One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.

Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.

OBJECTIVES: To clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage. BACKGROUND: LV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated. DESIGN: Cross-sectional case-control study. SETTING: Baseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group. PATIENTS/PARTICIPANTS: Nine hundred and sixty-four patients with Stage I-II hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) x QRS > 2440 mm x ms) or modified Sokolow- Lyon voltage criteria (SV1 + RV5/RV6 > 38 mm), and 366 apparently normal adults. INTERVENTIONS: None. METHODS: Two-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test RESULTS: Mean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/ beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (Multiple R + 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (all P< 0.001). Relative wall thickness was independently related (Multiple R + 0.50) to older age, higher systolic pressure, lower SV (all P< 0.001) and higher body mass index (P + 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening. CONCLUSION: In patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/ SV, are associated with, and may be stimuli to different LV geometric phenotypes.

Optimal antihypertensive therapy for prevention and treatment of left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) is considered an adaptation to a pressure load on the left ventricle and is common in hypertensive patients. The condition is a profound risk factor for cardiovascular events, greater than and independent of blood pressure. It is now recognized in hypertension management guidelines as an indication for more stringent blood pressure control. All of the first-line antihypertensive agents have been shown to variably regress LVH, but no definitive evidence yet shows that one agent is superior to others in decreasing risk independent of blood pressure control. Although some evidence suggests that reduction of LVH is associated with improved prognosis independent of blood pressure control, relative efficacy of drug classes in this regard has yet to be demonstrated. At present, recommendations for optimal therapy in hypertensive patients with LVH must rest on the presence of underlying cardiac and noncardiac conditions, with the understanding that the major classes of antihypertensive agents will probably decrease LVH.

Prevention of coronary heart disease. Part II. Secondary prevention, detection of subclinical disease, and emerging risk factors.

The prevention of CHD should be a major priority among primary care physicians and subspecialists who have any dealing with the cardiovascular system. There is ample evidence from epidemiologic studies for the impact of specific risk factors on CHD events. There is also ample evidence from observational studies and clinical trials that interventions of lifestyle and pharmacologic therapy can decrease morbidity and mortality from CHD before or after the first event. It behooves the physician who wishes to practice good medicine to understand the pathophysiologic roles of the risk factors and the evidence from epidemiologic studies and clinical trials for their association with cardiovascular disease. It is important to determine the efficacy of interventions, both lifestyle and pharmacologic, in modifying CHD risk. To be effective in doing so, the practicing physician has to have the motivation to determine target goals for risk factor modification in each patient, to understand the patient's own motivations in modifying risk factors, and to define clearly with the patient the expectations of such interventions. Although there are guidelines for risk factor modification in modification of cholesterol and in hypertension, the periodic renewal of these guidelines reflects the changing concepts of risk and its modification. A cardiovascular risk factor intervention categorization is presented in Table 12. The physician must be convinced that such intervention is beneficial to the patient, cost-effective, and thus fulfills the expectations of medical practice. The practice of medicine in the evaluation and treatment of coronary heart disease has always been challenging and stimulating. The prevention of CAD disease should ultimately provide the greatest accomplishment.

Impact of different partition values on prevalences of left ventricular hypertrophy and concentric geometry in a large hypertensive population : the LIFE study.

Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m(2)) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height(2.7) (g/m(2.7)) PV 51/51 or 49.2/46.7. RWT was calculated by either 2xend-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2xPWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height(2.7) PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height(2.7) identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications?

OBJECTIVES: The goal of this review is to reevaluate the unstable coronary syndromes in the setting of new therapies and biochemical markers. BACKGROUND: Patients with acute coronary syndromes comprise a large subset of many cardiology practices. Patients with unstable angina (UA) and non-Q wave myocardial infarction (NQMI) may sustain a small amount of myocardial loss but have significant amounts of viable, yet ischemic, myocardium, placing them at high risk for future cardiac events. In the past, enzyme differentiation of NQMI from UA was considered important to assess prognosis and direct therapy. METHODS: Manuscripts published in peer-reviewed journals over the past three decades were reviewed and selected for this review. Recent abstracts were also considered and cited where appropriate. RESULTS: In the late 1990's, although UA and NQMI remain parts of a spectrum, it is apparent that the distinction between these two entities is no longer sufficient to identify high risk patients; rather, specific electrocardiographic changes, aspects of the clinical history, newer biochemical markers, and angiographic findings help to better distinguish higher risk individuals from a large patient population with unstable coronary syndromes and these factors usually determine therapy. CONCLUSIONS: Based on these results, it is likely that newer therapies such as glycoprotein IIb/IIIa receptor antagonists, low molecular weight heparins, and coronary stents will be directed toward these high risk patients.

