Carotid artery vasoreactivity in response to sympathetic stress correlates with coronary disease risk and is independent of wall thickness.

OBJECTIVES: We designed a study to determine the carotid artery (CA) response to sympathetic activity and to determine whether the response correlates with coronary risk and is independent of wall thickness (IMT). BACKGROUND: Brachial artery reactivity in response to wall stress correlates with coronary risk and coronary disease (CAD). The reactivity of the CA, which is susceptible to atherosclerosis, has not been evaluated. METHODS: The change in diameter of the CA (deltaCAdiam) during a cold pressor test and after nitroglycerin and IMT were measured with ultrasound in 93 men and women at average risk, high risk and with CAD. RESULTS: At 90 s during a cold pressor test average-risk subjects increased CAdiam by 7.9+/-3.3%, which was significantly less in the high-risk group (1.5+/-1.8%), and vasoconstriction occurred in the group of subjects with CAD (-6.9+/-2.7%) (p < 0.01 for comparisons). There were no differences in response to nitroglycerin. Coronary risk was an independent predictor of the %deltaCAdiam (p < 0.0001). Wall thickness, age, systolic pressure and triglycerides each correlated negatively, and high-density lipoprotein cholesterol correlated positively with %deltaCAdiam. The major variable associated with the %deltaCAdiam, was group (p = 0.0001). After adjusting for smoking, age and high-density lipoprotein cholesterol, there was no association between the %deltaCAdiam, and IMT and %deltaCAdiam, but not IMT, was predictive of groups. CONCLUSIONS: The CA response to a sympathetic stimulus is altered in the presence of coronary risk factors and CAD and appears to reflect endothelial function independent of IMT. Carotid artery reactivity may be a valuable adjunctive noninvasive method to assess coronary risk.

Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine.

OBJECTIVES: The purpose of this study was to assess the utility of inhaled nitric oxide (NO), a selective pulmonary vasodilator, for predicting the safety and acute hemodynamic response to high-dose oral nifedipine in primary pulmonary hypertension (PPH). BACKGROUND: A significant decrease in pulmonary vascular resistance with an oral nifedipine challenge is predictive of an improved prognosis, and potential clinical efficacy in PPH. However, the required nifedipine trial carries significant first-dose risk of hypotension. While inhaled NO has been recommended for assessing pulmonary vasodilator reserve in PPH, it is not known whether it predicts the response to nifedipine. METHODS: Seventeen patients with PPH undergoing a nifedipine trial were assessed for hemodynamic response to inhaled NO at 80 parts per million for 5 minutes. The nifedipine trial consisted of 20 mg of nifedipine hourly for 8 hours unless limited by hypotension or intolerable side effects. Patients were classified as responders and nonresponders with positive response defined as > or =20% reduction in mean pulmonary artery pressure (mPA) or pulmonary vascular resistance (PVR) with the vasodilator administration. RESULTS: NO was safely administered to all participants. Seven of 17 (41.2%) responded to NO, and 8 of the 17 to nifedipine (47.1%). Nifedipine was safely administered in 14 of the 17. Three suffered either mild or severe hypotension, including one death. All NO responders also responded to nifedipine, and 9 of the 10 NO nonresponders were nifedipine nonresponders, representing a sensitivity of 87.5%, specificity of 100%, and overall predictive accuracy of 94%. All NO responders tolerated a full nifedipine trial without hypotension. There was a highly significant correlation between the effects of NO and nifedipine on PVR (r=0.67, p=0.003). CONCLUSIONS: The pulmonary vascular response to inhaled NO accurately predicts the acute hemodynamic response to nifedipine in PPH, and a positive response to NO is associated with a safe nifedipine trial. In patients comparable with those evaluated, a trial of nifedipine in NO nonresponders appears unwarranted and potentially dangerous.

Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension.

