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PubMed1987

Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus.

Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca2+ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca2+ transport, little appears to be known about its Ca2+ transporting capability in the diabetic myocardium. In this regard, we have examined the status of the cardiac sarcolemmal Ca2+ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection (55 mg/kg iv). Ca2+ pump activity assessed by measuring its Ca2+-stimulated adenosine triphosphatase and Ca2+-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca2+ pump is defective in the diabetic myocardium and may be involved in the altered Ca2+ transport of the heart during diabetes mellitus.

Adenosine Triphosphatases↗
PubMed2026

Sex Differences in Postoperative Recovery and Mortality After High-Risk Cardiac Surgery: A Propensity Score-Matched Post Hoc Analysis of the SUSTAIN-CSX Trial.

BACKGROUND: Sex-related differences after cardiac surgery remain controversial because women often present with higher baseline risk and complexity than men. We performed a post hoc propensity score-matched analysis of the SUSTAIN-CSX (Sodium Selenite Administration in Cardiac Surgery) trial to evaluate sex differences in mortality, postoperative complications, and recovery after high-risk cardiac surgery. METHODS: Of 1394 trial participants, 1386 had complete data. Women were matched 1:1 to men using nearest-neighbor propensity score matching based on age and European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), with exact matching on surgical category, yielding 327 female-male pairs. Prespecified sensitivity analyses adjusted for frailty, baseline hemoglobin, renal disease, left ventricular ejection fraction, previous myocardial infarction, preoperative medications, and baseline creatinine. RESULTS: In the primary matched analysis, 180-day survival did not differ between women and men (log-rank P=0.086; unadjusted hazard ratio, 1.80 [95% CI, 0.91-3.55]; P=0.091). In descriptive matched comparisons, women had numerically longer intensive care unit stay (median, 3 days [quartile 1, quartile 3 (Q1, Q3)=1, 6 days] versus 2 days [Q1, Q3=1, 5 days]) and hospital stay (median, 10 days [Q1, Q3=7, 18 days] versus 9 days [Q1, Q3=6, 16 days]; P=0.292), whereas major postoperative complications were similar. In adjusted sensitivity analyses accounting for the matched design and residual imbalance, female sex remained associated with longer intensive care unit stay (adjusted incidence rate ratio [IRR], 1.8 [95% CI, 1.2-2.9]; P=0.009) and hospital stay (adjusted IRR, 1.4 [95% CI, 1.0-1.9]; P=0.031). Mortality sensitivity analyses were model-dependent. CONCLUSIONS: In this propensity score-matched cohort of high-risk cardiac surgery patients, women showed a longer postoperative recovery trajectory in adjusted analyses, whereas mortality findings were sensitive to model specification and should be interpreted cautiously. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002247.

Aged↗
PubMed2006

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus. METHODS: MEDLINE (from inception to November 2005) and the Cochrane Controlled Trials Register (including Issue 3, 2005) were searched for randomised controlled trials comparing therapy with fibrates to placebo in patients with type 2 diabetes mellitus. Electronic searches were supplemented by manual searching of reference lists, reviews, conference abstracts and specialist journals. Incidence rate ratios (IRRs) were estimated using a fixed effects model. The primary endpoint was the IRR for coronary heart disease (CHD) events (a combination of non fatal myocardial infarction and death due to CHD). Secondary endpoints included: (1) death due to CHD; (2) fatal and non fatal myocardial infarction; and (3) fatal and non fatal stroke. RESULTS: Eight trials and 12 249 patients with type 2 diabetes were included in the analyses. A total of 924 CHD events (418 and 506 in the treatment and placebo groups, respectively) occurred during a follow up of 60 395 person-years (30 106 and 30 289 in treatment and placebo groups). The combined IRR for CHD events was 0.84 (95% confidence interval [CI] 0.74-0.96, p = 0.008). The numbers needed to treat (NNTs) to prevent one CHD event over 10 years were nine and 26 for patients with and without pre-existing CHD, respectively. IRRs for death due to CHD, myocardial infarction and stroke were 0.96 (95% CI 0.77-1.20, p = 0.73), 0.88 (95% CI 0.69-1.12, p = 0.30) and 0.87 (95% CI 0.73-1.05, p = 0.14), respectively. Larger benefits were found when restricting the analysis to trials that were not confounded by unequal provision of additional lipid-lowering therapy. CONCLUSIONS: Fibrates are associated with a substantial reduction of CHD events, but their exact role in lipid lowering treatment of patients with type 2 diabetes mellitus remains to be defined.

