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Q We own a 2018 NeXus Bentley diesel pusher, and I've had numerous issues with it. It has a V-bus multiplex electrical system; 2,000-Watt inverter; 50-amp, 12-volt distribution panel; and [...]

OBJECTIVE--Diabetes is often undiagnosed, resulting in incorrect risk stratification for lipid-lowering therapy. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2005-2010 to determine the [...]

OBJECTIVE--To examine an intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) on 4-year change in fitness and physical activity (PA), and to examine the effect of change [...]

OBJECTIVE--To examine the effect of a lifestyle intervention to produce weight loss and increased physical fitness on use and cost of medications to treat cardiovascular disease (CVD) risk factors in [...]

A double-blind, randomized, placebo-controlled, crossover study tested peak and trough efficacy of immediate-release nisoldipine (20 mg twice daily) added to existent [beta]-andrenergic blocking therapy. Patients were randomized with a history of chronic stable angina, while receiving a stable regimen of a [beta]-blocking agent, with exercise test-induced angina in association with 1 mm horizontal or downsloping ST-segment depression and exercise test reproducibility of [+ or -] 15%. Ambulatory electrocardiographic monitoring (48-hour) was performed at 3 of 5 centers (44 patients). Efficacy was achieved in 53 patients (26 taking immediate-release nisoldipine/placebo in sequence and 27 taking placebo/immediate-release nisoldipine in sequence). Total exercise time increased compared with placebo at peak, but only a trend was seen at trough. Time to 1 mm ST-segment depression at peak and trough and ambulatory electrocardiographic parameters were also improved. Adverse effects were mild. This trial confirms that immediate-release nisoldipine when added to existent [beta]-blocker therapy is an active antianginal and anti-ischemic agent, but that the immediate-release formulation loses its antianginal effect at the end of its dosing interval (9 to 14 hours). This drug is therefore being examined in a new extended-release formulation (Coat-Core). (Am J Cardiol 1994;74:1165-1168)

Compared with placebo, adding betaxolol 20 mg every day to nifedipine (up to 60 mg/day in divided doses) or diltiazem (up to 360 mg/day in divided doses) for a 3-week treatment period in 135 patients with stable angina pectoris significantly (p

The efficacy and safety of extended-release isosorbide mononitrate tablets were evaluated in patients with stable effort angina. In a double-blind study, 313 patients with stable effort-induced angina were randomized to receive placebo or extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the morning, Serial exercise testing was performed using the standard Bruce treadmill protocol on days 1, 7, 14, 28 and 42 immediately before morning drug administration, and 4 and 12 hours after administration. After initial dosing, all groups that received extended-release isosorbide mononitrate had significant (p

Increasing knowledge of the complex mechanisms involved in maintaining normal vascular tone enable selection of targeted antianginal therapies. However, the individual response of each patient will direct the choice of medication used to alleviate ischemic symptoms. Moreover, an appreciation of risk reduction through diet and lipid-lowering efforts becomes more important as the dynamic and intricate roles of the endothelium and endothelium-derived relaxing factor in modulating vasomotor tone become apparent.

