lisinopril and Heart-Diseases

Historically, blood pressure control in Hispanics has been considerably less than that of non-Hispanic whites and blacks. We compared determinants of blood pressure control among Hispanic white, Hispanic black, non-Hispanic white, and non-Hispanic black participants (N=32 642) during follow-up in a randomized, practice-based, active-controlled trial. Hispanic blacks and whites represented 3% and 16% of the cohort, respectively; 33% were non-Hispanic black and 48% were non-Hispanic white. Hispanics were less likely to be controlled (<140/90 mm Hg) at enrollment, but within 6 to 12 months of follow-up, Hispanics had a greater proportion <140/90 mm Hg compared with non-Hispanics. At 4 years of follow-up, blood pressure was controlled in 72% of Hispanic whites, 69% of Hispanic blacks, 67% of non-Hispanic whites, and 59% of non-Hispanic blacks. Compared with non-Hispanic whites, Hispanic whites had a 20% greater odds of achieving BP control by 2 years of follow-up (odds ratio: 1.20; 95% CI: 1.10 to 1.31) after controlling for demographic variables and comorbidities, Hispanic blacks had a similar odds of achieving BP control (odds ratio: 1.04; 95% CI: 0.86 to 1.25), and non-Hispanic blacks had a 27% lower odds (odds ratio: 0.73; 95% CI: 0.69 to 0.78). We conclude that in all patients high levels of blood pressure control can be achieved with commonly available medications and that Hispanic ethnicity is not associated with inferior control in the setting of a clinical trial in which hypertensive patients had equal access to medical care, and medication was provided at no cost.

Topics: Aged; Amlodipine; Antihypertensive Agents; Atenolol; Black People; Blood Pressure; Canada; Chlorthalidone; Clonidine; Double-Blind Method; Doxazosin; Female; Heart Diseases; Hispanic or Latino; Humans; Hydralazine; Hypertension; Hypolipidemic Agents; Lisinopril; Male; Middle Aged; Puerto Rico; Reserpine; Treatment Outcome; United States; United States Virgin Islands; White People

To investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and beta-blockers would beneficially affect the measured indices.. In the cross-sectional analysis, plasma viscosity (P=0.001), fibrinogen (P=0.02), vWF (P<0.0001), and soluble P-selectin (P<0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P<0.05). Plasma viscosity (P=0.009) and fibrinogen (P=0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III-IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P=0.016) and vWF (P=0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of beta-blocker therapy, apart from a rise in mean platelet count (P<0.001).. Abnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of beta-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Arrhythmia, Sinus; Blood Platelets; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Endothelium, Vascular; Female; Fibrinogen; Heart Diseases; Hematocrit; Humans; Lisinopril; Male; Middle Aged; P-Selectin; Platelet Count; Regression Analysis; Rheology; Sex Characteristics; Solubility; Statistics, Nonparametric; Viscosity; von Willebrand Factor

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Echocardiography; Female; Heart Diseases; Humans; Incidence; Lisinopril; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Nitroglycerin; Thrombolytic Therapy; Thrombosis; Vasodilator Agents

Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague-Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX-treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Catalase; Disease Models, Animal; Doxorubicin; Electrocardiography; Heart Conduction System; Heart Diseases; Heart Rate; Lisinopril; Male; Malondialdehyde; Myocytes, Cardiac; Rats, Sprague-Dawley; Ubiquinone

Topics: Antihypertensive Agents; Carbohydrate Metabolism; Clinical Trials as Topic; Diuretics; Drug Therapy, Combination; Drugs, Generic; Heart Diseases; Humans; Hypertension; Hypokalemia; Indapamide; Lipid Metabolism; Lisinopril; Stroke; Thiazides

Topics: Aminopeptidases; Angiotensin-Converting Enzyme Inhibitors; Animals; Collagen; Fibroblasts; Fibrosis; Heart Diseases; Humans; Hypertension; Leucine; Lisinopril; Myocardium; Peptidyl-Dipeptidase A; Protease Inhibitors

Childhood survivors of cancer who are treated with anthacycline chemotherapy, such as doxorubicin (DOX), can develop late-onset cardiomyopathy years after chemotherapy. The mechanism(s) for progression of anthracycline cardiotoxicity to late cardiomyopathy is unknown. Because angiotensin II has been implicated in the progression of other cardiomyopathies, this investigation was undertaken to determine whether treatment with an angiotensinconverting enzyme (ACE) inhibitor, lisinopril, reduces the time-dependent effects of doxorubicin on cardiac gene expression and myocellular apoptosis. A single dose of saline (control) or doxorubicin (DOX treated; 2 mg/kg iv) was administered to rabbits. Control and DOX-treated groups were also subgrouped to receive lisinopril and designated as lisinopril or DOX + lisinopril, respectively (1 mg/kg/d oral), for 10 wk. Histopathology, as determined at the light and ultrastructural level, was consistent with a reduced number of cardiomyocytes relative to interstitial cells in the left ventricle (LV) of the DOX-treated group compared with control and DOX + lisinopril groups. Gene expression of the pro-atrial naturetic peptide (ANP), quantified by steady-state messenger ribonucleic acid (mRNA) levels with reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blotting, increased approx 12-fold (n = 10; p < 0.05) in the LV of DOX-treated groups compared to control and DOX + lisinopril groups. Increased ANP mRNA expression following doxorubicin dosing was localized predominantly in ventricular myocytes by in situ hybridization. Deoxyribonucleic acid (DNA) fragmentation, determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling), was increased in both DOX-treated and DOX + lisinopril groups compared to the control group. Lisinopril prevented both late-onset increased ventricular ANP expression and subsequent DOX-induced myocyte loss. The authors speculate that these protective effects of lisinopril are related to reduced ANP expression and myocyte loss, the latter possibly mediated by effects on myocellular apoptosis.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antibiotics, Antineoplastic; Apoptosis; Blotting, Southern; Doxorubicin; Female; Gene Expression; Heart Diseases; Heart Ventricles; Immunohistochemistry; In Situ Hybridization; Infusions, Intravenous; Lisinopril; Rabbits; Reverse Transcriptase Polymerase Chain Reaction