Cardiovascular Diseases↗
PubMed2001

[Are newer antihypertensive agents better than the older ones? Results of trials (CAPPP, STOP-2, NORDIL, INSIGHT and ALLHAT) with newer antihypertensive agents].

Until recently, no morbidity-mortality study had examined the effects of "newer" drugs, like angiotensin-converting enzyme inhibitors, calcium antagonists, and alpha-blockers compared to "old", but well-proven, thiazide diuretics, and beta-blockers in the treatment of essential hypertension. The prospective and randomised clinical trials, CAPPP, STOP-2, NORDIL, INSIGHT, and one arm of ALLHAT, with a total of about 58,000 middle-aged or elderly hypertensive patients have now been published. The primary outcome, composite cardiovascular (CV) death, cerebral stroke, and myocardial infarction, or composite fatal coronary heart disease and myocardial infarction, was the same, irrespective of the drug in all trials. Thus, prevention of CV complications depends on the lowering of blood pressure with well-tolerated medication, irrespective of class.

Adult↗
PubMed1988

[Nuclear medicine functional diagnosis of the myocardium using (123) I-heptadecanoic acid].

On the basis of the results which we obtained having performed 25 examinations on 15 patients with angina pectoris syndrome, myocardial infarctions and condition after bypass operation the preparation 123I hepatadecanoic acid produced in the Central Institute for Nuclear Research Rossendorf is very well suited for the scintigraphic demonstration of the myocardium. Moreover it is possible to recognize selectively diagnostically interesting regions with different radioactivity intake, retention and elimination of the radiopharmacon pharmacon and with the help of quantitative parameters to characterize concerning the metabolic efficiency. We consider the 123I hepatadecanoic acid suitable for the clinical use in establishing the global and regional metabolic efficiency of the myocardium. It is very well to be used for the primary diagnostics and represents an evident diagnostic remedy for the assessment of the course of myocardial diseases and the success of therapy.

Adult↗
PubMed1993

Beta-blocking agents with vasodilator activity.

Use of non-selective beta-blockers: Non-selective beta-blockers reduce blood pressure by reducing cardiac output. They have a proven record of efficacy, alone or in combination with other drug classes, in the treatment of hypertension, ischemic heart disease and some tachyarrhythmias. They have also proved effective in the primary and secondary prevention of myocardial infarction. However, adverse effects include increased peripheral resistance, limitation of exercise tolerance, and bradyarrhythmia, cold extremities and bronchoconstriction in susceptible patients. Effects of beta 1-selective blockers: beta 1-Selective antagonists cause less vasoconstriction and less bronchoconstriction than non-selective beta-blockers, but the reduction in cardiac output may still activate a sympathetically mediated increase in peripheral resistance. beta 1-blockers with beta 2 agonist activity are vasodilatory because they activate postsynaptic beta 2 receptors on vascular smooth muscle cell membranes, via the formation of cyclic AMP. Non-selective beta-blockers with alpha 2-adrenoceptor blocking activity: Non-selective beta-adrenoceptor blockers with alpha 1-adrenoceptor blocking activity, such as carvedilol, labetalol, medroxalol and bucindolol, combine the advantages of beta- and alpha 1-blockade, including peripheral vasodilation. As an example of this class of agent, carvedilol has been shown to be effective in the treatment of hypertension by reducing peripheral resistance. There are some indications, still to be confirmed, that it improves left ventricular diastolic function and causes regression of left ventricular hypertrophy, and that it may be useful in the treatment of some patients with congestive heart failure or arrhythmia. In animal models of myocardial ischemia, carvedilol has proved to be cardioprotective.

Adrenergic alpha-Antagonists↗
PubMed1990

Secondary enterovirus infection in the murine model of myocarditis. Pathologic and immunologic aspects.