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IMPORTANCE: High-intensity statins are recommended following myocardial infarction. However, patients may not continue taking this medication with high adherence. OBJECTIVE: To estimate the proportion of patients filling high-intensity statin prescriptions following myocardial infarction who continue taking this medication with high adherence and to analyze factors associated with continuing a high-intensity statin with high adherence after myocardial infarction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of Medicare patients following hospitalization for myocardial infarction. Medicare beneficiaries aged 66 to 75 years (n = 29 932) and older than 75 years (n = 27 956) hospitalized for myocardial infarction between 2007 and 2012 who filled a high-intensity statin prescription (atorvastatin, 40-80 mg, and rosuvastatin, 20-40 mg) within 30 days of discharge. Beneficiaries had Medicare fee-for-service coverage including pharmacy benefits. EXPOSURES: Sociodemographic, dual Medicare/Medicaid coverage, comorbidities, not filling high-intensity statin prescriptions before their myocardial infarction (ie, new users), and cardiac rehabilitation and outpatient cardiologist visits after discharge. MAIN OUTCOMES AND MEASURES: High adherence to high-intensity statins at 6 months and 2 years after discharge was defined by a proportion of days covered of at least 80%, down-titration was defined by switching to a low/moderate-intensity statin with a proportion of days covered of at least 80%, and low adherence was defined by a proportion of days covered less than 80% for any statin intensity without discontinuation. Discontinuation was defined by not having a statin available to take in the last 60 days of each follow-up period. RESULTS: Approximately half of the beneficiaries were women and fourth-fifths were white. At 6 months and 2 years after discharge among beneficiaries 66 to 75 years of age, 17 633 (58.9%) and 10 308 (41.6%) were taking high-intensity statins with high adherence, 2605 (8.7%) and 3315 (13.4%) down-titrated, 5182 (17.3%) and 4727 (19.1%) had low adherence, and 3705 (12.4%) and 4648 (18.8%) discontinued their statin, respectively. The proportion taking high-intensity statins with high adherence increased between 2007 and 2012. African American patients, Hispanic patients, and new high-intensity statin users were less likely to take high-intensity statins with high adherence, and those with dual Medicare/Medicaid coverage and more cardiologist visits after discharge and who participated in cardiac rehabilitation were more likely to take high-intensity statins with high adherence. Results were similar among beneficiaries older than 75 years of age. CONCLUSIONS AND RELEVANCE: Many patients filling high-intensity statins following a myocardial infarction do not continue taking this medication with high adherence for 2 years postdischarge. Interventions are needed to increase high-intensity statin use and adherence after myocardial infarction.

Dilevalol combines vasodilation due to selective [[beta].sub.2] agonism and nonselective [beta] antagonism. We studied 311 patients randomized to dilevalol and 138 to metoprolol in a multicenter trial. After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure

Using serial M-mode echocardiographic determinations of left ventricular (LV) mass and function, the effects of dilevalol, a selective [[beta].sub.2] agonist with nonselective [beta]-antagonist properties, were compared with those of metoprolol in 2 centers in double-blind, randomized clinical trials using similar protocols in nonelderly hypertensive patients (aged

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Background:Mixed evidence suggests that second-generation antidepressants may increase the risk of cardiovascular and cerebrovascular events. Objective:To assess whether antidepressant use is associated with acute coronary heart disease (CHD), stroke, cardiovascular disease (CVD) death, and all-cause mortality. Methods:Secondary analyses of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) longitudinal cohort study were conducted. Use of selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, bupropion, nefazodone, and trazodone was measured during the baseline (2003-2007) in-home visit. Outcomes of CHD, stroke, CVD death, and all-cause mortality were assessed every 6 months and adjudicated by medical record review. Cox proportional hazards time-to-event analysis followed patients until their first event on or before December 31, 2011, iteratively adjusting for covariates. Results:Among 29 616 participants, 3458 (11.7%) used an antidepressant of interest. Intermediate models adjusting for everything but physical and mental health found an increased risk of acute CHD (hazard ratio [HR] = 1.21; 95% CI = 1.04-1.41), stroke (HR = 1.28; 95% CI = 1.02-1.60), CVD death (HR = 1.29; 95% CI = 1.09-1.53), and all-cause mortality (HR = 1.27; 95% CI = 1.15-1.41) for antidepressant users. Risk estimates trended in this direction for all outcomes in the fully adjusted model but only remained statistically associated with increased risk of all-cause mortality (HR = 1.12; 95% CI = 1.01-1.24). This risk was attenuated in sensitivity analyses censoring follow-up time at 2 years (HR = 1.37; 95% CI = 1.11-1.68). Conclusions:In fully adjusted models, antidepressant use was associated with a small increase in all-cause mortality.

Silent myocardial ischemia is characterized by asymptomatic periods of inadequate blood flow to the heart. There is disagreement about the prevalence (number of cases) of silent myocardial ischemia among different ethnic groups. This condition has rarely been reported among Chinese. There is also disagreement about the use of ambulatory electrocardiographic monitoring to diagnose symptomless ischemia. Twenty-four hour monitoring of 1,285 Chinese people was undertaken. Among the 251 persons who had a history of heart attack, almost half were found to have silent myocardial ischemia. Less than one-quarter of the 706 patients with angina (chest pain caused by myocardial ischemia) showed evidence of silent ischemia. Of the clinically normal subjects, under three percent had electrocardiographic evidence of ischemia. The group of Chinese patients with angina had fewer episodes of silent myocardial ischemia than found in other studies of angina patients; however, the prevalence of silent ischemia among the Chinese who had a prior heart attack was higher. The heart rate at the beginning of ST depression (an indication of ischemia, based on the electrocardiogram) was lower during ambulatory monitoring than during exercise testing. Ischemia during ambulatory monitoring was also less frequent than during exercise testing. While the Chinese patients were awake, silent myocardial ischemia occurred with relatively low work loads. (Consumer Summary produced by Reliance Medical Information, Inc.)