Prevention of coronary heart disease. Part I. Primary prevention.

The first concern in primary prevention is the physician's belief that primary prevention is important for all adults and that intervention can significantly affect risk. Given the coronary plaque burden over many years and the importance of the development of healthy lifestyles early in adulthood to decrease coronary plaque burden, there are excellent reasons to begin prevention even with young adults. At the very least, a patient seen for any reason should provide a smoking history, have knowledge of the presence of early CHD in first-degree relatives and measurements of blood pressure, height, and weight, provide evidence for a cholesterol level within 5 years (after age 20 according to NCEP guidelines or in middle age according to ACP guidelines), and be given an assessment of glucose tolerance or diabetes. Information about alcohol intake and physical activity status are also of some importance. Other than height, weight, and blood pressure, during the physical examination, the physician should initially assess the strength of pulses in the lower extremities, evidence for carotid or femoral bruits, and eyegrounds for retinal arterial changes, and the skin and subcutaneous tissue should be examined for xanthomas and the eyes should be examined for corneal arcus and xanthelesma. These elements should be part of any initial examination by a primary care physician and are not extraordinary. In addition to lipid and blood sugar analyses, other evaluations may include blood urea nitrogen and creatinine and electrolytes in patients with hypertension or diabetes or in patients who are on antihypertensive agents. It may be prudent to obtain an ECG for patients who are older than 40 years. The elements mentioned above are the elements of the history, physical examination, and laboratory examination in subjects without a past history of CHD and with no clinical evidence for CHD. Primary prevention management begins with a discussion of risk factors with the patient. The key interventions aim at the lowering of blood pressure to at least less than 140/90 mm Hg, the complete cessation of smoking, the lowering of lipid levels to less than 130 mg/dL, the lowering of triglycerides to less than 200 mg/dL (or, some would argue, < 150 mg/dL), and the attempt to keep HDL cholesterol above 35 mg/dL (more than 40 to 45 mg/dL is a better goal) with the use of lifestyle modification. For patients with diabetes, strict control of glucose levels is essential to minimize disease of the microvasculature and possibly to minimize progressive renal disease. There are several lifestyle modifications for lipids. For patients with elevated LDL cholesterol, modifications include a less than 30% fat calorie diet and less than 300 mg of cholesterol intake daily, with fat calories approximately equally distributed among saturated fats, polyunsaturated fats, and monounsaturated fats (1/3, 1/3, 1/3; rule of 3s). The assistance of a dietician is extremely helpful in this regard. For patients with a low HDL cholesterol, weight reduction (for overweight patients) by calorie control and increased physical activity and smoking cessation will have some modest effect. For patients with elevated triglycerides, a diet similar to that for lowering of LDL cholesterol with the addition of stricter calorie limitation, avoidance of refined sugars, increase in complex carbohydrates, and avoidance of alcohol will be helpful. A decrease in the percent of fat calories to 20% to 25% will be of assistance to those patients with particularly high triglycerides. The treatment of underlying conditions such as diabetes mellitus, hypothyroidism, liver disease, and some renal conditions may also significantly modify high triglycerides. For patients with hypertension, limitation of sodium to 2 gm/d (6 gm sodium chloride), limitation of alcohol to 1 to 2 drinks a day, increased physical activity, and weight reduction are the key lifestyle modifications. (ABSTRACT TRUNCATED)

Comparison of cine magnetic resonance imaging and Doppler echocardiography for evaluation of left ventricular diastolic function.

Cine magnetic resonance (MR) imaging of the heart detected evidence of left ventricular (LV) diastolic filling abnormality in patients with LV wall thickening but normal systolic function and normal diastolic function by routine Doppler echocardiography. Cine MR imaging may be more sensitive than routine echocardiography in detecting abnormalities of LV diastolic function.

Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study.

OBJECTIVES: To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. METHODS: The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebo-controlled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n = 132); (2) amlodipine maleate (n = 131); (3) chlorthalidone (n = 126); (4) doxazosin mesylate (n = 134); (5) enalapril maleate (n = 135); or placebo (n = 234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. RESULTS: At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. CONCLUSIONS: In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthali-done and the cardioselective beta-blocker acebutolol appear to improve QL the most. Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general well-being of the individual.

The non-Q wave myocardial infarction revisited: 10 years later.

