Do antihypertensive drugs combinations in single-pill combination improve cardiovascular outcomes? / ¿Las combinaciones de medicamentos antihipertensivos en un solo comprimido mejoran los resultados cardiovasculares?

Abstract Recommendations and guidelines propose to com bine antihypertensive drugs to improve BP control, highlighting the advantages of single-pill combinations (SPCs) to improve treatment adherence. It is speculated that, compared with free-dose combinations (Free-DCs), SPC should achieve a reduction in cardiovascular (CV) events and mortality through better adherence and BP control. However, there is little information in this regard. For this reason, the objective of this review was to provide a descriptive analysis the differences in CV outcomes between SPCs antihypertensive drugs treat ments vs. Free-DCs treatments. Ten studies were found and none had a randomized controlled design. Medi cation adherence was higher with SPCs, but outcomes were not adjusted for the adherence/persistence. When groups were compared according to similar adherence degrees, the statistical significance in favor of SPCs disappeared. Thus, randomized controlled studies are necessary to evaluate if SPCs have any effect beyond the improvement of the adherence to hypertensive treatment.

Resumen Las recomendaciones y las guías proponen combinar fármacos antihipertensivos para mejorar el control de la presión arterial, destacando las ventajas de las combi naciones en un solo comprimido para mejorar la adhe rencia al tratamiento. Se especula que, en comparación con las combinaciones en varios comprimidos, deberían lograr una reducción de los eventos cardiovasculares y de la mortalidad a través de una mejor adherencia y con trol de la presión. Sin embargo, hay poca información al respecto. Por esta razón, el objetivo de esta revisión fue proporcionar un análisis descriptivo de las diferencias en los resultados cardiovasculares y la mortalidad entre los tratamientos con combinaciones de antihipertensi vos en un solo comprimido vs. combinaciones de los mismos grupos de fármacos en varios comprimidos. Se encontraron diez estudios, pero ninguno tenía un dise ño controlado aleatorio. La adherencia a la medicación fue mayor con las combinaciones en un comprimido, pero los resultados no se ajustaron por la adherencia/ persistencia. Cuando se compararon los grupos según grados de adherencia similares, la significación estadís tica a favor de las combinaciones en un comprimido se perdió. Por lo tanto, son necesarios estudios controlados aleatorios para evaluar si las combinaciones de antihi pertensivos en un comprimido tienen algún efecto más allá de la mejora de la adherencia al tratamiento.

Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis

Aims: This study aims to assess differences in severity of short-term (<1 year) and long-term (_x005F_x0001_1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients. Methods: A systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulintreated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I2 statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias. Results: A total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR ¼ 1.75 [1.24,2.47]; p ¼ 0.002), MI (RR ¼ 1.81[1.14,2.87]; p ¼ 0.01], stent thrombosis (RR ¼ 1.63[1.13, 2.35]; p ¼ 0.009) and target lesion revascularization (TLR) (RR ¼ 1.29[1.02,1.63]; p ¼ 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR ¼ 1.55 [1.22, 1.97]; p ¼ 0.0003), MI (RR ¼ 1.63 [1.35, 1.97]; p¼<0.00001), MACE (R ¼ 1.47 [1.31, 1.65]; p¼<0.00001), stent thrombosis (RR ¼ 1.54 [1.19,1.99]; p ¼ 0.001), TLR (RR ¼ 1.40 [1.18, 1.66]; p ¼ 0.0001), target vessel revascularization (TVR) (RR ¼ 1.35 [1.11, 1.64]; p ¼ 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients. Conclusion: Despite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.