To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy.

Background: A majority of all myocardial infarctions occur in patients who are 65 years of age or older and have average cholesterol levels, but little information is available on whether cholesterol lowering in such patients reduces the rate of recurrent cardiovascular disease. Objective: To determine whether pravastatin reduces the rate of recurrent cardiovascular events in older patients. Design: Subset analysis of a randomized, controlled trial. Setting: 80 hospitals and affiliates in the United States and Canada. Patients: 1283 patients aged 65 to 75 years who had had myocardial infarction and had a plasma total cholesterol level less than 6.2 mmol/L (240 mg/dL) and a low-density lipoprotein cholesterol level of 3.0 to 4.5 mmol/L (115 to 174 mg/dL). Intervention: Pravastatin, 40 mg/d, or placebo. Measurements: Five-year event rates of major coronary events (coronary death, nonfatal myocardial infarction, angioplasty, or bypass surgery) and stroke. Results: Major coronary events occurred in 28.1% of placebo recipients and 19.7% of pravastatin recipients (difference, 9.0 percentage points [95% Cl, 4 to 13 percentage points]; relative risk reduction, 32%; P [is less than] 0.001). Coronary death occurred in 10.3% of the placebo group and in 5.8% of the pravastatin group (difference, 4.6 percentage points [Cl, 1.9 to 6.5 percentage points]; relative risk reduction, 45%; P = 0.004). Stroke incidence was 7.3% in the placebo group and 4.5% in the pravastatin group (absolute reduction, 2.9 percentage points [Cl, 0.3 to 4.5 percentage points]; relative reduction, 40%; P = 0.03). The numbers of older patients needed to treat for 5 years were 11 (Cl, 8 to 24) to prevent a major coronary event and 22 (Cl, 15 to 53) to prevent a coronary death. For every 1000 older patients treated, 225 cardiovascular hospitalizations would be prevented compared with 121 hospitalizations in 1000 younger patients. Conclusions: In older patients with myocardial infarction and cholesterol levels in the average range, pravastatin is associated with a clinically important reduction in risk for major coronary events and stroke. Given the high cardiovascular event rate in older patients, the potential for absolute benefit in this age group is substantial., Pravastatin appears to reduce the risk of heart attacks and stroke in older patients with average levels of blood cholesterol and a previous heart attack. Pravastatin is a cholesterol-lowering drug. Researchers treated 1,283 elderly patients, with average cholesterol levels of 240 mg/dL, with either pravastatin or a placebo. In five years of study, 19.7% of patients taking pravastatin, and 28.1% of patients taking a placebo, had a heart attack or other major coronary event. Pravastatin treatment lowered the risk of heart attack by 45% and the stroke risk by 40% in this group of elderly patients.

To investigate the longitudinal relationships between actigraph-derived sleep duration, fragmentation, and lipid levels.

The purpose of this study was to identify determinants of 20-year change in left ventricular (LV) mass (LVM) and LV geometry in black and white young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND Between the ages 45 and 65 years, incident stroke is 2 to 3 times more common in blacks than in whites, a difference not explained by traditional stroke risk factors. METHODS Stroke risk was assessed in 27 748 black and white participants recruited between 2003 and 2007, who were followed up through 2011, in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Racial differences in the impact of systolic blood pressure (SBP) was assessed using proportional hazards models. Racial differences in stroke risk were assessed in strata defined by age (<65 years, 65-74 years, and ≥75 years) and SBP (<120 mm Hg, 120-139 mm Hg, and 140-159 mm Hg). RESULTS Over 4.5 years of follow-up, 715 incident strokes occurred. A 10–mm Hg difference in SBP was associated with an 8% (95% CI, 0%-16%) increase in stroke risk for whites, but a 24% (95% CI, 14%-35%) increase for blacks (P value for interaction, .02). For participants aged 45 to 64 years (where disparities are greatest), the black to white hazard ratio was 0.87 (95% CI, 0.48-1.57) for normotensive participants, 1.38 (95% CI, 0.94-2.02) for those with prehypertension, and 2.38 (95% CI, 1.19-4.72) for those with stage 1 hypertension. CONCLUSIONS These findings suggest racial differences in the impact of elevated blood pressure on stroke risk. When these racial differences are coupled with the previously documented higher prevalence of hypertension and poorer control of hypertension in blacks, they may account for much of the racial disparity in stroke risk.

