Walter Masson

Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder

BackgroundThere is a high prevalence of depression in individuals with type 2 diabetes mellitus. Depressive disorders are associated with increased medical morbidity and mortality in individuals with diabetes. It has been demonstrated that there is a higher prevalence of diabetic complications among individuals with diabetes and depression compared to those without depression. Several biological alterations have been reported in individuals with depressive disorders, particularly abnormal levels of endocrine-inflammatory markers.This study aims to determine the prevalence of major depressive disorder (MDD) in type 2 diabetes patients, the prevalence of cardiovascular events in individuals with and without MDD and to compare the endocrine-inflammatory profile between groups.MethodsThe study was approved by the “Comité de Etica de Protocolos de Investigación del Departamento de Docencia e Investigación del Hospital Italiano de Buenos Aires” with the number “1262” and included only patients who provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Habeas Data law on protection of personal data (Law Nª 25326, Argentina).Type 2 diabetes patients (n = 61) were included and they were classified as having MDD or not according to DSM-IV. Macrovascular disease was obtained from the medical history. Additionally, the intima-media thickness of the common carotid, carotid bifurcations and internal carotid arteries was measured non-invasively by two-dimensional ultrasound imaging. Fasting glucose, fasting lipid profile, inflammatory (CRP, TNF-α) and endocrine (urine free cortisol and saliva cortisol) markers. Student t tests were used to compare means for normally distributed variables and Mann-Whitney test for variables without normal distribution. Relative frequencies were calculated and a chi-square analysis was conducted. Data were expressed as mean ± standard deviation (SD) or median and interquartile range. Multivariable logistic regression was used to determine the relative odds of clinical cardiovascular disease in individuals with compared to those without depression. Differences were considered significant using a two-sided p < 0.05.Results21 patients (34%) had MDD and 40 patients (66%) didn’t have MDD. Diabetic patients with MDD had significantly higher CRP levels (4.1(1.9-7.6) vs 1.5(0.5-4.4) mg/l; p = 0.02) and 24-hour urine free cortisol (71.4 ± 21.3 vs 59.8 ± 29.3 ug/24 h; p = 0.03). The other metabolic and inflammatory parameters were not statistically different between groups. There was a significantly higher prevalence of cardiovascular events in individuals with MDD: 38% for the depressive group vs 15% for non-depressive group, p = 0.04). Patients with MDD had a 3.5-fold greater odd of having cardiovascular disease.ConclusionsDiabetic patients with depression are more likely to have cardiovascular events, and different factors can determine this high association.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression

Background Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers. Objective To assess the association between changes in lipid markers and regression of CPV using published data. Methods We collected data from the control, placebo and intervention arms in studies that compared the effect of lipidlowering treatments on CPV, and from the placebo and control arms in studies that tested drugs that did not affect lipids. Baseline and final measurements of plaque volume, expressed in mm3, were extracted and the percentage changes after the interventions were calculated. Performing three linear regression analyses, we assessed the relationship between percentage and absolute changes in lipid markers and percentage variations in CPV. Results Twenty-seven studies were selected. Correlations between percentage changes in LDL-C, non-HDL-C, and apolipoprotein B (ApoB) and percentage changes in CPV were moderate (r = 0.48, r = 0.47, and r = 0.44, respectively). Correlations between absolute differences in LDL-C, non‑HDL-C, and ApoB with percentage differences in CPV were stronger (r = 0.57, r = 0.52, and r = 0.79). The linear regression model showed a statistically significant association between a reduction in lipid markers and regression of plaque volume. Conclusion A significant association between changes in different atherogenic particles and regression of CPV was observed. The absolute reduction in ApoB showed the strongest correlation with coronary plaque regression.

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol

Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define “lipid discordance” if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

Cardiovascular Risk Stratification in Patients with Metabolic Syndrome Without Diabetes or Cardiovascular Disease: Usefulness of Metabolic Syndrome Severity Score

IntroductionThe estimated cardiovascular risk determined by the different risk scores, could be heterogeneous in patients with metabolic syndrome without diabetes or vascular disease. This risk stratification could be improved by detecting subclinical carotid atheromatosis.AimsTo estimate the cardiovascular risk measured by different scores in patients with metabolic syndrome and analyze its association with the presence of carotid plaque.MethodsNon-diabetic patients with metabolic syndrome (Adult Treatment Panel III definition) without cardiovascular disease were enrolled. The Framingham score, the Reynolds score, the new score proposed by the 2013 ACC/AHA Guidelines and the Metabolic Syndrome Severity Calculator were calculated. Prevalence of carotid plaque was determined by ultrasound examination. A Receiver Operating Characteristic analysis was performed.ResultsA total of 238 patients were enrolled. Most patients were stratified as “low risk” by Framingham score (64%) and Reynolds score (70.1%). Using the 2013 ACC/AHA score, 45.3% of the population had a risk ≥7.5%. A significant correlation was found between classic scores but the agreement (concordance) was moderate. The correlation between classical scores and the Metabolic Syndrome Severity Calculator was poor. Overall, the prevalence of carotid plaque was 28.2%. The continuous metabolic syndrome score used in our study showed a good predictive power to detect carotid plaque (area under the curve 0.752).ConclusionIn this population, the calculated cardiovascular risk was heterogenic. The prevalence of carotid plaque was high. The Metabolic Syndrome Severity Calculator showed a good predictive power to detect carotid plaque.