In the 10 years since our previous review of this topic, the acute coronary syndromes (Q wave myocardial infarction [QMI], non-Q wave MI [NQMI], and unstable angina) have been more clearly categorized. Many of the differences delineated between QMI and NQMI still hold: a less extensive infarction and a lower in-hospital mortality, but a larger degree of jeopardized myocardium leading to a higher incidence of reinfarction and recurrent angina. The pathophysiology of NQMI appears to be similar to that of unstable angina except for the greater incidence and extent of thrombus formation and coronary artery occlusion with NQMI. Prognostic studies have shown that ST depression and anterior infarct location are associated with a greater risk for posthospital clinical events than the findings of ST elevation and other infarct locations. Symptom-limited stress testing using electrocardiogram and thallium-201 imaging are now recommended before discharge or in the early postdischarge period, with coronary arteriography recommended for evidence of residual ischemia. Aspirin and low dose heparin should be administered on admission after NQMI to decrease further thrombus formation, and aspirin continued in the posthospital period. Diltiazem administration is recommended in NQMI without evidence of pulmonary congestion to prevent recurrent nonfatal acute myocardial infarction. Percutaneous transluminal coronary angioplasty and surgical revascularization should be reserved for patients with NQMI with residual ischemia.

Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS)

Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.

Chronobiology of acute myocardial infarction: cardiac arrhythmia suppression trial (CAST) experience.

The onset of acute myocardial infarction (AMI) has been shown to occur in a reproducible pattern with a peak in mid-morning and a secondary peak in late afternoon and early evening. More detailed information on the timing of this catastrophic event may provide important pathophysiologic information. Using the database from the Holter Registry of the Cardiac Arrhythmia Suppression Trial (CAST) (n = 22,516), the day of the week, the month, and season of the onset of AMI was obtained and correlated with demographic characteristics. The pattern of the day of onset for the entire population was significantly nonuniform (p <0.0001) with a Monday peak and a weekend nadir. This pattern was observed in most of the examined subgroups. Analysis of seasonal data revealed nonuniform distribution (p <0.001) with a peak in winter and autumn. We conclude that AMI is not a random event but occurs in definite patterns related to the day of the week and the season of the year. These patterns were observed in a wide variety of patient subgroups and appear related to climate, occupation, and other factors.

Relation of circadian ventricular ectopic activity to cardiac mortality. CAST Investigators.

The relation between the circadian occurrence of ventricular premature depolarizations (VPD) and sudden arrhythmic death was examined in a subset of patients entered into the Cardiac Arrhythmia Suppression Trial (CAST). Ambulatory electrocardiographic recordings with hourly measurement of VPD frequency were available in 357 patients. Forty percent of the patients (142 of 357) demonstrated circadian variation in VPD frequency between 6:00 A.M. and 9:59 A.M. that was significantly higher (p < 0.05) than what could randomly be expected from an overall 24-hour average for that patient. The only baseline characteristics in patients with circadian VPDs were age (p < 0.04), history of cardiac arrest (p < 0.01), presence of higher frequency of VPDs (p < 0.002), more frequent episodes of ventricular tachycardia (p < 0.04), and more frequent episodes of slow runs (p < 0.04). There was no difference in mortality in patients with or without circadian VPD variation; drug treatment did not effect mortality. These data indicate that the presence of circadian VPDs is not a predictor of sudden arrhythmic death in patients with a high frequency of VPDs.

Effect of left atrial size on recurrence of atrial fibrillation after electrical cardioversion: atrial dimension versus volume.

UNLABELLED: There are conflicting reports on the relationship between left atrial dimension (LAD) determined by echo-cardiography and the incidence of atrial fibrillation (AF) recurrence after electrical cardioversion (EC). We hypothesized that left atrial volume (LAV) by echocardiography might better differentiate patients who will have recurrence of AF after EC. METHODS: Forty-one patients having EC for AF were prospectively studied by echocardiography. LAD was measured by American Society of Echocardiography guidelines as the anterior-posterior dimension in the parasternal view. LAV was measured by Simpson's method using an off-line analysis system and reported as the average of values from the apical four-chamber and two-chamber views. RESULTS: (Data are mean +/- SEM): Patient follow-up was 15 +/- 10 months. No cutoff value of LAV predicted AF recurrence, but all three patients with LAD greater than 65 mm had AF recurrence. Compared with patients maintaining normal sinus rhythm (NSR) (N = 18), the AF group (N = 23) had a lower percentage of antiarrhythmic drug use, especially type IA agents (p < .02). Patients who stayed in NSR tended to have shorter AF duration before EC (16 +/- 15 v 63 +/- 122 weeks, p = .08) but did not differ in age (53 +/- 27 v 58 +/- 23 years), LAD (51.1 +/- 7.7 v 54.2 +/- 9.4 mm) or LAV (85.1 +/- 24.3 v 95.1 +/- 33.3 mL). CONCLUSIONS: (1) LAV by echocardiography does not improve identification of patients at risk for recurrence of AF after EC, (2) patients with LAD up to 65 mm may maintain NSR after EC, (3) LAD greater than 65 mm is associated with AF recurrence, and (4) use of antiarrhythmic drugs and the duration of AF before EC may be better predictors of maintenance of NSR than echocardiographic measures of left atrial parameters.