In this review, we discuss the possible pathophysiological mechanisms and the role of arterial stiffness as a biomarker, a blood pressure–independent predictor of cardiovascular morbidity and mortality. The effects of different antihypertensive drug classes on noninvasively assessed markers of arterial stiffness are also discussed. Current evidence will be reviewed regarding the effect of drugs on arterial stiffness, including the peripheral and central effects of angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, dihydropyridine calcium channel blockers, beta blockers (including vasodilating beta blockers), diuretics, and mineralocorticoid antagonists.

Background: The introduction of chronotherapy (that is improving a drugs therapeutic efficacy by paralleling the drugs plasma levels to circadian rhythms) has recently become a focus of interest. Objective: This article addresses the efficacy and potential shortcomings of chronotherapy, and focuses on one specific type of chronotherapy: a novel long-acting diltiazem formulation, DTZ-LA. Methods: We reviewed the literature to assess the clinical benefits and shortcomings associated with DTZ-LA in the management of hypertension and angina. Results/conclusions: The clinical benefits of DTZ-LA outweigh its disadvantages when surrogate outcomes are evaluated, but it still remains to be determined whether chronotherapy benefits hard clinical outcomes. Nonetheless, chronotherapy has the potential to address the cardiovascular triggers that peak in the early morning hours when the preponderance of cardiovascular events occur, as well as providing better target organ protection compared with non-chronotherapeutic therapy.

Adult survivors of childhood acute lymphoblastic leukemia (ALL) have an earlier than expected mortality from cardiovascular disease. This study examined endothelial function in 75 young (age 30.2±7.1 y) adult survivors of childhood ALL who received chemotherapy without cranial radiation (n25) or chemotherapy combined with cranial radiation (n50) compared with a healthy control group of similar sex, age, and weight (n59).

Randomized controlled trials remain the gold standard study design and yield the highest level of scientific credence. However, recognition of the limitations of the randomized controlled trial is important. This review highlights 10 potentially problematic areas one should carefully assess when performing or reading an article reporting the results of a randomized controlled trial, problematic areas that can affect the outcome of the trial and therefore mislead the reader. These areas include ethical issues, eligibility criteria, masking (blinding), randomization, analytic methods, the selection of subjects for the interventional and comparison groups, selection of end points, and the interpretation of the results. Each of these is discussed, and examples of published articles are used to highlight the main points.

Legal statutes and scientific research have been essential to the Forest Service mission for the past 100 years. Congressional direction for administration of the forest reserves, now called national forests, began in 1897 with passage of the Organic Administration Act. One of the defined purposes for which federal forest lands were set aside from settlement was “securing favorable conditions of water flow.” Since then, more than 25 other federal statutes have further defined watershed management on these lands. The Research branch began watershed experiments in 1910 and did most of the watershed work by the Forest Service until the 1970s. Contributions of key individuals, the Civilian Conservation Corps, the barometer watershed program of the 1960s, and other programs in the National Forest System and the State and Private Forestry branches are examined.

Hypertension is associated with increased cardio- and cerebrovascular morbidity and mortality; antihypertensive drugs have been shown to reduce the risk of adverse cardio- and cerebrovascular events. These events tend to be more common during the morning hours, a time when both normo- and hypertensives show a circadian peak in blood pressure (BP). Although clinicians have a number of safe and well-tolerated antihypertensive agents in various classes and formulations at their disposal, few are designed to specifically attenuate the morning BP surge while maintaining 24-h efficacy. A novel, once-daily, long-acting formulation of diltiazem HCl (DTZ-LA) has been developed with chronodynamics in harmony with diurnal BP variation. DTZ-LA effectively reduces BP in a dose-dependent fashion over a 24-h dosing interval in patients with moderate-to-severe essential hypertension. When compared with a morning dose, the evening dose is associated with significant and clinically meaningful greater reductions in BP during the morning hours, when adverse cardiovascular events tend to cluster. Evening-dosed DTZ-LA was more effective than morning-dosed amlodipine in reducing morning diastolic BP in African-Americans. Evening-dosed DTZ-LA was also more effective than evening-dosed ramipril in reducing morning BP. Evening dosing of DTZ-LA significantly increased exercise tolerance in patients with angina pectoris over the 24-h interval. DTZ-LA is associated with adverse effects consistent with other diltiazem formulations, and overall is safe and well tolerated, even when titrated to doses of 540 mg/day.