OBJECTIVES: The aim of this study was to explore the full range of tricuspid valve regurgitation velocity (TRV) at rest and with exercise in disease free individuals. Additionally we examined the relationship of stroke volume (SV), cardiac output (CO) and TRV to exercise capacity. BACKGROUND: Doppler evaluation of TRV can be used to estimate pulmonary artery systolic pressure (PASP). Most studies have assumed TRV < or = 2.5 m/s as the upper limits of normal. The full range of TRV with exercise has been incompletely defined. METHODS: Highly conditioned athletes (n = 26) and healthy, active, young male volunteers (n = 14) underwent standardized recumbent bicycle exercise. Exercise parameters included: TRV, SV, CO, systolic (SBP) and diastolic (DBP) systemic blood pressure. RESULTS: Tricuspid valve regurgitation, SV, HR and CO were significantly higher in athletes than in nonathletes over all workloads, including rest. Systolic blood pressure and DBP did not show significant differences between the two groups. CONCLUSIONS: This study defines the upper physiologic limits of TRV at rest and during exercise in normals and provides a noninvasive standard for the diagnosis of pulmonary hypertension.

Intraaortic balloon pump insertion: a randomized study comparing percutaneous and surgical techniques.

To compare the percutaneous and surgical techniques of intraaortic balloon pump insertion, 101 patients referred for this procedure were randomly assigned to either percutaneous or surgical insertion. Insertion using the designated technique was successful in 45 (88%) of 51 patients with percutaneous insertion and 48 (96%) of 50 patients with surgical insertion (difference not statistically significant). The time from the beginning of the insertion procedure to the initiation of counterpulsation was 13 +/- 8 minutes for the percutaneous technique versus 31 +/- 16 minutes for the surgical technique (p less than 0.001). In the percutaneous group, 10 patients required Fogarty thrombectomy after balloon pump removal, and 1 patient developed severe leg ischemia requiring immediate termination of balloon pump support. In the surgical group, one patient developed leg ischemia requiring surgical intervention, three patients developed sepsis with bacteremia (including one patient who required vein patch repair of the femoral artery), one patient developed a wound infection requiring debridement and one patient had a cerebral embolus. Aortic dissection, aortoiliac perforation or amputation did not occur in either group. Major vascular complications occurred in 11 patients (22%) with percutaneous insertion versus 2 patients (4%) with surgical insertion (p less than 0.05). It is concluded that although the percutaneous technique for intraaortic balloon pump insertion is faster than the surgical technique and is technically easy, it is associated with a higher incidence of vascular complications.

Antioxidant nutrient supplementation reduces the susceptibility of low density lipoprotein to oxidation in patients with coronary artery disease.

OBJECTIVE: This study sought to determine the effect of antioxidant supplementation on the susceptibility of low density lipoprotein (LDL) to oxidation in patients with established cardiovascular disease (CVD). BACKGROUND: Data are inconsistent regarding the role of antioxidant nutrients in the prevention of CVD. METHODS: The study design was a 12-week, double-blind, placebo-controlled clinical trial. Patients with CVD (n = 45) were randomized to 1) placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta-carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week measurements of lipoproteins and lag phase were obtained. Plasma levels of antioxidants were measured at baseline and 12 weeks. RESULTS: Concentrations of alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid- and high dose groups during the trial. Lag phase significantly increased from baseline (190.1 +/- 63.8 min [mean +/- SD]) to 12 weeks (391.1 +/- 153.0 min) in the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid-dose group was observed during the same time interval. A dose response was found for mean percent change from baseline to 12 weeks for lag phase for the placebo, mid- and high dose groups (p = 0.004 for trend). CONCLUSIONS: A high dose combination of antioxidant nutrients reduces the susceptibility of LDL to oxidation in patients with CVD and may be useful in secondary prevention.

Hydralazine therapy in severe chronic heart failure: inability of radionuclide left ventricular ejection fraction measurement to predict the hemodynamic response.

Simultaneous hemodynamic and radionuclide angiographic assessment was made at rest and during exercise in nine patients with severe chronic congestive heart failure to determine the value of radionuclide left ventricular ejection fraction measurement in predicting the hemodynamic response to short-term treatment with oral hydralazine. Hydralazine, 50 to 100 mg orally every 6 hours, produced significant increases in cardiac index and stroke volume index at rest and during exercise (p less than 0.01) and in left ventricular stroke work index at rest (p less than 0.01) and during exercise (p less than 0.05), significant decreases in systemic vascular resistance at rest and during exercise (p less than 0.01) and significant increases in radionuclide angiographic left ventricular ejection fraction at rest (control 0.21 +/- 0.06 vs. hydralazine 0.26 +/- 0.07, p less than 0.01) and during exercise (control 0.21 +/- 0.08 vs. hydralazine 0.24 +/- 0.09, p less than 0.05). However, there were no statistically significant correlations between changes in radionuclide ejection fraction with hydralazine and changes in hemodynamic variables with hydralazine, either at rest or during exercise. Patients responding hemodynamically to hydralazine could not be separated from those not responding on the basis of the radionuclide ejection fraction at rest or changes in ejection fraction with hydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)

The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

Secondary pulmonary hypertension--diagnosis and management.