Alpha-blockade and thiazide treatment of hypertension. A double-blind randomized trail comparing doxazosin and hydrochlorothiazide.

This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the alpha 1 antagonist, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I-Baseline; Phase II-Monotherapy Titration; Phase III-Combination Therapy Titration; and Phase IV-Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects. Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (-19 and -16 mm Hg); HCTZ (-22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.

Smoking cessation and arrhythmic death: the CAST experience. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators.

OBJECTIVES: This study was performed to assess the effect of cigarette smoking cessation on overall mortality and the incidence of arrhythmic death in the population of the Cardiac Arrhythmia Suppression Trial (CAST). BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death. Some of the adverse effects of smoking have been shown to dissipate with smoking cessation, but the time frame over which these changes occur and the population that stands to benefit have not been well delineated. CAST was a multicenter double-blind placebo-controlled study to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs in patients with left ventricular dysfunction after acute myocardial infarction would reduce the incidence of arrhythmic death. METHODS: Of 2,752 patients randomized to blinded therapy, 1,026 were smoking at the time of their baseline examination and completed a 4-month follow-up visit. Of these, 517 stopped smoking by the time of this visit ("quitters") and 509 continued to smoke ("smokers"). RESULTS: Over a mean follow-up period of slightly < 16 months, there were 17 arrhythmic deaths and 32 total deaths among the quitters versus 30 and 45, respectively, among the smokers; these differences were of marginal statistical significance. Most of the fatal events occurred in a group at high risk of ongoing ischemia: the 558 patients who did not have thrombolysis or undergo revascularization after their qualifying myocardial infarction. In this high risk cohort, smoking cessation greatly reduced the incidence of arrhythmic death and was associated with a statistically significant benefit in survival. CONCLUSIONS: Smoking cessation was accompanied by a marked reduction in arrhythmic death and overall mortality that achieved statistical significance in a high risk cohort. These data imply that smoking cessation is important in risk factor reduction in patients with advanced ischemic heart disease.

Circadian variations in cardiac disease: clinical implications. Current strategies for preventing MI, dysrhythmias, sudden death.

Myocardial infarction (MI), myocardial ischemia, ventricular dysrhythmias, and sudden cardiac death (SCD) occur most frequently in the morning, especially in the first few hours after awakening. Among individual patients, however, this pattern may vary widely. Peaks in heart rate, blood pressure, and platelet aggregability and a trough in fibrinolytic activity are thought to influence the morning onset of events. beta-Blockers may blunt the peak occurrence of MI, SCD, and ischemia. Some calcium channel blockers may modify the pattern of ischemia. Alternate-day therapy with 325 mg of aspirin has been shown to blunt the morning onset of MI. The efficacy of thrombolytics may be affected by daily fluctuations in fibrinolytic activity.

Relation between electrocardiography and echocardiography for left ventricular mass in mild systemic hypertension (results from Treatment of Mild Hypertension Study).

Clinical recognition of hypertensive cardiac involvement depends primarily on use of noninvasive methods. The performance of 8 electrocardiographic (ECG) criteria sets were compared with an echocardiographic standard in the treatment of Mild Hypertension Study. Electrocardiograms were computer processed to define the following ECG criteria sets: (1) Casale/Devereux, (2) Cornell product, (3) Cornell voltage, (4) 12-lead voltage product, (5) sum of 12-lead voltage, (6) Rautaharju, (7) Sokolow-Lyon, and (8) Romhilt-Estes. Echocardiographic left ventricular (LV) mass index was calculated by using the Penn convention on a biracial population of 834 men and women. Correlations between ECG and echocardiographic LV mass index were modest (<0.40). ECG-LV hypertrophy sensitivity at 95% specificity was < 34%. The Casale/Devereux ECG criteria showed the highest average sensitivity (17%) at 95% specificity for all race-sex groups. Whites had significantly higher correlation values than blacks. ECG correlations with LV mass index were consistently improved by including systolic blood pressure and body mass index. ECG criteria sets appear to be optimized for white men. The study findings confirm the poor ECG sensitivity and correlation with echocardiographic LV mass and suggest: (1) further refinement of ECG criteria alone in white men is unlikely to improve its relationship with LV mass; and (2) combining the electrocardiogram with other non-ECG variables or noninvasive measurements offers the best strategy for improving ECG sensitivity and its prognostic value.