Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

ContextAbout 5% of the US population is morbidly obese. This disease remains
largely refractory to diet and drug therapy, but generally responds well to
bariatric surgery.ObjectiveTo determine the impact of bariatric surgery on weight loss, operative
mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia,
hypertension, and obstructive sleep apnea).Data Sources and Study SelectionElectronic literature search of MEDLINE, Current Contents, and the Cochrane
Library databases plus manual reference checks of all articles on bariatric
surgery published in the English language between 1990 and 2003. Two levels
of screening were used on 2738 citations.Data ExtractionA total of 136 fully extracted studies, which included 91 overlapping
patient populations (kin studies), were included for a total of 22 094
patients. Nineteen percent of the patients were men and 72.6% were women,
with a mean age of 39 years (range, 16-64 years). Sex was not reported for
1537 patients (8%). The baseline mean body mass index for 16 944 patients
was 46.9 (range, 32.3-68.8).Data SynthesisA random effects model was used in the meta-analysis. The mean (95%
confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%)
for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding;
61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and
70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative
mortality (≤30 days) in the extracted studies was 0.1% for the purely restrictive
procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion
or duodenal switch. Diabetes was completely resolved in 76.8% of patients
and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more
of patients. Hypertension was resolved in 61.7% of patients and resolved or
improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients
and was resolved or improved in 83.6% of patients.ConclusionsEffective weight loss was achieved in morbidly obese patients after
undergoing bariatric surgery. A substantial majority of patients with diabetes,
hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete
resolution or improvement.

https://jamanetwork.com/journals/jama/articlepdf/199587/JRV40082.pdf

Bariatric surgery: a systematic review and meta-analysis.

Context.—Observational studies have found lower rates of coronary heart disease
(CHD) in postmenopausal women who take estrogen than in women who do not,
but this potential benefit has not been confirmed in clinical trials.Objective.—To determine if estrogen plus progestin therapy alters the risk for
CHD events in postmenopausal women with established coronary disease.Design.—Randomized, blinded, placebo-controlled secondary prevention trial.Setting.—Outpatient and community settings at 20 US clinical centers.Participants.—A total of 2763 women with coronary disease, younger than 80 years,
and postmenopausal with an intact uterus. Mean age was 66.7 years.Intervention.—Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone
acetate in 1 tablet daily (n=1380) or a placebo of identical appearance (n=1383).
Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were
taking it at the end of 1 year, and 75% at the end of 3 years.Main Outcome Measures.—The primary outcome was the occurrence of nonfatal myocardial infarction
(MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization,
unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke
or transient ischemic attack, and peripheral arterial disease. All-cause mortality
was also considered.Results.—Overall, there were no significant differences between groups in the
primary outcome or in any of the secondary cardiovascular outcomes: 172 women
in the hormone group and 176 women in the placebo group had MI or CHD death
(relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The
lack of an overall effect occurred despite a net 11% lower low-density lipoprotein
cholesterol level and 10% higher high-density lipoprotein cholesterol level
in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically
significant time trend, with more CHD events in the hormone group than in
the placebo group in year 1 and fewer in years 4 and 5. More women in the
hormone group than in the placebo group experienced venous thromboembolic
events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84
vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences
in several other end points for which power was limited, including fracture,
cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).Conclusions.—During an average follow-up of 4.1 years, treatment with oral conjugated
equine estrogen plus medroxyprogesterone acetate did not reduce the overall
rate of CHD events in postmenopausal women with established coronary disease.
The treatment did increase the rate of thromboembolic events and gallbladder
disease. Based on the finding of no overall cardiovascular benefit and a pattern
of early increase in risk of CHD events, we do not recommend starting this
treatment for the purpose of secondary prevention of CHD. However, given the
favorable pattern of CHD events after several years of therapy, it could be
appropriate for women already receiving this treatment to continue.

https://jamanetwork.com/journals/jama/articlepdf/187879/JOC80678.pdf

Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women

BackgroundEvolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. MethodsWe conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. ResultsAt 48 weeks, the ...

/pdf/evolocumab-and-clinical-outcomes-in-patients-with-288ao7yhy6.pdf

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease

IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199201233260406?articleTools=true

The pathogenesis of coronary artery disease and the acute coronary syndromes (1).

Background and Methods The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. Results When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71±0.91 vs. 6.14±0.89 mmol per liter [mean ±SD]; P<0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68±0.78 vs. 4.30±0.89 mmol per liter; P<0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08±0.26 vs. 1.04±0.25 mmol per liter; P = 0.02). Overall mortality...

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)

Correlation of coronary with peripheral arterial stenosis

Positive and negative exercise test results with and without exercise-induced angina in patients with one healed myocardial infarction : analysis of baseline variables and long-term prognosis

James N. Karnegis

Papers

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)

Correlation of coronary with peripheral arterial stenosis

Positive and negative exercise test results with and without exercise-induced angina in patients with one healed myocardial infarction : analysis of baseline variables and long-term prognosis

Directional ST segment deviation in graded exercise tests correlated with left ventricular segmental wall motion