Estimation of cardiovascular risk and detection of subclinical carotid atheromatosis in patients with diabetes without a history of cardiovascular disease

Objectives Cardiovascular risk estimated by several scores in patients with diabetes mellitus without a cardiovascular disease history and the association with carotid atherosclerotic plaque (CAP) were the aims of this study. Materials and methods Cardiovascular risk was calculate using United Kingdom Prospective Diabetes Study (UKPDS) risk engine, Framingham risk score for cardiovascular (FSCV) and coronary disease (FSCD), and the new score (NS) proposed by the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol. Ultrasound was used to assess CAP occurrence. A receiver operating characteristic (ROC) analysis was performed. Results One hundred seventy patients (mean age 61.4 ± 11 years, 58.8% men) were included. Average FSCV, FSCD and NS values were 33.6% ± 21%, 20.6% ± 12% and 24.8% ± 18%, respectively. According to the UKPDS score, average risk of coronary disease and stroke were 22.1% ± 16% and 14.3% ± 19% respectively. Comparing the risks estimated by the different scores a significant correlation was found. The prevalence of CAP was 51%, in patients with the higher scores this prevalence was increased. ROC analysis showed a good discrimination power between subjects with or without CAP. Conclusion The cardiovascular risk estimated was high but heterogenic. The prevalence of CAP increased according to the strata of risk. Understanding the relationship between CAP and scores could improve the risk estimation in subjects with diabetes.

The new guidelines of high blood pressure substantially increase prevalence of hypertension in Argentina

Hypertension occupies the first place for global disease burden and all-cause mortality.1 Moreover, the evidence favoring antihypertensive drug therapy to reduce cardiovascular events and mortality is conclusive.2 In Argentina, the Third National Risk Factor Survey determined that 34.1% of the population received the diagnosis of high blood pressure.3 By the end of 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) published the new guideline for the detection, prevention, management and treatment of high blood pressure.4 This guideline is an update of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7). Compared with the JNC7 guideline, the 2017 ACC/AHA guideline recommends the use of lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) values to define hypertension. On the other hand, these new recommendations suggest taking into account the cardiovascular risk estimated with the new score for cardiovascular disease used by the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to determine which patients with stage 1 hypertension should receive antihypertensive drugs.5 As a consequence, the number of patients diagnosed with hypertension would increase considerably and many patients should be treated with antihypertensive drugs. The objectives of this study were: 1) to determine what proportion of non-hypertensive patients according to the previous recommendations in primary prevention were diagnosed as hypertensive by the 2017 ACC/AHA guideline; 2) to establish how many patients should receive pharmacological treatment after applying the new recommendations; 3) To determine reasons to justify the indication of antihypertensive therapy.

Discordancia lipídica y placa carotídea en pacientes obesos en prevención primaria

INTRODUCTION Obese patients with lipid discordance (non-HDL cholesterol levels 30mg/dL above the LDL-c value) may have a greater prevalence of carotid atherosclerotic plaque (CAP). Our study objectives were: 1) To assess the prevalence of lipid discordance in a primary prevention population of obese patients; 2) To investigate the association between lipid discordance and presence of CAP. METHODS Obese subjects aged >18 years (BMI ≥30kg/m2) with no cardiovascular disease, diabetes, or lipid-lowering treatment from six cardiology centers were included. Lipid discordance was defined when, regardless of the LDL-c level, the non-HDL cholesterol value exceeded the LDL-c value by 30mg/dL. Presence of CAP was identified by ultrasonography. Univariate and multivariate analyses were performed to explore the association between lipid discordance and presence of CAP. RESULTS The study simple consisted of 325 obese patients (57.2% men; mean age, 52.3 years). Prevalence of lipid discordance was 57.9%. CAP was found in 38.6% of patients, but the proportion was higher in subjects with lipid discordance as compared to those without this lipid pattern (44.4% vs. 30.7%, P=.01). In both the univariate (OR: 1.80; 95% CI: 1.14-2.87; P=.01) and the multivariate analysis (OR: 2.07; 95% CI: 1.22-3.54; P=.007), presence of lipid discordance was associated to an increased probability of CAP. CONCLUSION In these obese patients, lipid discordance was associated to greater prevalence of CAP. Evaluation of obese patients with this strategy could help identify subjects with higher residual cardiovascular risk.

Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk

BACKGROUND Cholesteryl ester transfer protein (CETP) inhibitors are a class of drugs that targets the CETP enzyme to significantly increase serum high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels. As HDL-C has potential antidiabetic properties, and the beneficial effects of CETP drugs on glucose homoeostasis have not been sufficiently studied, the aims of this study were: (1) to evaluate the effect of CETP inhibitors on the incidence of diabetes; and (2) to assess the association between CETP inhibitor-induced changes in HDL-C levels and incidence of diabetes. METHODS A meta-analysis was performed of randomized controlled clinical trials of CETP inhibitor therapy, either alone or combined with other lipid-lowering drugs, reporting data from new cases of diabetes with a minimum of 6 months of follow-up, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A fixed-effects meta-regression model was then applied. RESULTS Four eligible trials of CETP inhibitors, involving a total of 73,479 patients, were considered for the analyses, including 960 newly diagnosed cases of diabetes in the CTEP inhibitor group vs 1086 in the placebo group. CETP inhibitor therapy was associated with a significant 12% reduction in incidence of diabetes (OR: 0.88, 95% CI: 0.81-0.96; P=0.005). Assessment of the relationship between on-treatment HDL-C and the effect of CETP inhibitors showed a statistically non-significant trend (Z=-1.13, P=0.26). CONCLUSION CETP inhibitors reduced the incidence of diabetes. The improvement in glucose metabolism may have been related, at least in part, to the increase in HDL-C concentration.

Role of Niacin in Cardiovascular Prevention: The Debate Continues

We read with great interest the meta-analysis of niacin published by Garg et al. The authors concluded that niacin therapy does not lead to significant reductions in mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease. In contrast with this conclusion, we have recently published a meta-analysis that included 35,723 subjects in which we demonstrated that niacin significantly reduces cardiovascular events. In addition, we also found significant associations between the amount of on-treatment cholesterol and triglyceride differences between the trial arms and the natural log-adjusted odds ratio for any cardiovascular event after performing random-effects, metaregression analyses. In line with the conclusion of Garg et al, we also reported the absence of a significant association between the differences in high-density lipoprotein cholesterol and the incidence of cardiovascular events. These findings led us to postulate that niacin benefits seem to be mediated by the reduction in atherogenic particles. Of interest, both meta-analyses agreed in the futility of niacin in stroke prevention; however, their clinical conclusions are discordant. How can we explain these different results? We did not evaluate all-cause mortality; however, cardiac death was included in 2 combined end points (any cardiovascular event and major coronary events), outcomes that were selected in previous meta-analyses. We consider that Garg et al’s affirmation on the lack of effect of niacin on preventing recurrent cardiovascular events is too dogmatic, considering that the only nonfatal end point evaluated was myocardial infarction. In fact, our meta-analysis showed that niacin treatment was associated with a 41% reduction in any revascularization,

Asociación entre la razón triglicéridos/colesterol HDL y ateromatosis carotídea en mujeres posmenopáusicas de mediana edad

BACKGROUND AND OBJECTIVE The triglyceride/HDL cholesterol ratio, as a surrogate marker of insulin resistance, may be associated to presence of subclinical carotid atherosclerosis in postmenopausal women. The aim of this study was to explore this association. PATIENTS AND METHODS Women (last menstrual period≥2 years) in primary prevention up to 65 years of age were recruited. Association between the triglyceride/HDL cholesterol (HDL-C) ratio and presence of carotid plaque, assessed by ultrasonography, was analyzed. ROC analysis was performed, determining the precision of this ratio to detect carotid plaque. RESULTS A total of 332 women (age 57±5 years) were recruited. Triglyceride/HDL-C ratio was 2.35±1.6. Prevalence of carotid plaque was 29%. Women with carotid plaque had higher triglyceride/HDL-C ratios (3.33±1.96 vs. 2.1±1.2, P<.001) than women with no carotid plaque. A positive relationship was seen between quintiles of this ratio and prevalence of carotid plaque (p<.001). Regardless of other risk factors, women with higher triglyceride/HDL-C ratios were more likely to have carotid plaque (odds ratio 1.47, 95% confidence interval 1.20-1.79, P<.001). The area under the curve of the triglyceride/HDL-C ratio to detect carotid plaque was .71 (95% confidence interval .65 to .76), and the optimal cut-off point was 2.04. CONCLUSIONS In postmenopausal women in primary prevention, insulin resistance, estimated from the triglyceride/HDL-C ratio, was independently associated to a greater probability of carotid plaque. A value of such ratio greater than 2 may be used for assessing cardiovascular risk in this particular group of women.