Drugs and diseases have differential effects on functional and structural components of large‐conduit arteries and smaller vessels. The objective of this study was to demonstrate functional and structural effects of doxazosin (DOX) on large‐ vessel and small‐vessel arterial elasticity in hypertension (HTN). This was an open‐label, single‐blind, active‐therapy study. Patients with stage 1to 2 HTN were administered DOX 2 mg/day for 3 months and 4 mg/day for 1 month, if indicated, followed by 2‐week washout period. Arterial elasticity was measured noninvasively at baseline, at 3 months and 4 months of treatment, and 2 weeks following DOX withdrawal. Although the observed effects were not statistically significant, large‐vessel elasticity (C1) increased in a dose‐related manner and returned to baseline 2 weeks after drug withdrawal. There was a trend toward an increase in small‐vessel elasticity in a dose‐related manner. However, 2 weeks after drug withdrawal, C2 (distal elasticity) had not returned to baseline and was statistically significantly different from baseline (p = 0.032). It was concluded that large‐artery compliance increased in a dose‐related manner. Almost all benefit was lost within 2 weeks of discontinuation, suggesting the DOX effect was functional. Small‐artery compliance improved in a dose‐related manner but only partially returned to baseline after DOX withdrawal, suggesting changes in artery structure by DOX.

Two cases of chloral hydrate overdosage were associated with multiform ventricular tachycardia. Both were refractory to a number of antiarrhythmics, but responded to propranolol administration. Two of nine other cases reported in the literature also responded to beta-blocking agents. Mechanisms for the arrhythmia and its apparent response to beta blockade are discussed.

L‐ and T‐type voltage‐dependent transmembrane calcium channels are important for normal functioning of the cardiovascular system. T‐type channels are a heterogeneous group, and have physiologic and pathophysiologic relevance in a number of organ systems, including the heart and central nervous system. They appear to be involved in the control of blood pressure in patients with essential hypertension and in protection from ischemic damage. Alterations of both L‐ and T‐type calcium channels are involved in the development of hypertension. Pharmacologic modulation of T‐type calcium channels appears to reduce membrane calcium flux and ameliorate hypertension. During early ischemic damage, T‐type calcium channels appear to remain functional whereas L‐type channels are already inactivated. T‐type calcium channels also appear to be involved in the development of supraventricular arrhythmias, some forms of arrhythmias in cardiomyopathy, and cardiac hypertrophy. The heterogeneity of T‐type calcium channels should make it possible to target drugs to specific subgroups of T‐type calcium channels. A new class of calcium antagonist, the benzimidazolyl‐substituted tetraline derivatives, has been shown to block both L‐ and T‐type calcium channels. The first member of this class approved for clinical use is mibefradil. Clinical studies have demonstrated the efficacy of mibefradil in lowering blood pressure and as an antianginal and antiischemic agent. At clinically recommended doses, mibefradil has a heart rate lowering effect without a negative inotropic effect, and a favorable side effect profile. Because it is metabolized by the cytochrome P450 pathway, it should be used cautiously with other agents similarly metabolized.

The effectiveness of an intermittent regimen of transdermal nitroglycerin in chronic stable angina was evaluated in 206 patients using serial treadmill testing. After a placebo stabilization phase, patients were randomized to 4 weeks of double-blind treatment with transdermal nitroglycerin, 10 or 20 cm2(equivalent to 5 or 10 mg/24 h) (Group A); transdermal nitroglycerin, 30 or 40 cm2(equivalent to 15 or 20 mg/24 h) (Group B), or placebo. Patches were applied at 8:00 AM and removed at 8:00 PM each day throughout the study. Treadmill testing was performed 0, 4, 8 and 12 h after patch application at baseline (day 0) and on days 1, 15 and 29.

Treatment for patients with cardiovascular disease is discussed.