Enteroviruses are implicated as etiologic agents in the inflammatory diseases myocarditis and polymyositis. In this report, we show that a previous enterovirus exposure in mice can influence development of myocardial inflammation with a second enteroviral exposure. Inoculation of 25-day-old male C3H/HeJ mice with 10(3) or 10(5) plaque-forming units (PFU) of infectious or ultra violet (UV)-inactivated coxsackievirus B2 (CVB2), followed by inoculation 28 days later with 10(5) PFU of a myocarditic variant of coxsackievirus B3 (CVB3-m) results in more intense myocardial inflammation and injury than is seen in age-matched mice inoculated with CVB3-m alone. More severe disease occurs with the lower primary dose of CVB2. Neutralizing antibody to CVB2 is detected early after primary inoculation and neutralizing antibody to CVB3 is first detected 5 days after secondary inoculation. In vitro proliferation of splenocytes from mice inoculated with one or both viruses occurs in response to both CVB2 and CVB3 antigens. We recently demonstrated that murine T cells are capable of recognizing an enterovirus group antigen. Thus cell-mediated immune responses to a conserved antigenic epitope(s) among the enteroviruses may be involved in the exacerbation of myocardial inflammatory disease during a second enterovirus infection. The secondary infection model described here may more accurately mirror virus-induced myocarditis in the human population because the majority of adults have been exposed to several enteroviruses before induction of disease.

Animals↗
PubMed2001

High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease.

Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.

Algorithms↗
PubMed2001

Primary care diabetes. What options are there?

BACKGROUND: The recognised incidence of type 2 diabetes mellitus is increasing dramatically and the vital importance of good diabetes control in patients with both type 1 and type 2 diabetes is now well established. Weight reduction and oral hypoglycaemic therapy has been accompanied by new drug treatment options in type 2 diabetes, while refinements in insulin delivery are more relevant for patients with type 1 diabetes. OBJECTIVE: To review currently available drug therapies and management strategies for type 2 diabetes, and optimal insulin treatment regimens for type 1 diabetes. DISCUSSION: Weight reduction and regular exercise remain major lifestyle intervention priorities in type 2 diabetes. Metformin should be used early in overweight patients, and sulphonylureas as additive therapy. Acarbose, orlistat and the thiazolidinediones all have potential roles in the treatment of type 2 diabetes where cardiovascular risk factor reduction is also of vital importance. Insulin analogues and continuous subcutaneous insulin infusion via insulin pumps will help to optimise insulin replacement regimens for patients with type 1 diabetes mellitus.

Clinical Protocols↗
PubMed1992

[Role of coronary collateral circulation in the compensation of disorders of myocardial perfusion and left ventricular function in patients with newly appearing angina pectoris].

The myocardial perfusion and left ventricular function were evaluated by bicycle ergometry and myocardial scintigraphy in 23 patients with primary angina taking into account the status of coronary collateral circulation in response to stenotic and occlusive atherosclerosis. In addition to severe occlusive disease of the coronary bed, most patients had significant disturbances of myocardial perfusion and left ventricular function, which were detected during exercise tests. In patients with compensatory collateral circulation in the coronary bed, such disturbances were less marked than in those without anastomoses. However collateral coronary circulation cannot be regarded to be of real value as it compensates impaired perfusion incompletely, but in some cases it can result in impaired myocardial vascularization apparently due to the steal syndrome.

Adult↗
PubMed2005

Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study.

As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is known about the prognostic impact of baseline ADMA determination. In a prospective cohort of 1908 patients with coronary artery disease, we assessed baseline serum concentration of ADMA in 1874 consecutive patients with coronary artery disease. One hundred fourteen individuals developed the primary end point of death from cardiovascular causes or nonfatal myocardial infarction during a mean follow-up of 2.6+/-1.2 years. Median concentrations of ADMA levels were higher among individuals who subsequently developed the primary end point than among those who did not (0.70 versus 0.63 micromol/L; P<0.001). The risk of future cardiovascular event was associated with increasing thirds of baseline ADMA (P for trend, <0.001) such that individuals in the highest third at entry had a hazard ratio 2.48 times higher than those in the lowest third (95% confidence interval, 1.52 to 4.06; P<0.001). This relationship remained nearly unchanged after adjustment for most potential confounders. Prediction models that simultaneously incorporated ADMA, B-type natriuretic peptide, C-reactive protein, and creatinine in addition to traditional risk factors revealed B-type natriuretic peptide (hazard ratio, 1.96; 95% confidence interval, 1.3 to 3.0; P=0.002) and ADMA (hazard ratio, 1.90; 95% confidence interval, 1.3 to 2.8; P=0.001) as the strongest risk predictors. High levels of baseline ADMA independently predict future cardiovascular risk. ADMA has prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies.

