Lipoprotein (a): Structure, Pathophysiology and Clinical Implications

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

Malaria and Vascular Endothelium

Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease.

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

Background: End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes. Objective: To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis. Methods: Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value &#8804; 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study. Results: The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor. Conclusions: The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

Relevance to Home Blood Pressure Monitoring Protocol of Blood Pressure Measurements Taken Before First- Morning Micturition and in the Afternoon

Background: The importance of measuring blood pressure before morning micturition and in the afternoon, while working, is yet to be established in relation to the accuracy of home blood pressure monitoring (HBPM). Objective: To compare two HBPM protocols, considering 24-hour ambulatory blood pressure monitoring (wakefulness ABPM) as gold-standard and measurements taken before morning micturition (BM) and in the afternoon (AM), for the best diagnosis of systemic arterial hypertension (SAH), and their association with prognostic markers. Methods: After undergoing 24-hour wakefulness ABPM, 158 participants (84 women) were randomized for 3- or 5-day HBPM. Two variations of the 3-day protocol were considered: with measurements taken before morning micturition and in the afternoon (BM+AM); and with post-morning-micturition and evening measurements (PM+EM). All patients underwent echocardiography (for left ventricular hypertrophy - LVH) and urinary albumin measurement (for microalbuminuria - MAU). Result: Kappa statistic for the diagnosis of SAH between wakefulness-ABPM and standard 3-day HBPM, 3-day HBPM (BM+AM) and (PM+EM), and 5-day HBPM were 0.660, 0.638, 0.348 and 0.387, respectively. The values of sensitivity of (BM+AM) versus (PM+EM) were 82.6% &#215; 71%, respectively, and of specificity, 84.8% &#215; 74%, respectively. The positive and negative predictive values were 69.1% &#215; 40% and 92.2% &#215; 91.2%, respectively. The comparisons of intraclass correlations for the diagnosis of LVH and MAU between (BM+AM) and (PM+EM) were 0.782 &#215; 0.474 and 0.511 &#215; 0.276, respectively. Conclusions: The 3 day-HBPM protocol including measurements taken before morning micturition and during work in the afternoon showed the best agreement with SAH diagnosis and the best association with prognostic markers.

Biomarkers in Cardiology &#8211; Part 1 &#8211; In Heart Failure and Specific Cardiomyopathies

Cardiovascular diseases are the leading causes of mortality and morbidity in Brazil. The primary and secondary preventions of those diseases are a priority for the health system and require multiple approaches to increase their effectiveness. Biomarkers are tools used to more accurately identify high-risk individuals, to speed the diagnosis, and to aid in treatment and prognosis determination. This review aims to highlight the importance of biomarkers in clinical cardiology practice, and to raise relevant points of their use and the promises for the coming years. This document was divided into two parts, and this first one discusses the use of biomarkers in specific cardiomyopathies and heart failure.

Prevalence of Dyslipidemia According to the Nutritional Status in a Representative Sample of São Paulo

Background:Overweight is one of the major public health problems in Brazil; it is associated with dyslipidemia, which is an important risk factor for cardiovascular diseases.Objective:To evaluate the lipid profile of residents of the municipality of São Paulo, state of São Paulo, according to the nutritional status.Methods:Data from the population-based cross-sectional study ISA-Capital 2008 on a sample of residents of São Paulo were used. Participants were categorized into groups according to body mass index and age range. The levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and non-HDL cholesterol were measured. The association between lipid profile, nutricional status, and waist circumference was investigated. The data were processed using the survey mode of the Stata 11.0 software.Results:The prevalence of any type of dyslipidemia in the population was 59.74%, with low HDL-cholesterol dyslipidemia being the most common type. Not overweight individuals had higher mean levels of HDL-cholesterol and lower levels of LDL-cholesterol, total cholesterol, triglycerides, and non-HDL cholesterol when compared with the overweight group. The rate of inadequacy of these variables was higher in the overweight individuals, regardless of the age group, to the exception of LDL-cholesterol in the adults and elderly. A higher prevalence of isolated hypertriglyceridemia was observed in individuals with higher waist circumference among the adults and the total population.Conclusion:The results indicate an association between dyslipidemia and overweight in the population of the city of São Paulo. The most prevalent dyslipidemia in this population was low HDL-cholesterol.

Improving Post-Discharge Medication Adherence in Patients with CVD: A Pilot Randomized Trial

Background:Effective interventions to improve medication adherence are usually complex and expensive.Objective:To assess the impact of a low-cost intervention designed to improve medication adherence and clinical outcomes in post-discharge patients with CVD.Method:A pilot RCT was conducted at a teaching hospital. Intervention was based on the four-item Morisky Medication Adherence Scale (MMAS-4). The primary outcome measure was medication adherence assessed using the eight-item MMAS at baseline, at 1 month post hospital discharge and re-assessed 1 year after hospital discharge. Other outcomes included readmission and mortality rates.Results:61 patients were randomized to intervention (n = 30) and control (n = 31) groups. The mean age of the patients was 61 years (SD 12.73), 52.5% were males, and 57.4% were married or living with a partner. Mean number of prescribed medications per patient was 4.5 (SD 3.3). Medication adherence was correlated to intervention (p = 0.04) and after 1 month, 48.4% of patients in the control group and 83.3% in the intervention group were considered adherent. However, this difference decreased after 1 year, when adherence was 34.8% and 60.9%, respectively. Readmission and mortality rates were related to low adherence in both groups.Conclusion:The intervention based on a validated patient self-report instrument for assessing adherence is a potentially effective method to improve adherent behavior and can be successfully used as a tool to guide adherence counseling in the clinical visit. However, a larger study is required to assess the real impact of intervention on these outcomes.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

Background:Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial.Objective:To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective.Methods:We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied.Results:Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios.Conclusions:Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation

Background: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. Objective: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). Methods: To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Results: Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = &#8722;0.21; p < 0.001), even after adjustments for age and sex (beta coefficient &#8722;94.8; p = 0.001). The relative risk for a positive D-dimer value attributed to hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040). The correlation remained statistically significant in patients free from antihypertensive drugs (r = &#8722;0.25; p = 0.018), but not in those taking angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics. Conclusions: The inverse correlation between values of potassium and D-dimer in patients with AAF provides important and complementary information about the thromboembolic risk of these patients.

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)