Fantofarone is a calcium channel antagonist of a class (sulfone indolizine) that is structurally different from the existing classes. The primary cardiac action of fantofarone is on the sinus node, although it is also a potent peripheral and coronary vasodilator. This is a multicenter, double‐blind, randomized, placebo‐controlled, dose‐ranging study evaluating the efficacy and safety of fantofarone. Three hundred and thirty patients were included as intent‐to‐treat, and 299 patients completed the entire protocol. Doses of fantofarone studied were 50, 100, 150, and 200 mg twice daily. The 100‐ and 150‐mg groups demonstrated antianginal activity, prolonging exercise time walking on a treadmill by 38 and 45 seconds to the endpoint of moderate angina, compared with the placebo group. Sinus bradycardia occurred in 23 patients and was somewhat dose‐related. Systolic blood pressure at rest and while exercising was not altered by therapy. No deaths occurred in the treated group. Of the 20 patients in the treatment group who did not complete the protocol (compared with 23 in the placebo group) 6 were dropped because of symptomatic bradycardia, 5 because of increased angina, and 9 for miscellaneous reasons. In doses of 100 mg to 150 mg twice daily, monotherapy fantofarone was effective and safe in the treatment of patients with chronic, stable angina pectoris.

Benazepril hydrochloride (CGS 14824A) is an orally active, nonsulfhydryl compound that is transformed in vivo to a long‐acting inhibitor of angiotensin‐converting enzyme (ACE). Previous studies have shown benazepril to lower blood pressure in hypertensive patients and to confer acute hemodynamic benefits in patients with congestive heart failure (CHF). In the current multicenter investigation, 16 patients with chronic CHF due to left ventricular systolic dysfunction (ejection fraction < 0.40 at rest) whose symptoms corresponded to New York Heart Association classes II to IV were given open‐label benazepril once daily in ascending doses of 2 to 20 mg and followed biweekly for 12 weeks. Evaluation of the 15 subjects who completed the trial showed a progressive increase in treadmill exercise duration (from 7.65 ± 3.64[SD] minutes at baseline to 9.74 ± 3.66 minutes at 12 weeks, P < .001); augmentation of the mean left ventricular ejection fraction (from 0.266 ± 0.133 at baseline to 0.292 ± 0.136 at 12 weeks, P < .025); relief of exertional dyspnea in 7 of the 15 patients(P < .02); and improvement in global symptomatic status in 10 of the patients(P < .01). These responses were accompanied by a reduction in serum ACE activity of 75% (from 27.2 ± 10.5 IU/L at baseline to 6.7 ± 1.9 IU/L at 12 weeks, P < .001), which was independent of dose and duration of treatment. The magnitude of ACE inhibition did not correlate with changes in the efficacy variables. Aside from two instances of symptomatic hypotension (one of which was complicated by volume depletion), the drug was well tolerated. Long‐term therapy with benazepril for patients with CHF shows promise. A large‐scale, double‐blind trial of benazepril in this population is currently in progress.

This is the first reported large clinical trial of the antianginal and acute ischemic effectiveness and safety of dilevalol (the R, R‐isomer of labetalol) in patients with chronic stable angina pectoris. This was a multicenter double blind fixed‐dose parallel group placebo controlled trial. Patients with chronic stable angina and positive and reproducible exercise tests (±20%) were included. If randomized, patients entered one of four fixed dose groups (twice a day placebo, 100 mgm, 200 mgm and 400 mgm bid for 2 weeks). Exercise testing was performed at 2 hours (peak) and 12 hours (trough) postdosing. This was followed by a 2‐week once‐a‐day dosing regimen in which patients received the same total daily dose as the prior 2 weeks, with the full dose in the morning and a matched placebo in the evening. Exercise testing was performed at 2 hours (peak) and 24 hours (trough) postdosing. Anginal frequency and NTG consumption were significantly reduced, and equally so, by qd and bid regimens. The time of exercise to the onset of angina increased and the proportion of patients terminating exercise because of moderate angina decreased in a dose response fashion for both peak and trough tests and for both qd and bid regimens. There was also a dose related decrease in exercise induced ST segment depression and an increase in time to 1 mm ST depression. In 15 patients, 24‐hour ambulatory monitoring also revealed a decrease in episodes of silent ischemia. No significant side effects related to the study drug occurred. Thus, dilevalol was effective in the treatment of angina pectoris since it was well tolerated, favorably improved exercise induced ischemia (both painful and silent ischemia), and reduced anginal frequency and NTG consumption.