El papel del riñón en la homeostasis de la glucosa y drogas de acción renal en el tratamiento de la diabetes mellitus tipo 2 / Kidney role in the glucose's homeostasis and drugs of renal action in the treatment of type 2 diabetes mellitus

Los riñones contribuyen a la homeostasis de la glucosa a través de varios mecanismos, incluyendo la gluconeogénesis, utilización y reabsorción de la glucosa a partir del filtrado glomerular. Bajo condiciones fisiológicas normales, la glucosa filtrada es casi totalmente reabsorbida en el epitelio de las células tubulares; en consecuencia, no aparece glucosa en la orina. El transporte de glucosa dentro de las células epiteliales del túbulo se cumple gracias a cotransportadores activos glucosa-sodio (SGLT), una familia de proteínas dependientes de adenosin trifosfato (ATP) involucradas en el transporte de glucosa contra un gradiente de concentración con carga simultánea de sodio, igualmente en contra gradiente. La mayoría de la glucosa filtrada es reabsorbida por medio del SGLT2, un transportador de baja afinidad pero elevada capacidad localizado, predominantemente, en el segmento S1 del tubo contorneado proximal. Por largo tiempo la inhibición del SGLT2 ha sido considerada como un abordaje terapéutico potencial de la hiperglucemia en la diabetes mellitus tipo 2 (DM2), ya que al prevenir la reabsorción de glucosa por los túbulos renales promueven su excreción renal y descienden los valores de la glucemia. Los datos en humanos indican que los inhibidores de SGLT2 representan una estrategia novedosa y efectiva para controlar las cifras de glucemia en los pacientes con DM2. El recién publicado estudio EMPA-REG OUTCOME diseñado para examinar los desenlaces cardiovasculares con empagliflozina en sujetos con DM2 y enfermedad ardiovascular coexistente mostró beneficios tempranos, los cuales se mantuvieron durante el período de observación(AU)

The kidneys contribute to glucose homeostasis through several mechanisms, including gluconeogenesis, glucose use, and glucose reabsorption from the glomerular filtrate. Under normal physiological conditions, this filtered glucose is almost completely reabsorbed by renal tubular epithelial cells; thus, there is no glucose in urine. The transport of glucose into renal tubular epithelial cells is mediated by active cotransporters, the SGLT, a family of ATP-dependent proteins involved in the transport of glucose against a concentration gradient with simultaneous transport of Na+ down a concentration gradient. Most of the filtered glucose is reabsorbed through SGLT2, a low-affinity high-capacity transporter located predominantly in the S1 segment of the renal proximal tubule. Inhibition of SGLT2 has long been regarded as a potential treatment approach for hyperglycemia during T2DM, as they prevent glucose reabsorption from renal tubules, thereby promoting urinary glucose excretion and decreasing plasma glucose levels. Current data in humans indicate that SGLT2 inhibitors represent an effective and novel strategy to control the plasma glucose concentration in patients with T2DM. The recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease showed that the benefits were noted early and continued throughout the study(AU)

Plasma renin activity and risk of cardiovascular and mortality outcomes among individuals with elevated and nonelevated blood pressure

BACKGROUND: We sought to evaluate plasma renin activity (PRA) levels and risk of mortality and cardiovascular events among individuals with elevated blood pressure [systolic blood pressure (SBP) ≥ 140 mmHg] and those with controlled blood pressure (SBP < 140 mmHg) in a large diverse population. METHODS: A retrospective cohort study between January 1, 2007, and December 31, 2013, among adults (≥ 18 years) within an integrated health system was conducted. Subjects were categorized by SBP into 2 groups: SBP < 140 mmHg and SBP ≥ 140 mmHg and then further categorized into population-based PRA tertiles within each SBP group. Cox proportional hazard modeling was used to estimate hazard ratios for cardiovascular and mortality outcomes among tertiles of PRA levels. RESULTS: Among 6,331 subjects, 32.6% had SBP ≥ 140 mmHg. Multivariable hazard ratios and 95% confidence interval for PRA tertiles T2 and T3 compared to T1 in subjects with SBP ≥ 140 mmHg were 1.42 (0.99–2.03) and 1.61 (1.12–2.33) for ischemic heart events; 1.40 (0.93–2.10) and 2.23 (1.53–3.27) for congestive heart failure; 1.10 (0.73–1.68) and 1.06 (0.68–1.66) for cerebrovascular accident; 1.23 (0.94–1.59) and 1.43 (1.10–1.86) for combined cardiovascular events; and 1.39 (0.97–1.99) and 1.35 (0.92–1.97) for all-cause mortality, respectively. Among the SBP < 140 mmHg group, there was no relationship between PRA levels and outcomes. CONCLUSION: Higher PRA levels demonstrated increased risk for ischemic heart events and congestive heart failure and a trend toward higher mortality among individuals with SBP ≥ 140 mmHg but not among those with SBP < 140 mmHg.