This study was performed to determine whether angiotensin (Ang) II-forming enzymes, angiotensin converting enzyme (ACE) and chymase might contribute to the development of adriamycin-induced cardiomyopathy in hamsters. Hamsters were administered adriamycin (2.0 mg/kg per day, i.p.) three times weekly for 2 weeks. In the ACE inhibitor-treated group, the hamsters received lisinopril (20 mg/kg per day, p.o.) for 2 weeks after the last injection of adriamycin. The 4-week mortality rates of the vehicle- and ACE inhibitor-treated hamsters were 44% and 12%, respectively. In comparison to the age-matched hamsters used as the control hamsters, a significant decrease in cardiac function and a significant increase in the ratio of the heart weight to the body weight were observed in the vehicle hamsters. Cardiac ACE activity, but not the chymase activity, in the vehicle hamsters was significantly increased in comparison to that in the control hamsters. In the ACE inhibitor-treated group, the increased ACE activity was reduced significantly, and the cardiac hypertrophy and dysfunction were improved significantly. In adriamycin-induced cardiomyopathic hamsters, cardiac ACE activity was increased and ACE inhibition significantly improved cardiac function and survival rate, indicating that cardiac ACE, but not the chymase, plays the pivotal role in the development of the adriamycin-induced cardiomyopathy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Cardiomyopathies; Chymases; Cricetinae; Doxorubicin; Drug Interactions; Heart Diseases; Hemodynamics; Lisinopril; Male; Organ Size; Peptidyl-Dipeptidase A; Serine Endopeptidases; Survival Rate

We evaluated the role of SH-groups in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH-group) versus lisinopril (no SH-group), or N-acetylcysteine (only SH-group) in myocardial infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium-dependent and -independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS-inhibitor L-NMMA to determine NO-contribution. Total dilatation after receptor-dependent stimulation with acetylcholine (ACh) was attenuated (-49%, P<0.05) in untreated MI (n=11), compared to control rats with no-MI (n=8). This was in part due to impaired NO-contribution in MI (-50%, P<0.05 versus no-MI). At the same time the capacity for generation of biologically active NO after receptor-independent stimulation with A23187 remained intact. Chronic treatment with n-acetylcysteine (n=8) selectively restored NO-contribution in total dilatation to ACh. In contrast, both ACE-inhibitors fully normalized total dilatation to ACh, including the part mediated by NO (no significant differences between zofenopril (n=10) and lisinopril (n=8)). Zofenopril, but not lisinopril, additionally potentiated the effect of endogenous NO after A23187-induced release from the endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin (+22%) and sodium nitrite (+36%) (for all P<0.05 versus no-MI). We conclude that ACE-inhibition with a SH-group has a potential advantage in improvement of endothelial dysfunction through increased activity of NO after release from the endothelium into the vessel wall. Furthermore, this is the first study demonstrating the selective normalizing effect of N-actylcysteine on NO-contribution to ACh-induced dilatation in experimental heart failure.

Topics: Acetylcholine; Acetylcysteine; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Calcimycin; Captopril; Endothelium, Vascular; Heart Diseases; In Vitro Techniques; Lisinopril; Male; Myocardial Infarction; Nitrates; Nitrites; Nitroglycerin; omega-N-Methylarginine; Rats; Rats, Wistar; Sodium Nitrite; Sulfhydryl Compounds; Vasodilation; Vasodilator Agents

The angiotensin converting enzyme inhibitor, lisinopril, was studied in a cryo-injury model of chronic heart failure. This model is characterized by a progressive decrease in cardiac output starting six weeks after cryo-injury to a 30% decrease in cardiac output 10 weeks after injury. Although histological damage to the myocardial tissue, particularly in the epicardial area, was observed, no significant changes occurred in body weight, mean arterial blood pressure, heart rate or central venous pressure. Daily intraperitoneal injection of 3 mg/kg lisinopril was instituted starting four weeks after injury for a duration of six weeks. Lisinopril completely restored the cardiac output to normal values at the end of this six week period. Thus, converting enzyme inhibition appears to be an effective therapeutic agent in this model of chronic cardiac failure.

Topics: Animals; Cardiac Output; Cryosurgery; Disease Models, Animal; Enalapril; Heart Diseases; Heart Ventricles; Hemodynamics; Lisinopril; Male; Rats; Rats, Inbred Strains