Arterial compliance, defined as a change in dimension in response to a given change in stress, is becoming an increasingly important clinical parameter. Related concepts, such as distensibility, elasticity, and stiffness, and more traditional concepts such as resistance, afterload, and impedance need to be differentiated from compliance, although they are frequently (inappropriately) used interchangably. Many studies cannot differentiate between compliance changes due to a drug's effect on blood pressure and those due to a drug's effect on vessel wall integrity. This differentiation is important because a more physiologic therapy, one that benefits pulsatile and nonpulsatile flow, should be of greater clinical benefit than a therapy that only lowers blood pressure. A number of methods have been used to estimate compliance, but to date there is no generally agreed‐on best method. There also are no longitudinal studies that relate abnormal compliance and drug effects to outcome. Nonetheless, patients at risk from a variety of disease states, such as hypertension, diabetes mellitus, and hypercholesterolemia, may benefit from earlier recognition of abnormal compliance. Earlier recognition may lead to interventions that would reduce their risk. This review includes a discussion of compliance and related estimates of blood vessel function and attempts to summarize the data currently available regarding the effects of cardioactive drugs on arterial compliance.

A double‐blind, randomized, placebo‐controlled study was conducted to test the peak and trough antianginal and antiischemic monotherapy efficacy and safety of a new extended‐release formulation of nisoldipine (nisoldipine Coat Core [Bayer Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study patients had a history of chronic, stable angina pectoris, exercise‐induced angina in association with ST segment depression, and exercise test reproducibility. Of the 483 patients enrolled in the study, results were valid for safety analysis for 312 and for efficacy analysis for 284. There was a statistically significant improvement in total exercise time at both peak and trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients taking placebo, but the group taking 60 mg was not better than the group taking 20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar for the secondary endpoints (time to onset of angina and time to 1 mm ST segment depression). No correlation was evident between plasma nisoldipine levels and total exercise duration. Headache and peripheral edema were the most frequently reported adverse events and were dose related. There were no discontinuations due to adverse events in patients randomized to the 20‐mg nisoldipine group. No deaths occurred while patients were receiving active nisoldipine therapy. Therapy with this extended‐release formulation of nisoldipine is an effective once‐daily treatment for chronic stable angina pectoris. It represents one of the few dihydropyridine calcium channel antagonists that has shown efficacy when administered as monotherapy to patients with angina.

Objectives. We sought to determine the effect of pravastatin on recurrent cardiovascular events in women with average cholesterol levels after myocardial infarction (MI).

Objectives. We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms.

The correction of shunts resulting from partial anomalous pulmonary venous drainage has become an accepted surgical procedure. Surgical complications, other than those that were purely postoperative, have been rare. The present report details the case histories of three patients with unusual complications resulting from this type of surgery. Unilateral pulmonary venous obstruction and repeated infections occurred in one patient. In another, obstruction of the superior vena cava resulted. In the third patient, an inadequate operation was performed when the site of partial anomalous pulmonary venous drainage into the coronary sinus was not recognized initially at the time of surgery.

The correlation of symptoms (SX) with major arrhythmias (ARS) occurring during 24-hour ambulatory monitoring (AM) was investigated in a group of patients referred because of dizziness or syncope. Ninety-eight consecutive patients, ages 25 to 82, who had adequate diaries of activities and SX, were included. The ARS considered to be major were ventricular and supraventricular ectopy grade 2, 3, and 4 (Lown classification), sinus arrest and block, atrioventricular block, and sinus bradycardia ≤ 40/minute. Although all patients were referred because of dizziness and/or syncope, only 41 (42 percent) had their symptoms during the recording period. The ARS were recorded in 63 (64 percent). There was no statistically significant difference in the incidence or in the type of ARS in the group with, and the group without, symptoms (χ2= 1.64). Of the 23 subjects with both major ARS and recorded SX, only two had SX and ARS occurring concomitantly. It is concluded that (1) this is a group with a high prevalence of major ARS, (2) there was correlation between major ARS recorded and SX reported in a very small percent of cases (2 percent), (3) treating the ARS in the others could not be expected to abolish the SX, and (4) the high cost of monitoring should be considered in this context