Secondary pulmonary hypertension (SPHtn) is generally attributable to abnormalities in structure or function of the heart or lung parenchyma. While often defined as a physiologic parameter, pulmonary hypertension (PHtn) can be a major contributor to death and disability in cardiopulmonary diseases. Both detection and management are a challenge. We will review the pathophysiology, diagnostic tools, and treatment strategies in SPHtn with an emphasis on cor pulmonale associated with chronic obstructive pulmonary disease (COPD), pulmonary vasculopathies, and pulmonary embolus. The pathophysiology and common etiologies of SPHtn can be divided into three major categories: (1) elevated pulmonary venous pressure (LV failure and mitral valve disease), (2) pulmonary vascular occlusive disease with or without pulmonary parenchymal disease (pulmonary emboli, COPD, connective tissue diseases), and (3) hypoxemia (sleep apnea). The echo-Doppler is a simple cost-effective tool for detecting PHtn, evaluating right ventricular function, and distinguishing common etiologies such as abnormal systolic and diastolic left ventricular function and mitral valve disease. The ventilation-perfusion radionuclide scan can be used to exclude thromboembolic PHtn, but a helical computer tomography with contrast or pulmonary angiography are necessary to distinguish patients that may benefit from a pulmonary thromboendarterectomy. The six minute walk oxygen saturation test is useful as a quantitative measure of functional capacity, prognosis, response to therapy, and oxygen requirement. Treatment strategies in cor pulmonale are tailored to the specific diagnosis, but generally include proper nutrition, exercise, oxygen supplementation, medications such as digoxin, diuretics, anti-coagulation, and pulmonary vasodilator therapy in selected patients.

The effect of pravastatin on plasma lipoprotein and apolipoprotein levels in primary hypercholesterolemia. The Southeastern Michigan Collaborative Group.

Pravastatin is a metabolic product of mevastatin and a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It was investigated for its cholesterol-lowering properties in a double-blind, placebo-controlled, multicenter study of 82 patients with primary hypercholesterolemia. Following a 6- to 8-week dietary lead-in period, patients were randomized to twice-daily placebo or active drug for 16 weeks. Patients receiving 10 mg of pravastatin twice a day for 8 weeks experienced mean total cholesterol and low-density lipoprotein cholesterol (LDL-C) level reductions of 20% (6.85 vs 5.48 mmol/L [265 vs 212 mg/dL]) and 28% (5.17 vs 3.75 mmol/L [200 vs 145 mg/dL]), respectively. At 20 mg twice a day for an additional 8 weeks, pravastatin reduced plasma total cholesterol, LDL-C, and apolipoprotein B-100 levels by 23% (6.85 vs 5.30 mmol/L [265 vs 205 mg/dL]), 31% (5.17 vs 3.59 mmol/L [200 vs 139 mg/dL]), and 23% (118 vs 91 mg/dL), respectively. High-density lipoprotein cholesterol (HDL-C), HDLb-C, HDLb-C, and apolipoprotein A-I plasma concentrations increased by 11%, 60%, 7%, and 10%. Plasma triglyceride concentrations decreased in both the pravastatin- and placebo-treated patients. Pravastatin was generally well tolerated and an effective agent for the treatment of primary hypercholesterolemia.

Mexiletine. Long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.

Amiodarone in the management of refractory atrial fibrillation.