Adult↗
PubMed1992

Reoperation for recurrent coronary artery disease--a ten year experience.

The need for reoperation caused by recurrence of coronary artery disease is becoming increasingly common. Although reoperation is more difficult and time-consuming, with careful surgical technique it can be carried out with the same mortality as that described by many units for primary coronary artery bypass grafting (1.2-2.0%). In the 172 patients described here, who had coronary artery reoperations between 1981 and 1990, there were two in-hospital deaths (1.2%). There were three postoperative bleeds which required return to theatre. No patient suffered a postoperative neurological deficit or postoperative myocardial infarction. These reoperations comprised 6.9% of the 2497 coronary artery operations carried out in the same period. Follow-up disclosed eight late deaths, from five-62 months after operation; all survivors claim to be symptomatically improved. Consideration should be given to the potential problems of reoperation when carrying out primary myocardial revascularisation.

Adult↗
PubMed2006

[Primary prevention of ischemic heart disease in middle-aged men living in Prague: results of twenty-year research].

INTRODUCTION: Ischemic Heart Disease (IHD) represents the most frequent cause of mortality and morbidity in the Czech Republic. The aim of this study is to analyze long-term mortality of cardiovascular disease (CVD), identify its predictors and verify the validity of Framingham risk function for Czech patients. DESIGN AND METHODS: The twenty-year study (STULONG) of primary prevention of risk factors of atherosclerosis in 1419 men aged 38 to 53 years living in Prague was started in 1975. RESULTS: CVD mortality analysis showed a higher risk of death for heavy smokers vs. non-smokers or light smokers (p < 0.0001), hypertensive patients vs. patients with normal blood pressure (p < 0.0001), men with hypercholesterolemia vs. men with normal cholesterol level (p = 0.0432), and a lower risk for university graduates vs. men with elementary education (p = 0.0006). Between 1980 and 1984, age-specific CVD mortality rates of men from STULONG study were higher (p = 0.0132) than national CVD mortality rates; between 1985 and 1994, they were insignificantly lower. Framingham risk function underestimated absolute ten-year risk of IHD in all risk quintiles (p < 0.0001) with discrimination of 63%. CONCLUSION: CVD mortality observed within STULONG study was significantly affected by known risk factors (hypertension, smoking, hypercholesterolemia, lower education); Framingham risk function underestimated absolute ten-year risk of IHD.

Coronary Artery Disease↗
PubMed1986

[Integral indices of the automatically reproduced spatial QRS loop in the diagnosis of different forms of myocardial hypertrophy].

A total of 249 patients with arterial hypertension taking a variety of clinical forms, primary pulmonary hypertension, dilatation cardiomyopathy, congenital heart diseases with secondary pulmonary hypertension were examined and allocated to 3 groups: 125 patients with left-ventricular hypertrophy (LVH) (group 1); 44 patients with right-ventricular hypertrophy (RVH) (group 2), and 80 patients with combined hypertrophy of both ventricles (CH). Eighty-one normal subjects were taken as controls. New parameters of diagnostic significance were identified by automated reproduction of vectorcardiographic spatial QRSxyz loop (the Macfee-Parungao system) and computer analysis of vectorcardiographic parameters, that improve electrocardiographic diagnosis of cardiac hypertrophies, as compared to the conventional criteria, bringing its accuracy to 88.8% for LVH, 100% for RVH, and 45% for CH. Typical features of myocardial hypertrophy at large are increased area enclosed by the spatial loop (SQRS greater than 3.4 mV2) and/or increased mean vector (LQRSxyz greater than 0.76 mV), while Lx greater than 0.6 mV and/or Lz less than -0.4 mV were specific for LVH; Lx less than 0.05 mV was specific for RVH, and the H angle ranging from -70 degrees to -140 degrees or H of -60 degrees to -140 degrees at Lz less than 1.1 mV, or -50 degrees to -140 degrees at Lz less than 1.5 mV were specific for CH.

