Systemic Correlates of Angiographic Coronary Artery Disease

Coronary angiography allows a direct evaluation of coronary anatomy. The aim of the present investigation was to search for correlations between the magnitude of coronary artery disease, as assessed by angiography, and a number of systemic parameters. A group of 116 patients (80 male, 36 female) with coronary heart disease diagnosed by angiography, aged 62.0±10.5 years, was the subject of an observational study. Correlation and linear regression analysis using coronary artery disease burden (CADB - sum of the percentage of the luminal stenosis encountered in all the lesions of the coronary arterial trees) as dependent variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular filtration rate and body mass index as independent variables, were carried out. Significant correlation values versus CADB were seen with age (r 0.19, p 0.04), uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear regression analysis, yielding a global significance level of 0.002, showed a significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among several systemic parameters studied, plasma glucose was found to be correlated to coronary artery atherosclerosis lesions

The age of randomized clinical trials: three important aspects of randomized clinical trials in cardiovascular pharmacotherapy with examples from lipid, diabetes, and antithrombotic trials.

This review article aims to explain the important issues that data safety monitoring boards (DSMB) face when considering early termination of a trial and is specifically addressed to the needs of clinical and research cardiologists. We give an insight into the overall background and then focus on the three principal reasons for stopping trials, i.e. efficacy, futility, and harm. The statistical essentials are also addressed to familiarize clinicians with the key principles. The topic is further highlighted by numerous examples from lipid trials and antithrombotic trials. This is followed by an overview of regulatory aspects, including an insight into industry–investigator interactions. To conclude, we summarize the key elements that are the basis for a decision to stop a randomized clinical trial (RCT)

Worksite health screening programs for predicting the development of Metabolic Syndrome in middle-aged employees: a five-year follow-up study

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) management programs conventionally focus on the adults having MetS. However, risk assessment for MetS development is also important for many adults potentially at risk but do not yet fulfill MetS criteria at screening. Therefore, we conducted this follow-up study to explore whether initial screening records can be efficiently applied on the prediction of the MetS occurrence in healthy middle-aged employees.</p> <p>Methods</p> <p>Utilizing health examination data, a five-year follow-up observational study was conducted for 1384 middle-aged Taiwanese employees not fulfilling MetS criteria. Data analyzed included: gender, age, MetS components, uric acid, insulin, liver enzymes, sonographic fatty liver, hepatovirus infections and lifestyle factors. Multivariate logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence interval (CI) of risk for MetS development. The synergistic index (SI) values and their confidence intervals of risk factor combinations were calculated; and were used to estimate the interacting effects of coupling MetS components on MetS development.</p> <p>Results</p> <p>Within five years, 13% (175 out of 1384) participants fulfilled MetS criteria. The ORs for MetS development among adults initially having one or two MetS components were 2.8 and 7.3, respectively (both p < 0.01), versus the adults having zero MetS component count at screening. Central obesity carried an OR of 7.5 (p < 0.01), which far exceeded other risk factors (all ORs < 2.7). Synergistic effects on MetS development existed between coupling MetS components: 1. High blood pressure plus low-HDL demonstrated an OR of 11.7 (p < 0.01) for MetS development and an SI of 4.7 (95% CI, 2.1-10.9). 2. High blood pressure plus hyperglycemia had an OR of 7.9 (p < 0.01), and an SI of 2.7 (95% CI, 1.2-6.4).</p> <p>Conclusion</p> <p>MetS component count and combination can be used in predicting MetS development for participants potentially at risk. Worksite MetS screening programs simultaneously allow for finding out cases and for assessing risk of MetS development.</p