Thirty-eight patients were studied to evaluate amiodarone hydrochloride in the treatment of refractory atrial fibrillation. Among them were 25 with sustained atrial fibrillation and 13 with paroxysmal atrial fibrillation. All patients were symptomatic and refractory to therapeutic doses of at least two conventional drug trials, and patients with atrial fibrillation had relapsed from electroversion. Amiodarone hydrochloride was administered in doses of 5 mg/kg intravenously, then 600 to 800 mg/d for seven to ten days, followed by 200 to 400 mg/d. Holter recordings were obtained every one to three months. The effect of amiodarone on the ventricular rate during sustained atrial fibrillation was evaluated in 18 patients and decreased from 99/min (range, 72/min to 143/min) at baseline to 75/min (range, 60/min to 102/min) at follow-up before conversion. Conversion to normal sinus rhythm occurred in 19 patients (76%), including 11 with and eight without direct-current cardioversion. During long-term treatment, sinus rhythm was sustained on an average of 16 months (range, three to 27 months) in 20 patients (53%). This included 11 of 25 patients with sustained atrial fibrillation and nine of 13 patients with paroxysmal atrial fibrillation, with only four of these patients relapsing. Four patients (11%) developed intolerable side effects, but no serious toxic effects were encountered, perhaps because of the relatively low doses of amiodarone hydrochloride that were used (average, 232 +/- 80 mg/d). Amiodarone is a safe and effective alternative to standard therapy in patients with refractory sustained or paroxysmal atrial fibrillation.

The incidence, magnitude, and time course of the amiodarone-warfarin interaction.

Eight patients concurrently treated with amiodarone and warfarin sodium were studied to characterize the interaction between these drugs. All fulfilled the following criteria: (1) stable and therapeutic prothrombin time (PT) at baseline, defined as at least two consecutive PTs obtained within two weeks before beginning amiodarone therapy that varied by less than or equal to 15%; (2) no warfarin dosage adjustment in the two weeks prior to amiodarone therapy; (3) no other drugs given that alter coagulation study results; and (4) follow-up PTs obtained 1, 2, 4, and 8 weeks after initiation of amiodarone treatment. A clinically significant change in PT was defined as greater than 15%. Mean baseline PT was 19.8 s for patients receiving 5.99 mg/d of warfarin sodium. Patients had a mean maximum increase in PT of 44% (range, 22% to 108%), which occurred during the first two weeks. In six patients, the PT returned to within 15% of baseline by week 4 or 8, and the daily warfarin requirement had decreased by 35% (range, 25% to 50%). Two patients had PTs varying by greater than 15% from baseline at week 8 despite a 33% reduction in warfarin dosage in each case. No patient in this series encountered complications of anticoagulant therapy, perhaps due to early recognition and dosage reduction. Although the mechanism remains unclear, our study indicates that amiodarone potentiation of warfarin effects occurs in all patients, occurs in the first two weeks of amiodarone therapy, variably increases PT by 22% to 108%, and lowers the warfarin requirement by 25% to 50%. We recommend a 25% prophylactic reduction of warfarin dosage and weekly measurements of PT for one month when amiodarone therapy is initiated.

Potential clinical and economic effects of homocyst(e)ine lowering.

BACKGROUND: Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. SUBJECTS AND METHODS: We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. RESULTS: Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. CONCLUSIONS: Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable costs. If homocyst-(e)ine lowering is considered, a screen and treat strategy is likely to be more cost-effective than universal supplementation. Arch Intern Med. 2000;160:3406-3412.

Electron-beam computed tomography in the diagnosis of coronary artery disease: a meta-analysis.

BACKGROUND: Electron-beam computed tomography (EBCT) is a new, noninvasive method of detecting coronary artery calcification that is being increasingly advocated as a diagnostic test for coronary artery disease (CAD). Before its clinical use is justified, however, the overall accuracy of EBCT must be better defined. OBJECTIVE: To estimate the accuracy of EBCT in diagnosing obstructive CAD. DATA SOURCES: English-language studies from January 1, 1979, through February 29, 2000, were retrieved using MEDLINE and Current Contents databases, bibliographies, and expert consultation. STUDY SELECTION: We included a study if it (1) used EBCT as a diagnostic test; (2) reported cases in absolute numbers of true-positive, false-positive, true-negative, and false-negative results; and (3) used coronary angiography as the reference standard for diagnosing obstructive CAD (defined as > or = 50% diameter stenosis). DATA EXTRACTION: Data were extracted from the included articles by 2 independent reviewers. DATA SYNTHESIS: Weighted pooled analysis and summary receiver operating characteristic (ROC) curve analysis were used to determine sensitivity and specificity rates. Results from 9 studies with 1662 subjects were included. Pooled sensitivity for EBCT was 92.3% (95% confidence interval [CI], 90.7%-94.0%) and pooled specificity was 51.2% (95% CI, 47.5%-54.9%). Maximum joint sensitivity and specificity for EBCT from its summary ROC curve was 75%. As the threshold for defining an abnormal test varied, sensitivity and specificity changed. For a threshold that resulted in a sensitivity of 90%, specificity was 54%; when sensitivity was 80%, specificity rose to 71%. CONCLUSION: The performance of EBCT as a diagnostic test for obstructive CAD is reasonable based on sensitivity and specificity rates from its summary ROC curve.

