Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

AbstractBackground:Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy.Objective:To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy.Methods:The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased.Results:A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation.Conclusion:In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5).

Variations in the Prevalence of Risk Factors for Coronary Artery Disease in Rio Grande do Sul-Brazil: A Comparative Analysis between 2002 and 2014

Abstract Background: Due to the importance of coronary artery disease (CAD), continuous investigation of the risk factors (RFs) is needed. Objective: To evaluate the prevalence of RFs for CAD in cities in Rio Grande do Sul State, and compare it with that reported in a similar study conducted in the same cities in 2002. Methods: Cross-sectional study on 1,056 healthy adults, investigating the prevalence and absolute and relative frequencies of the following RFs for CAD: obesity, systemic arterial hypertension (SAH), dyslipidemias, smoking, sedentary lifestyle, diabetes mellitus, and family history, as well as age and sex. Data was collected in 19 cities, host of the Offices of the Regional Coordinators of Health, as in the 2002 study. Results: Twenty-six percent of the sample consisted of older adults and 57% were women. The prevalence of sedentary lifestyle was 44%, history family 50%, smoking 23%, overweight/obesity 68%, dyslipidemia (high cholesterol levels) 43%, SAH 40%, and diabetes 11%. When compared to the 2002 study, the prevalence of active smoking and sedentary behavior decreased, whereas the prevalence of hypertension, dyslipidemia and obesity increased. Obesity is the most prevalent RF in women, and SAH the most prevalent in men. Conclusions: The prevalence of RFs for CAD in Rio Grande do Sul State remains high. Hypertension, obesity and dyslipidemia are still prevalent and require major prevention programs. Smoking and physical inactivity have decreased in the state, suggesting the efficacy of related campaigns.

High Blood Pressure in Adolescents of Curitiba: Prevalence and Associated Factors

Abstract Background: Arterial hypertension is a major public health problem and has increased considerably in young individuals in past years. Thus, identifying factors associated with this condition is important to guide intervention strategies in this population. Objective: To determine high blood pressure prevalence and its associated factors in adolescents. Methods: A random sample of 1,242 students enrolled in public schools of the city of Curitiba (PR) was selected. Self-administered questionnaires provided family history of hypertension, daily energy expenditure, smoking habit, daily fat intake, and socioeconomic status. Waist circumference was measured following standardized procedures, and blood pressure was measured with appropriate cuffs in 2 consecutive days to confirm high blood pressure. Relative frequency and confidence interval (95%CI) indicated high blood pressure prevalence. Bivariate and multivariate analyses assessed the association of risk factors with high blood pressure. Results: The high blood pressure prevalence was 18.2% (95%CI 15.2-21.6). Individuals whose both parents had hypertension [odds ratio (OR), 2.22; 95%CI 1.28-3.85] and those with high waist circumference (OR, 2.1; 95%CI 1.34-3.28) had higher chances to develop high blood pressure. Conclusion: Positive family history of hypertension and high waist circumference were associated with high blood pressure in adolescents. These factors are important to guide future interventions in this population.

Hypertensives' Knowledge About High-Sodium Foods and Their Behavior

Abstract Background: In Brazil, the prevalence of systemic arterial hypertension (SAH) is approximately 30% of the total population. In 2010, SAH was the cause of death of about 9.4 million people worldwide. A healthy dietary pattern is important to maintain proper blood pressure levels and, consequently, disease control. Objectives: To describe the knowledge and practices of hypertensive patients cared for at a public hypertension outpatient clinic, and its relationship with high-sodium food. Methods: We applied a questionnaire to patients with questions related to sociodemographics, dietary pattern, frequency of ingestion of certain foods, and knowledge about their own disease. Results: We studied 221 patients, 56.1% of whom were women, and 53.8% had only elementary education. Their mean age was 57.7 ±13.5 years, and 75.6% of them reported having high blood pressure, and 11.3%, diabetes mellitus. Regarding dietary pattern, 62% used ready-to-use seasonings, but 94.1% reported not adding extra salt to their ready meals. Regarding patients' knowledge about high-sodium foods and SAH, only 8 patients had 100% of right answers, 37 patients had 73.8%, and 42 patients, 57% of right answers. Conclusion: Knowledge about SAH prevention and high-sodium foods was insufficient. Based on this study's findings, more effective educational strategies targeted at this population can be developed.