Surgical Treatment of Obesity and Diabetes.

Surgery for obesity is the last option but it is the most effective. Resolution of comorbid diseases with obesity occurs depending upon the amount of weight loss, age of the patients, duration of comorbid disorders. After malabsorptive surgeries, patient has to be on life-long vitamin supplements. Various types of surgeries done in morbid obesity with their merits and demerits have been described in this review.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease / Considerações sobre o significado clínico-funcional da disfunção autonômica cardíaca na doença de Chagas

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

INTRODUÇÃO: Lesões isoladas ou combinadas de várias estruturas do sistema nervoso autônomo ocorrem nas formas crônicas da doença de Chagas. Na forma indeterminada, as lesões são discretas e podem estar até ausentes, enquanto nas formas cardíaca e digestória exclusivas ou combinadas elas são comumente mais pronunciadas. Na dependência da sua maior ou menor severidade, estas lesões podem resultar em variáveis graus de disfunção parassimpática e/ou simpática, principalmente a primeira. Apesar da crítica influência autonômica sobre o funcionamento cardiovascular, o significado fisiopatológico e clínico, notadamente em longo prazo, da disfunção autonômica cardíaca permanece desconhecido na doença de Chagas. MÉTODOS: Revisão sobre a disfunção autonômica cardíaca na doença de Chagas e suas potenciais consequências, como base para considerações acerca da possível relação entre este distúrbio e desfechos clínicos e funcionais globais e cardiovasculares desfavoráveis. RESULTADOS: Os potenciais desfechos que a disautonomia cardíaca pode variavelmente determinar ou predispor na doença de Chagas incluem: arritmias transitórias ou sustentadas, morte súbita, mal prognóstico global e cardiovascular, morbi-mortalidade aumentada, deficiente adaptação cardiovascular a demandas funcionais e/ou em resposta a estímulos internos e externos por meio de ajustes da frequência cardíaca e outras variáveis hemodinâmicas, e distúrbios imunomoduladores e psico-funcionais. CONCLUSÕES: A alteração da modulação autonômica cardíaca na doença de Chagas pode não representar mero epifenômeno sem significado. Evidências indiretas sugerem papel importante desta alteração como fator predisponente ou determinante primário para o desenvolvimento secundário de distúrbios funcionais manifestos ou não e consequências clínicas cardiovasculares, e para a ocorrência de desfechos desfavoráveis.

The Impact of the Aortic Pulse Wave Velocity on the Cardiovascular Outcomes of Hemodialysis Patients

The aims of our study were to identify the risk factors for an increased aortic pulse wave velocity (AoPWV) and to assess the impact of the AoPWV on the cerebro-cardiovascular (CV) outcomes of hemodialysis (HD) patients. Seventy two HD patients were included, and the AoPWV, the echocardiography and the biochemical parameters were measured. After dividing the patients into tertiles according to the AoPWV values, we defined the low, the middle and the high AoPWV groups. The patients in the high AoPWV group showed a significantly higher age and high-sensitivity C-reactive protein level, a greater prevalence of diabetes and statin use, left ventricular hypertrophy, average pulse pressure (PP), AoPWV and left ventricular mass index and a lower serum albumin level than those in the low AoPWV group (p<0.05). On multivariate regression analysis of the AoPWV, age and the average PP were independently related to the AoPWV (p<0.05). On the multivariate Cox analysis for CV outcomes, the AoPWV and the average PP remained significant independent predictors of CV events. Our data suggest that an increased AoPWV is an independent predictor for the CV outcomes of HD patients.