The effect of coadministration of verapamil on the pharmacokinetics and metabolism of quinidine.

We have previously found that verapamil pretreatment significantly inhibits the metabolism of antipyrine. To assess more fully the implications of this observation, we examined the effect of verapamil on the pharmacokinetics and metabolism of quinidine. Pretreatment with verapamil, 80 mg and 120 mg (every 8 hours for 3 days), reduced the oral clearance of quinidine from 17.0 L/hr to 11.6 and 11.3 L/hr, respectively (P less than 0.01). The half-life of quinidine was also significantly prolonged by verapamil. The formation clearance of 3-hydroxyquinidine was reduced by 61.2% and 70.6% after verapamil pretreatment (80 and 120 mg, respectively) (P less than 0.01), whereas the renal clearance of unchanged quinidine was not affected. These results indicate that verapamil impairs the metabolism of quinidine to 3-hydroxyquinidine and reduces the oral clearance of quinidine to a degree that could be of clinical significance given the narrow therapeutic index of this drug.

Validity of skinfold thickness measures of formerly obese adults.

UNLABELLED: To assess the validity of skinfold thickness estimates of body fatness in formerly morbid obese adults, 23 patients (17 women, 6 men) who had completed a protein-sparing modified fast were studied. Mean +/- SD weight loss was 60.7 +/- 20.6 kg for men and 42.6 +/- 11.5 kg for women. Body density and percent body fatness were determined after weight loss according to four commonly used skinfold equations: Pollock (P); Durnin-Rahaman (D-R); Durnin-Womersley (D-W); and, Jackson-Pollock (J-P). The validity of these measurements was assessed by hydrostatic weighing, which revealed a percent body fatness of 20.4 +/- 6.5 for men and 29.8 +/- 8.4 for women. The mean difference and total error (square root of the mean of squared deviations) between skinfold predicted and hydrostatically-determined percent body fatness for each skinfold equation were: P, 2.0 and 4.9; D-R, 4.2 and 6.6; D-W, 7.1 and 8.4; and, J-P, 0.7 and 4.4. With the exception of the latter equation, all significantly overestimated (p less than 0.01) hydrostatically-determined percent body fatness. CONCLUSION: Select skinfold equations may result in a marked overestimation of body fatness in formerly obese patients.

Association between self-reported physical activity and vascular reactivity in postmenopausal women.

Short-term exercise training has been associated with improved endothelial-dependent vasodilation, but the impact of long-term habitual physical activity on vascular reactivity is not established. We studied the correlation between self-reported, habitual physical activity and vasoreactivity in non-smoking, non-diabetic, postmenopausal women (n=34, mean age 65.6+/-7.4 years). Vasoreactivity was evaluated by the percentage and absolute change in brachial artery diameter in response to reactive hyperemia induced by occlusion-release, and in response to cold pressor testing (CPT). Habitual physical activity was assessed by a standardized questionnaire based on participant recall. Our results indicate that 64.7% of the women were exercising-to-sweat > or =1x/week, 4.8 flights of stairs were climbed/day, 5.0 city blocks were walked/day and 29.4% participated in moderately physically demanding daily activity. There was a significant association between the number of city blocks walked daily and exercising-to-sweat > or =1x/week with brachial artery percentage and absolute change to CPT (P<0.05). Women who reported a moderately physically demanding daily activity had a significantly greater brachial reactivity percentage change in response to CPT compared with those performing less demanding daily activity (2.0+/-3.6 versus 1.4+/-7.0%, P<0.05). The response to reactive hyperemia was also greater in those women reporting moderately physically demanding daily activity compared to less active women (6.5+/-5.4 versus 5.8+/-5.9%, P=n.s.), but this did not reach statistical significance. Stepwise, multivariate analysis adjusting for body mass index and HDL-cholesterol eliminated the association between physical activity and brachial reactivity in response to CPT, suggesting that physical activity may affect vasoreactivity via these mechanisms. This study suggests that moderate levels of self-reported physical activity are associated with a greater brachial reactivity in response to CPT and supports the recommendation that moderate intensity physical activity may be cardioprotective in postmenopausal women.