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the [email protected] Study

Introduction: atherosclerosis, blood vessel disease, is the main cause of cardiovascular disease associated with aging; comprising modifiable risk factors that increase because of this when it exists.Objective: to evaluate atherogenic markers and metabolic syndrome in older adults, with cardiovascular risk living in urban areas, Pinar del Río province. Methods: observational, descriptive and cross-sectional study, from the service of Clinical Laboratory at Abel Santamaría Cuadrado Teaching General Hospital  Pinar del Río with 60 years old and older patients from the urban areas, during the period 2013 - 2014. The target group included 588 patients. The sample comprised 100 patients who have at least two risk factors previously established for this study.Results: ample predominance of women (61.0 %), the risk factors of higher incidence were hypertension 67 %, and sedentary lifestyle 65 %, followed by obesity 48 %, diabetes mellitus 40 % along with smoking habit 32 %, obese with increased diameters of waist circumference 48 %, and dyslipidemia 49 %, those with high glycemic values in fasting 50 % of the sample. It was considered that 63 % of the patients studied suffer from metabolic syndrome.Conclusions: a high number of white-skin women, the predominant risk factors were hypertension followed by sedentary lifestyle, obesity, diabetes mellitus and smoking habit. Approximately half of the sample was obese with increased diameters of the waist circumference, a large part suffered from dyslipidemia and half of them showed high fasting blood glucose levels. The prevalence of metabolic syndrome was detected.IIntroducción: aterosclerosis, enfermedad de los vasos sanguíneos, principal causa de enfermedad cardiovascular vinculada al envejecimiento, con factores de riesgo modificables que se incrementan cuando esta existe.Objetivo: evaluar marcadores aterogénicos y síndrome metabólico en adultos mayores, con riesgo cardiovascular residentes en zonas urbanas de la provincia Pinar del Río.Métodos: estudio observacional, descriptivo, transversal, servicio de Laboratorio Clínico Hospital General Docente “Abel Santamaría Cuadrado” Pinar del Río, pacientes de 60 años y más de zonas urbanas, durante período 2013 - 2014. Universo de 588 pacientes. Muestra de 100 pacientes que posean mínimo de dos factores de riesgo establecidos con anterioridad para este estudio.Resultados: amplio predominio de las mujeres (61 %). Factores de riesgo de mayor incidencia hipertensión arterial 67 %, y sedentarismo 65 %, seguidos por obesidad 48 %, diabetes mellitus 40 % y hábito de fumar 32 %, obesos con diámetros aumentados de la circunferencia de la cintura 48 %, presentaban dislipidemia 49 % y tenían elevados valores de glucemia en ayunas el 50 % de la muestra. Se consideró que 63 % de los pacientes estudiados presentaron síndrome metabólico.Conclusiones: elevado número de mujeres de piel blanca, con factor de riesgo predominante de hipertensión arterial seguido por sedentarismo, obesidad, diabetes mellitus y hábito de fumar. Alrededor de la mitad de la muestra fueron obesos con diámetros aumentados de la circunferencia de la cintura, gran parte presentaban dislipidemia y la mitad altos valores de glucemia en ayunas. Se detecta prevalencia de síndrome metabólico

Influence of non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) on the pharmacodynamic activity of gliclazide in animal models

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes may occur as a result of HIV infection and/or its treatment. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. The role of Efavirenz and nevirapine on the pharmacodynamic activity of gliclazide is not currently known. The objective of this study was to examine the effect of oral administration of efavirenz and nevirapine on blood glucose and investigate their effect on the activity of gliclazide in rats (normal and diabetic) and rabbits to evaluate the safety and effectiveness of the combination.</p> <p>Methods</p> <p>Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 54 mg/kg bd. wt. of efavirenz or 18 mg/kg bd. wt. of nevirapine and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine and their combination given orally. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analysed for blood glucose by GOD/POD method.</p> <p>Results</p> <p>Efavirenz and nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 2 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h. In combination, efavirenz reduced the effect of gliclazide in rats and rabbits, and the reduction was more significant with the single dose administration of efavirenz than multiple dose administration. In combination, nevirapine has no effect on the activity of gliclazide in rats and rabbits.</p> <p>Conclusion</p> <p>Thus, it can be concluded that the combination of efavirenz and gliclazide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. The combination of nevirapine and gliclazide was safe. However, further studies are warranted.</p

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Association of Chromosome 9p21 with Subsequent Coronary Heart Disease events:A GENIUS-CHD study of individual participant data

BACKGROUND:Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS:A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103,357 Europeans with established CHD at baseline from the GENIUS-CHD Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. RESULTS:Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction Conclusions: In contrast to studies comparing individuals with CHD to disease free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development