This study was designed to evaluate the effects of a new beta‐adrenergic blocking agent with beta2agonist activity (dilevalol, an R‐R' isomer of labetalol) on left ventricular hypertrophy regression as seen by M‐mode echocardiography. The study design was a 2:1 double blind randomization of dilevalol versus metoprolol. There was an equal blood pressure reduction in the two groups (supine diastolic blood pressure fell from 101 ± 4.5 mm Hg to 87 ± 13.7 mm Hg, P < .001 in the dilevalol group, and 101 ± 4.3 mm Hg to 87 ± 8.6 mm Hg, P < .01, in the metoprolol group). At the end of 2 months, there was an overall 7.5% decrease in left ventricular mass index in the 16 dilevalol treated patients (this was due to a 4.4% decrease in posterior wall thickness, end diastolic dimension increased by only 1%). Of the seven patients with an increased left ventricular mass index, all demonstrated hypertrophy regression (mean 17.14%). In contrast, no significant change in left ventricular mass was seen in the metoprolol treated group. Echocardiography left ventricular mass index and electrocardiographic evidence of left ventricular hypertrophy (using the Sokolow‐Lyons criteria and Romhilt‐Estes point score) had poor correlation (r = .30 and r = .38, respectively). Resting ejection fraction increased by 5% and velocity of circumferential fiber shortening by 14% in the dilevalol treatment group (not significant), in conclusion, 1) echocardiographic left ventricular hypertrophy regression occurred with dilevalol treatment 2) this left ventricular regression was a result of a decrease in intraventricular septal thickness and posterior wall thickness 3) the poor correlation between echocardiographic increased left ventricular mass and electrocardiographic left ventricular hypertrophy was supported 4) dilevalol and metoprolol had equal antihypertensive effects.

This study addresses the effect of the three major classes of antianginal agents on asymptomatic myocardial ischemia in patients with chronic stable angina pectoris. The authors found that each class (given as monotherapy) resulted in a 50% reduction in asymptomatic ischemia (both in the number of episodes and the ST product). Dual therapy resulted in an overall four fold reduction compared to placebo. Therapy also resulted in a beneficial alteration in the frequency distribution of asymptomatic ischemia. Stratification into three age groups demonstrated an equal prevalence of asymptomatic ischemia in each. All ages had nearly equivalent reductions in asymptomatic ischemia by monotherapy and dual therapy, but the youngest age group seemingly responded better to monotherapy than did the oldest age group.

Study Objective. To determine the safety and efficacy of diltiazem CD 180 mg administered once/day in patients with chronic stable angina inadequately controlled with β‐blockers, long‐acting nitrates, or both.

In order to delineate the frequency of arrhythmias and conduction abnormalities in a group of apparently healthy elderly people, 24-hour ambulatory ECG recordings were obtained on subjects recruited from the Veterans Administration Voluntary Service. Their ages ranged from 60–84 (average 69). It is concluded from this preliminary study that complex supraventricular and ventricular arrhythmias occur in an apparently healthy elderly population. These findings must be taken into account in assessing the clinical significance of arrhythmias in an elderly population.

Recognized electrocardiographic abnormalities associated with pericardial disease include ventricular repolarization phenomena and simultaneous electrical alternans of the P wave and QRS complex. Atrial ST segment changes (S-Ta segment) have also been described in pericardial disease but not recently emphasized. Five patients had S-Ta segment changes (two with uremic pericarditis, two with hemorrhagic pericarditis caused by ruptured aneurysms, and one with idiopathic pericarditis). Four patients had S-Ta segment change resolution concomitant with clinical improvement; the remaining patient died prior to pericarditis resolution. The electrocardiographic findings in each case demonstrated elevation of S-Ta segments in aVR and depressions in other leads in addition to ventricular repolarization abnormalities. Atrial injury currents occur in pericarditis in the absence of other known causes of atrial injury. The incidence of this electrocardiographic finding in pericarditis is unknown but is apparently common.

Transvenous cardiac pacing is now routinely used as therapy for heart block. As experience with transvenous pacing has increased, it has become apparent that a significant cause of pacemaker failure has resulted from malposition of the electrode catheter in the coronary veins. A simple technique ensures proper placement of the electrode catheter in the right ventricle by utilizing the intracavitary electrocardiogram.