Procainamide-induced lupus erythematosus pericarditis encountered during coronary bypass sugery.

Procainamide is probably the most common offending drug responsible for the drug-induced lupus erythematosus syndrome today. Pericarditis has been reported to occur in from 14 to 18 per cent of the cases of procainamide-induced lupus erythematosus, and occasional reports of massive pericardial effusion, pericardial tamponade and constrictive pericarditis have appeared in the literature. We describe a patient who presented with features of procainamide-induced lupus erythematosus without any clinical evidence of pericarditis. He underwent coronary bypass surgery 12 days after administration of the drug was stopped and was found to have a significant pericardial effusion at the time of surgery; histologic examination of pericardial tissue and pericardial fluid confirmed that the pericardial effusion was related to the procainamide-induced lupus syndrome. The incidence of pericarditis in procainamide-induced lupus erythematosus may be higher than presently accepted figures would indicate. Symptoms and signs related to procainamide-induced lupus pericarditis may cause diagnostic confusion with common postoperative bypass complications; the full implications of this disease entity to the patient undergoing coronary bypass are unknown.

Efficacy and safety of pravastatin in the long-term treatment of elderly patients with hypercholesterolemia.

PURPOSE: Elevated cholesterol levels are a major risk factor for coronary heart disease, which remains a significant problem in patients beyond age 65 years. Because drug therapy for the control of hypercholesterolemia in elderly patients is frequently considered to be indicated, we investigated the efficacy and safety of pravastatin in the treatment of elderly subjects with primary hypercholesterolemia. PATIENTS AND METHODS: In this 96-week, multicenter, double-blind, placebo-controlled study, 142 subjects (95 women, 47 men) 64 to 90 years of age with elevated cholesterol levels despite dietary intervention were randomized to receive pravastatin 20 mg at bedtime or matching placebo (2:1). Dosage could be doubled after 8 weeks, a bile acid-binding resin could be added after 16 weeks, and nicotinic acid or probucol could be added after 32 weeks, as needed, to adequately lower the low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: Significant reductions in the levels of LDL-C (-30.9%), total cholesterol (Total-C; -21.9%), and triglycerides (TG; -16.7%) and significant increases in the levels of high-density lipoprotein cholesterol (HDL-C; 11.3%) were noted in the group receiving pravastatin treatment at 16 weeks (P < or = 0.001 compared with baseline, P < or = 0.01 compared with placebo). The cholesterol-lowering effects of pravastatin were sustained throughout the 96 weeks of the trial. Pravastatin was well tolerated, with an overall incidence of adverse events nearly identical to that of placebo. CONCLUSIONS: In this study, pravastatin was well tolerated and effective in lowering LDL-C, Total-C, and TG and in raising HDL-C during long-term treatment of elderly patients with primary hypercholesterolemia.

Concealed ventricular premature complexes in a population sample.

One hundred fifty patients were analyzed with a random sample of patients whose Holter recordings indicated ventricular premature complexes (VPCs). Thirty-five patients (23%) had more than 30 VPCs/hour. Of these 35 patients, 19 had concealed VPCs. This represents 54% of the patients with more than 30 VPCs/hour and 13% of the total sample of 150 patients with VPCs. The most common type of concealed VPCs was the classic concealed bigeminy (S = 2n - 1), which was found in 10 of 19 patients (52%) whose electrocardiograms and patterns were characteristic of concealed VPCs. This was followed by the "even variant" 2n in 5 patients (26%), concealed trigeminy (S = 3n - 1) in 1 (5%), the 3n - 2 variant in 1 (5%) and the "interpolated variant" of 1 + (2n - 1) in 1 (5%). One patient showed a conversion from 2n - 1 to 2n.