George Sopko

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background— The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results— Outcome data were analyzed by intention to treat; the Kaplan–Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group. Conclusions— In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

The effects of exercise and weight loss on plasma lipids in young obese men

We studied the independent and combined effects of exercise training and weight loss on blood lipids under fixed diet and exercise conditions. Twenty-one obese sedentary men were randomly allocated to one of four treatment groups: (1) inactive and constant weight (control), (2) exercise training and constant weight, (3) inactive and weight loss, and (4) exercise training and weight loss. There were three study periods: a 3 week baseline period inactive and on an isocaloric diet, a 12 week treatment period, and a 3 week weight stabilization period. Exercise consisted of treadmill walking at an energy cost of 3500 kcal/wk for groups 2 and 4 with replacement caloric intake only in group 2. Group 3 reduced caloric intake by 3500 kcal/wk during the treatment period. Weight loss for groups 3 and 4 were 13.4 pounds and 13.7 pounds, respectively. Maximal oxygen uptake (mL/min) increased 6% in both exercise groups (2 and 4), and percent body fat decreased only in these groups. Regression analysis by group assignment on HDL cholesterol (HDL-C) showed that the inactivity-weight loss modality (group 3) and the exercise-constant weight modality (group 2) each significantly increased HDL-C, with an additive effect of exercise and weight loss (group 4). The rate of HDL-C change differed significantly between groups (P = 0.01). HDL-C increased 0.63, 0.61, and 1.89 mg/dL per 3 weeks or 2%, 2.4%, and 5.5% above baseline levels in groups 2, 3, and 4, respectively, while the control group decreased 0.11 mg/dL. Plasma triglycerides and very low-density lipoprotein (VLDL) cholesterol increased with exercise at constant weight (group 2) and decreased with exercise associated with weight loss (group 4). In conclusion, exercise and weight loss separately and independently increase HDL-C, and their effects are additive.

Combined α/β-blockade versus β1-selective blockade in essential hypertension in black and white patients

The purpose of this multicenter investigation was to determine the efficacy and safety of the α/β‐blocker labetalol versus the β1‐selective β‐blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety‐two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (−12/ −13 mm Hg, respectively) compared with atenolol (−7/ −9 mm Hg; p < 0.05; p < 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the α1‐blocking property of labetalol provides an additional lowering of the blood pressure over that seen with β1‐blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.

Renin-angiotensin and sympathetic nervous system activity in grade school children.

Renin-angiotensin and sympathetic nervous system activity were evaluated in grade school children selected from the upper 0.26% and lower 5% of the blood pressure distribution constructed from a survey in the Minneapolis Public Schools. Eleven children from the upper 0.26% group and 19 children from the lower 5% group were admitted to the Clinical Research Center for 5 days and maintained on a 110 mEq sodium and 75 mEq potassium diet. On the fifth hospital day blood samples were obtained supine, after 2 hours of upright posture and after treadmill exercise. Mean sodium and potassium excretion and serum sodium and potassium were similar between the two groups. Plasma norepinephrine was not significantly different between the two groups at any of the three sampling times. Plasma renin activity was significantly lower in the upper 0.26% group in the supine and 2-hour upright samples. Mean plasma aldosterone (measured only in the supine blood samples) was not significantly different between groups. Plasma aldosterone values were significantly correlated with plasma renin activity only in the lower 5% group (r = 0.67, p < 0.005). This study suggests that in grade school children sympathetic nervous system activity is similar between children with high and low blood pressure but that plasma renin activity is lower and an apparent dissociation between plasma aldosterone and renin activity exists in the high blood pressure group. These findings should be confirmed in studies with larger numbers of subjects selected from the entire distribution of blood pressure. (Hypertension 4: 299–306, 1982)

Controlled trial of acifran in type II hyperlipoproteinemia.

The hypolipidemic effects of acifran were evaluated in a randomized, double‐blind, placebo‐controlled study of 30 patients with type IIa hyperlipoproteinemia. Plasma lipid and lipoprotein values were determined at baseline (mean of three values), again after a 2‐week single‐blind period of acifran dosing, and at 2‐week intervals during a 10‐week period of double‐blind drug dosing. At week 8, subjects who received the lower dose of acifran (100 mg t.i.d.) showed significantly lower levels of total and low‐density lipoprotein cholesterol and triglycerides compared with their baseline levels (P < 0.01) or the placebo group (P < 0.05). At week 12, subjects who received the higher dose of acifran (300 mg t.i.d.) had an increase in high‐density lipoprotein levels of 16% (P < 0.01) and a decrease in the ratio of low‐ to high‐density lipoproteins of 22% compared with their baseline levels (P < 0.01). There were no significant differences in lipid responses between the two groups receiving acifran. Transient mild flushing and pruritus were experienced by some subjects, but no subject failed to complete the study because of drug intolerance or side effects. The safety and efficacy demonstrated in this short‐term therapeutic trial justify additional long‐term studies with acifran.

Effects on blood lipids and body weight in high risk men of a practical exercise program

The effects of moderate exercise on serum total cholesterol (TC), high density (HDL-C), low density (LDL-C), and very low density (VLDL-C) lipoprotein cholesterol fractions, triglycerides (TG), body weight (BW) and skinfolds (SF) were studied during a 12-week period among 23 sedentary middle-aged men. The results show that regular exercise in men eating a fat-modified diet alters in a favorable direction body fat, weight and lipoprotein fractions. Weight loss with exercise significantly increased HDL-C (P = 0.01), although this increase in HDL-C occurred after a latency period of at least 6 weeks and an average weight loss of at least 4 lbs. The amount of exercise effective in risk factor reduction is within the capacity of most middle-aged men.