Cardiomegaly↗
PubMedDate not supplied

Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.

BACKGROUND: Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients. We aimed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk. METHODS: We did a randomised, double-blind, placebo-controlled trial to compare aspirin (75 mg/day) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day. Duration of treatment and follow-up was 18 months. The primary endpoint was a composite of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation for acute ischaemia (including rehospitalisation for transient ischaemic attack, angina pectoris, or worsening of peripheral arterial disease). Analysis was by intention to treat, using logrank test and a Cox's proportional-hazards model. FINDINGS: 596 (15.7%) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 (16.7%) in the clopidogrel alone group (relative risk reduction 6.4%, [95% CI -4.6 to 16.3]; absolute risk reduction 1% [-0.6 to 2.7]). Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 [2.6%] vs 49 [1.3%]; absolute risk increase 1.3% [95% CI 0.6 to 1.9]). Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality. INTERPRETATION: Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events. However, the risk of life-threatening or major bleeding is increased by the addition of aspirin.

Aged↗
PubMed2000

Pravastatin therapy and the risk of stroke.

BACKGROUND: Several epidemiologic studies have concluded that there is no relation between total cholesterol levels and the risk of stroke. In some studies that classified strokes according to cause, there was an association between increasing cholesterol levels and the risk of ischemic stroke and a possible association between low cholesterol levels and the risk of hemorrhagic stroke. Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have suggested that these agents may reduce the risk of stroke. METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in Ischaemic Disease study), we compared the effects of pravastatin on mortality due to coronary heart disease (the primary end point) with the effects of placebo among 9014 patients with a history of myocardial infarction or unstable angina and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per liter). Our goal in the present study was to assess effects on stroke from any cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There were 419 strokes among 373 patients over a follow-up period of six years. A total of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of unknown type. Among the patients given placebo, the risk of stroke was 4.5 percent, as compared with 3.7 percent among those given pravastatin (relative reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent; P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given placebo, as compared with 3.4 percent of those given pravastatin (reduction in risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS: Pravastatin has a moderate effect in reducing the risk of stroke from any cause and the risk of nonhemorrhagic stroke in patients with previous myocardial infarction or unstable angina.

Adult↗
PubMedDate not supplied

[The structural-functional properties of the thrombocytes in patients with a history of a myocardial infarct].

Functional state and morphological features of platelets were studied in patients with ischemic heart disease 3-24 months following the primary infarction and reinfarction. The studies made pointed to considerable changes in the structure, metabolism and reactivity of platelets. Chronic exposure to irritant factors makes for the depletion and destabilization of blood plates, their adhesive properties and ability to store and catabolize biogenic amines being upset, the destructive changes of glycocalix having a most pronounced impact on the platelet reactivity. The structural and functional disturbances revealed in the thrombocyte homeostasis have been found to correlate with the clinical course of the illness.

Blood Platelets↗
PubMed1993

[Fatty acid composition of plasma lipids in hyperlipidemia associated with ischemic heart disease].

The authors compared plasma lipid and lipoprotein values and the fatty acid composition in plasma lipids of a group of 38 men with primary hyperlipoproteinaemia (HLP) type II B and IV with a history of myocardial infarction (IM) and in a control group of 63 men with the same type of HLP without a history of ischaemic heart disease (IHD). Hyperlipidaemic subjects after IM differed from controls by the apolipoprotein (apo) B concentration in LDL lipoproteins and by the composition of fatty acids in plasma phosphatidylcholine (PC) and triglycerides (TG). In the discriminating function which makes it possible in the given group of patients to classify correctly hyperlipidaemic subjects after IM and without detectable IHD the independent variables are apo-B concentration in LDL, apo-A-I in plasma, eicosapentaenoic acid in TG, gamma-linolenic acid in cholesterol esters and stearic and oleic acid in PC. These findings confirm the practical value of assessment of apolipoproteins for detection of hyperlipidaemic subjects with a specially high risk of IHD and indicate also the role of essential FA in the pathogenesis of IM.

Fatty Acids↗