Temas de actualidad en cardiología: riesgo vascular y rehabilitación cardiaca

Cardiovascular disease develops in a slow and subclinical manner over decades, only to manifest suddenly and unexpectedly. The role of prevention is crucial, both before and after clinical appearance, and there is ample evidence of the effectiveness and usefulness of the early detection of at-risk individuals and lifestyle modifications or pharmacological approaches. However, these approaches require time, perseverance, and continuous development. The present article reviews the developments in 2013 in epidemiological aspects related to prevention, includes relevant contributions in areas such as diet, weight control methods (obesity is now considered a disease), and physical activity recommendations (with warnings about the risk of strenuous exercise), deals with habit-related psychosocial factors such as smoking, provides an update on emerging issues such as genetics, addresses the links between cardiovascular disease and other pathologies such as kidney disease, summarizes the contributions of new, updated guidelines (3 of which have recently been released on topics of considerable clinical importance: hypertension, diabetes mellitus, and chronic kidney disease), analyzes the pharmacological advances (largely mediocre except for promising lipid-related results), and finishes by outlining developments in the oft-neglected field of cardiac rehabilitation. This article provides a briefing on controversial issues, presents interesting and somewhat surprising developments, updates established knowledge with undoubted application in clinical practice, and sheds light on potential future contributions.     

Impacto da frequência posológica na adesão terapêutica em doenças cardiovasculares crónicas: revisão sistemática e meta‐análise

Introduction and ObjectiveNon‐adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non‐adherence. The complexity of dosing regimens is one of the factors identified as contributing to non‐adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease.MethodsMEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once‐daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow‐up were included. The results of the studies were pooled through a random effects meta‐analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I² test.ResultsFour RCTs (a total of 2557 patients) were included. Dosing regimens with once‐daily administration were associated with a significant 56% reduction in risk of non‐adherence to drug therapy (RR: 0.44; 95% CI: 0.35‐0.54, I²=25%).ConclusionsFew clinical trials have assessed the long‐term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non‐adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established.     

Ceramides are associated with inflammatory processes in human mediastinal adipose tissue

Background and AimCeramides are poorly characterized in human adipose tissue. The aim of this study was to investigate concentrations of different ceramide species in human subcutaneous and visceral adipose tissue depots and to determine associations between ceramides and global gene expression profiles.Methods and ResultsConcentrations of six ceramide species were determined in plasma and in subcutaneous and mediastinal adipose tissue from 10 overweight subjects (BMI 29.4 ± 4.9 kg/m²). In the adipose tissue biopsies gene expression arrays were performed and relationships between ceramides and gene expression analyzed. Immunostaining of the two adipose tissue depots was performed in an independent group of 10 patients. Mediastinal adipose tissue contained significantly higher concentrations (p < 0.05) of all six ceramide species than the subcutaneous depot. Of the six ceramides in plasma, concentrations of only two (Cer d18:1/18:0 and Cer d18:1/22:0) correlated significantly (p < 0.05) with the corresponding species in mediastinal adipose tissue, but there were no significant correlations between ceramides in plasma and subcutaneous adipose tissue. Multivariate analysis identified significant correlations between the total ceramide concentration and global gene expression within mediastinal, but not subcutaneous adipose tissue, according to cross-validation. Gene ontology analysis of genes related to ceramides in the mediastinal depot revealed that genes positively correlated with ceramides were associated mainly with immune and inflammatory categories, while genes negatively correlated with ceramides were associated mainly with lipid and carbohydrate metabolism.ConclusionsCeramides in human mediastinal adipose tissue may be involved in inflammation and lipid and carbohydrate metabolism.     

Increased atherosclerosis in mice with increased vascular biglycan content

Objective

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development.

Methods

Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4–12 weeks.

Results

LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content.

Conclusion

Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development.     

Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized.     

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins

Objective

The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins.

Methods

Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers.

Results

Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼−25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2.

Conclusion

Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.     

Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

Objective

Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.

Materials and Methods

We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.

Results

During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).

Conclusions

Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.     

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters,cardiometabolic risk factors and glycemic control in childhood obesity

Objective

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The aim of this study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in childhood obesity.

Materials and Methods

142 overweight/obese (BMI > 90th percentile) candidates (7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and biochemical parameters were obtained at beginning and completion. An oral glucose tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program.

Results

The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Conclusions

The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation.     

Effect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome

Objective

Metabolic syndrome (MetS) is associated with cardiovascular disease (CVD). Insulin resistance has been hypothesized as the underlying feature of MetS. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are widely used antihypertensives that may improve insulin sensitivity. The aim of the study is to evaluate the effect of ACEI/ARB on incident CVD events in older hypertensive patients with MetS.

Materials/Methods

We used the Cardiovascular Health Study, a prospective cohort study of individuals > 65 years of age to evaluate ACEI/ARB use and time to CVD events (including coronary and cerebrovascular events). The study included 777 subjects who had hypertension and ATP III-defined MetS, but free of CVD and diabetes at baseline. Cox regression models were used to evaluate the effect of ACEI/ARB as compared to other antihypertensives on the time to the first CVD events.

Results

ACEI/ARB use was associated with a decreased risk of CVD events (adjusted HR = 0.658, 95 % C.I. [0.436–0.993]) compared to other antihypertensives. When CVD endpoints were evaluated separately, use of ACEI/ARB was associated with lower rates of angioplasty and coronary events (HR of 0.129 and 0.530 respectively, with 95 % CI [0.017–0.952] and [0.321–0.875]).

Conclusions

ACEI/ARB use was associated with a lower risk of CVD events in older hypertensive patients with MetS, primarily due to a reduction in coronary events. The potential protective effect of ACEI/ARB on CVD events in older individuals with MetS will need further confirmation from prospective studies.     

Effects of dehydroepiandrosterone (DHEA) supplementation on the lipid profile: A systematic review and dose-response meta-analysis of randomized controlled trials

Background and aimsDehydroepiandrosterone (DHEA) supplementation has gained attention in individuals with adrenal insufficiency, and as a tool for increasing androgens and estrogens whereby is proposed to improve the accretion of muscle and bone mass. However, DHEA supplementation has demonstrated negative effects on the lipid profile and, thus, we aimed to analyze the body of evidence in this regard.Methods and resultsA systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) was performed employing in Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar, then including relevant articles that addressed the effects of DHEA supplementation on the lipid profile, up to February 2020. Combined findings were generated from 23 eligible articles. Hence, total cholesterol (TC) (weighted mean difference (WMD): −3.5 mg/dl, 95% confidence interval (CI): −8.5 to 1.6)), low-density lipoprotein-cholesterol (LDL-C) (WMD: 0.34 mg/dl, 95% CI: −3 to 3.7) and triglycerides (TG) levels (WMD: −2.85 mg/dl, 95% CI: −9.3 to 3.6) did not alter in DHEA group compared to the control, but HDL-C levels significantly reduced in DHEA group (WMD: −3.1 mg/dl, 95% CI: −4.9 to −1.3). In addition, a significant reduction in HDL-C values was observed in studies comprising women (WMD: −5.1 mg/dl, 95% CI: −7.2 to −3) but not in males (WMD: 0.13 mg/dl, 95% CI: −1.4 to 1.7).ConclusionsOverall, supplementation with DHEA did not change circulating values of TC, LDL-C and TG, whereas it may decrease HDL-C levels. Further long-term RCTs are required to investigate the effects of DHEA particularly on major adverse cardiac events.