Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine

Renal and hemodynamic responses to bumetanide in hypertension: Effects of nitrendipine. The effects of a calcium antagonist on the response to a loop diuretic were tested in eight hypertensive patients while they received 120mmol · 24hr-1 of dietary Na. Nitrendipine (N; 20 mg) or placebo (P) was administered twice daily for five days and bumetanide (B; 1 mg, i.v.) for the last three days of each period. Cardiac index (CI) was measured during tilt. B alone significantly (P < 0.05; N = 7) reduced CI and increased total peripheral resistance; N prevented these effects of B. Neither drug altered BP consistently. Although three days of B increased plasma renin activity (PRA) during P and N, it increased plasma aldosterone (PAldo) only during P (P, 4.4 ± 1.3 to 7.6 ± 1.0; P < 0.05. N, 5.7 ± 1.3 to 6.0 ± 1.3; pg · liter-1; NS). B increased Na excretion without changing GFR or RPF; this was followed by 18 hours of decreased renal Na excretion. These actions were unchanged by N. N did not change the cumulative excretion of B (P, 268 ± 35 vs. N, 217 ± 21 µg) or the relationship between Na excretion and the log of B excretion. However, Na excretion was increased (P < 0.05) by 40 to 60% in the six hour period following the first two doses of N. Therefore, the cumulative Na balance was more negative during five days of N (P, -47 ± 17 vs. N, -108 ± 24 mmol; P < 0.05). The effect of N and B on Na balance were independent. In conclusion, short-term administration of N: 1) increases CI and reduces TPRI in the post-diuretic state; 2) blunts B-induced increase in PAldo without modifying the rise in PRA; 3) does not change B kinetics or dynamics or the post-diuretic period of renal Na retention; 4) causes negative Na balance which is additive with that produced by B

Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy

OBJECTIVES To assess the relation of left ventricular (LV) and left atrial (LA) dimensions, ejection fraction (EF) and LV mass to subsequent clinical outcome of patients with LV dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry and Trials. BACKGROUND Data are lacking on the relation of LV mass to prognosis in patients with LV dysfunction and on the interaction of LV mass with other measurements of LV size and function as they relate to clinical outcome. METHODS A cohort of 1,172 patients enrolled in the SOLVD Trials (n = 577) and Registry (n = 595) had baseline echocardiographic measurements and follow-up for 1 year. RESULTS After adjusting for age, New York Heart Association (NYHA) functional class, Trial vs. Registry and ischemic etiology, a 1-SD difference in EF was inversely associated with an increased risk of death (risk ratio, 1.62; p = 0.0008) and cardiovascular (CV) hospitalization (risk ratio, 1.59; p = 0.0001). Consequently, the other echo parameters were adjusted for EF in addition to age, NYHA functional class, Trial vs. Registry and ischemic etiology. A 1-SD difference in LV mass was associated with increased risk of death (risk ratio of 1.3, p = 0.012) and CV hospitalization (risk ratio of 1.17, p = 0.018). Similar results were observed with the LA dimension (mortality risk ratio, 1.32; p 5.0 cm was associated with increased mortality only. A protective effect of EF was noted in patients with LV mass ≥298 g (those in the group with EF >35% had lower mortality) but not in the group with LV mass 35% fared better) but not in the group with LV mass <298 g. These data support the development and use of drugs that can inhibit hypertrophy or alter its characteristics

Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy

OBJECTIVES To assess the relation of left ventricular (LV) and left atrial (LA) dimensions, ejection fraction (EF) and LV mass to subsequent clinical outcome of patients with LV dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry and Trials. BACKGROUND Data are lacking on the relation of LV mass to prognosis in patients with LV dysfunction and on the interaction of LV mass with other measurements of LV size and function as they relate to clinical outcome. METHODS A cohort of 1,172 patients enrolled in the SOLVD Trials (n = 577) and Registry (n = 595) had baseline echocardiographic measurements and follow-up for 1 year. RESULTS After adjusting for age, New York Heart Association (NYHA) functional class, Trial vs. Registry and ischemic etiology, a 1-SD difference in EF was inversely associated with an increased risk of death (risk ratio, 1.62; p = 0.0008) and cardiovascular (CV) hospitalization (risk ratio, 1.59; p = 0.0001). Consequently, the other echo parameters were adjusted for EF in addition to age, NYHA functional class, Trial vs. Registry and ischemic etiology. A 1-SD difference in LV mass was associated with increased risk of death (risk ratio of 1.3, p = 0.012) and CV hospitalization (risk ratio of 1.17, p = 0.018). Similar results were observed with the LA dimension (mortality risk ratio, 1.32; p 5.0 cm was associated with increased mortality only. A protective effect of EF was noted in patients with LV mass ≥298 g (those in the group with EF >35% had lower mortality) but not in the group with LV mass 35% fared better) but not in the group with LV mass <298 g. These data support the development and use of drugs that can inhibit hypertrophy or alter its characteristics

