those obtained at 3, 5, 7, and, 10 years consistently showed less atherosclerosis disease progression (p < 0.001) and greater atherosclerosis disease regression at 5 and 7 years (p < 0.01)in the surgery group. At formal trial completion in July 1990, the overall mortality in the surgery subgroup with an ejection fraction of 50% or greater was 36.1% lower (p = 0.02). During subsequent follow-up, trends toward statistical significance for differences in both CHD and in overall mortality have become evident. The POSCH results provide strong support for beneficial clinical and arteriographic reduction of atherosclerosis progression after lipid modification by partial ileal bypass.

The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nonfatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.2 to 5.1, p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives. We sought to analyze the disease free intervals and calculate the freedom from atherosclerosis events in the Program on the Surgical Control of the Hyperlipidemias (POSCH).Background. The POSCH study was a randomized, secondary lipid/atherosclerosis intervention trial that provided strong evidence for reduction in atherosclerosis progression as demonstrated by clinical and arteriographic end points. The 417 control group patients received American Heart Association phase II diet instruction, and the 421 intervention group patients received identical dietary instruction and underwent a partial ileal bypass operation.Methods. Four outcome measures were determined: 1) overall mortality, 2) coronary heart disease mortality, 3) coronary heart disease mortality and confirmed nonfatal myocardial infarction, and 4) coronary/cardiac interventions.Results. An overall mortality rate of 10% occurred at 6.7 years in the control group and 9.4 years in the intervention group, for a gain in disease-free interval of 2.7 years in the intervention group (p = 0.032). A coronary heart disease mortality rate of 8% occurred at 7.2 years in the control group and 11 years in the intervention group, for a gain of 3.8 years (p = 0.046). Twenty percent of patients demonstrated the combined end point of coronary heart disease mortality and confirmed nonfatal myocardial infarction at 5.9 years in the control group and 11.4 years in the intervention group, for a gain of 5.5 years (p < 0.001). Twenty-five percent of patients underwent either coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty or heart transplantation at 5.4 years in the control group and 12.4 years in the intervention group, for a gain of 7 years (p < 0.001).Conclusions. The marked lipid modification achieved by partial ileal bypass in the POSCH trial led to demonstrable increases in the disease-free intervals for overall mortality, coronary heart disease mortality, coronary heart disease mortality and confirmed nonfatal myocardial infarction, and coronary intervention procedures. For the clinician and the patient, estimation of disease-free intervals may be more relevant than assessment of differences in incidence rates and risk ratios.

Annals of the New York Academy of SciencesVolume 748, Issue 1 p. 342-354 Control of Risk Factors in Atherosclerosis POSCH Reporta HENRY BUCHWALD, HENRY BUCHWALD bDepartment of Surgery University of Minnesota Medical School Box 290 UMHC Minneapolis, Minnesota 55455Search for more papers by this authorCHRISTIAN T. CAMPOS, CHRISTIAN T. CAMPOS cDivision of Cardiothoracic Surgery New England Deaconess Hospital and Harvard Medical School Boston, MassachusettsSearch for more papers by this author HENRY BUCHWALD, HENRY BUCHWALD bDepartment of Surgery University of Minnesota Medical School Box 290 UMHC Minneapolis, Minnesota 55455Search for more papers by this authorCHRISTIAN T. CAMPOS, CHRISTIAN T. CAMPOS cDivision of Cardiothoracic Surgery New England Deaconess Hospital and Harvard Medical School Boston, MassachusettsSearch for more papers by this author First published: January 1994 https://doi.org/10.1111/j.1749-6632.1994.tb17331.x a Supported by Grants RO1-HL-15265 and R01-HL-49522 from the National Heart, Lung, and Blood Institute and by a Minnesota State Special Legislative Appropriation. d A complete list of the participants in this research study appears in the Appendix. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume748, Issue1Atherosclerosis III: Recent Advances in Atherosclerosis ResearchJanuary 1994Pages 342-354 RelatedInformation

BACKGROUND:Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population.METHODS:The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed.RESULTS:The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%.CONCLUSIONS:These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.

Thirty-five patients who had undergone primary bariatric surgery between 14 January 1988 and 16 September 1990 were selected for retrospective analysis based on the availability of 3-month and 1-year (±3 months) follow-up visit records. Fourteen patients had undergone a Roux- en-Y gastric bypass (RGB), and 21 patients had undergone a Silastic® ring vertical gastroplasty (SRVG). Weight loss, pre- and postoperative body mass index (BMI), and the postoperative incidence of dumping syndrome, anemia, and food intolerance were compared. At 1 year (±3 months), the average weight loss was 40 kg for the entire group. The RGB patients lost an average of 41.7 kg, while the SRVG patients lost an average of 39.4 kg (not significant). The average preoperative BMI was 46.4 kg/m2 for both the RGB and SRVG patients. The 1-year postoperative BMI was 30.6 kg/m2 for the RGB patients and 32.4 kg/m2 for the SRVG patients (not significant). One RGB patient developed a dumping syndrome, and one RGB patient showed evidence of a nutritional anemia. Neither complication was incapacitating. The SRVG patients had far more difficulty in advancing the consistency and variety of their diet in the early postoperative period, with only 62% (13/21) of the SRVG patients demonstrating an ability to tolerate a regular consistency diet at the end of 1 year. Seventy-six percent (16/21) of the SRVG patients reported occasional vomiting at 1 year, compared to only 7% (1/14) of the RGB patients. This retrospective analysis documented comparable weight loss for the RGB and SRVG operations. A greater incidence of eating problems up to 1 year postoperatively was observed in patients following SRVG in comparison to RGB.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.