Exercise-induced hypoxemia in heart transplant recipient

AbstractObjectives. The purpose of this study was to determine whether heart transplantation has an adverse effect on pulmonary diffusion and to investigate the potentially deleterious effects of impaired pulmonary diffusion on arterial blood gas dynamics during exercise in heart transplant reciplents.Background. Abnormal pulmonary diffusing capacity is reported in patients after orthotopic heart transplantation. Abnormal diffusion may be caused by cyclosporlne or by the persistence of preexisting conditions known to adversely affect diffusion, such as congestive heart failure and chronic obstructive pulmonary disease.Methods. Eleven patients (mean age 50 ± 14 years) performed pulmonary function tests 3 ± 1 months before and 18 ± 12 (mean ± SD) months after heart transplantation. Transplant patients were assigned to groups with diffusion > 70% (n = 5) or diffusion < 70% of predicted values (n = 5). The control group and both subsets of patients performed 10 min of cycle exercise at 40% and 70% of peak power output. Arterial blood gases were drawn every 30 s during the 1st 5 min and at 6, 8 and 10 min.Results. Significant improvements in forced vital capacity (17,4%), forced expiratory volume in 1 s (11.7%) and diffusion capacity (6.6%) occurred in the patients; however, posttransplantation vital capacity, forced expiratory volume and diffusion were lower (p ≤ 0.05) compared with values in 11 control subjects. Changes in blood gases were similar among groups at 40% of peak power output. At 76% of peak power output, arterial blood gases and pH were significantly (p ≤ 0.05) lower in transplant patients with low diffusion (arterial oxygen pressure 15 to 38 mm Hg below baseline) than in patients with normal diffusion and control subjects. Cardiac index did not differ (p ≥0.05) between transplant patients with noramal and low diffusion at rest or during exercise. Posttransplantation mean pulmonary artery pressure was significantly related to exercise-induced hypoxemia (r = 0.71; p = 0.03).Conclusions. Abnormal pulmonary diffusion observed in patients before heart transplantation persists after transplantation with or without restrictive or obstructive ventilatory defects. Heart transplant recipients exprience exercise-induced hypoxemia when diffusion at rest is < 70% of predicted. Our data also suggest that abnormal pulmonary gas exchange possibly contributes to diminished peak oxygen consumption in some heart transplant recipients; however, direct testing of this hypothesis was beyond the scope of the present study. This possibility needs to be investigated further

Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results

Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women

Objective: To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women. Design and Methods Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up. Results: Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusion: Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease

Impact of cyclooxygenase inhibitors in the Women\u27s Health Initiative hormone trials: secondary analysis of a randomized trial

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women\u27s Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women\u27s Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women\u27s Health Initiative hormone trial results

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women\u27s Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratioor =2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL rati

Social isolation and incident heart failure hospitalization in older women: Women\u27s health initiative study findings

Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women\u27s Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through 2018. We conducted a mediation analysis to examine depressive symptoms as a potential mediator and further examined effect modification by age and race and ethnicity. Incident HF requiring hospitalization was the main outcome. Social isolation was a composite variable based on marital/partner status, religious ties, and community ties. Depressive symptoms were assessed using CES-D (Center for Epidemiology Studies-Depression). Over a median follow-up of 15.0 years, we analyzed data from 36 457 women, and 2364 (6.5%) incident HF cases occurred; 2510 (6.9%) participants were socially isolated. In multivariable analyses adjusted for sociodemographic, behavioral, clinical, and general health/functioning; socially isolated women had a higher risk of incident HF than nonisolated women (HR, 1.23; 95% CI, 1.08-1.41). Adding depressive symptoms in the model did not change this association (HR, 1.22; 95% CI, 1.07-1.40). Neither race and ethnicity nor age moderated the association between social isolation and incident HF. Conclusions Socially isolated older women are at increased risk for developing HF, independent of traditional HF risk factors. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00000611