Transcatheter Aortic Valve Implantation and Morbidity and Mortality-Related Factors: a 5-Year Experience in Brazil

Abstract Background: Transcatheter aortic valve implantation has become an option for high-surgical-risk patients with aortic valve disease. Objective: To evaluate the in-hospital and one-year follow-up outcomes of transcatheter aortic valve implantation. Methods: Prospective cohort study of transcatheter aortic valve implantation cases from July 2009 to February 2015. Analysis of clinical and procedural variables, correlating them with in-hospital and one-year mortality. Results: A total of 136 patients with a mean age of 83 years (80-87) underwent heart valve implantation; of these, 49% were women, 131 (96.3%) had aortic stenosis, one (0.7%) had aortic regurgitation and four (2.9%) had prosthetic valve dysfunction. NYHA functional class was III or IV in 129 cases (94.8%). The baseline orifice area was 0.67 ± 0.17 cm2 and the mean left ventricular-aortic pressure gradient was 47.3±18.2 mmHg, with an STS score of 9.3% (4.8%-22.3%). The prostheses implanted were self-expanding in 97% of cases. Perioperative mortality was 1.5%; 30-day mortality, 5.9%; in-hospital mortality, 8.1%; and one-year mortality, 15.5%. Blood transfusion (relative risk of 54; p = 0.0003) and pulmonary arterial hypertension (relative risk of 5.3; p = 0.036) were predictive of in-hospital mortality. Peak C-reactive protein (relative risk of 1.8; p = 0.013) and blood transfusion (relative risk of 8.3; p = 0.0009) were predictive of 1-year mortality. At 30 days, 97% of patients were in NYHA functional class I/II; at one year, this figure reached 96%. Conclusion: Transcatheter aortic valve implantation was performed with a high success rate and low mortality. Blood transfusion was associated with higher in-hospital and one-year mortality. Peak C-reactive protein was associated with one-year mortality.

Inhibition of the renin-angiotensin-aldosterone system: is there room for dual blockade in the cardiorenal continuum?

Antagonism of renin-angiotensin-aldosterone system is exerted through angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, renin inhibitors and mineralocorticoid receptor antagonists. These drugs have been successfully tested in numerous trials and in different clinical settings. The original indications of renin-angiotensin-aldosterone system blockers have progressively expanded from the advanced stages to the earlier stages of cardiorenal continuum. To optimize the degree of blockade of renin-angiotensin-aldosterone system, dose uptitrations of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists or the use of a dual blockade, initially identified with the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, have been proposed. The data from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study do not support this specific dual blockade approach. However, the dual blockade of angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists with direct renin inhibitors is currently under investigation while that based on an aldosterone blocker with any of the previous three drugs requires more evidence beyond heart failure. In this review, we revisited potential advantages of dual blockade of renin-angiotensin-aldosterone system in arterial hypertension and diabetes.

Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.

Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.

Polypharmacy is Associated with an Increased Risk of Bleeding in Elderly Patients with Venous Thromboembolism.

BACKGROUND: Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE: To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN: We used a prospective cohort study. PARTICIPANTS: In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES: We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS: Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS: Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.

Embolic strokes of undetermined source in the athens stroke registry: a descriptive analysis.

BACKGROUND AND PURPOSE: A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. METHODS: The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. RESULTS: Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. CONCLUSIONS: About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.

Les combinaisons fixes de medicaments antihypertenseurs. [Fixed antihypertensive drug combinations]

Arterial hypertension is a highly heterogeneous condition. It is therefore not surprising that blood pressure lowering agents acting via a given mechanism allow a normalization of blood pressure in a fraction of hypertensive subjects only. The combination of drugs with different mechanisms of action on the cardiovascular system results in a considerably higher antihypertensive efficacy, not only with regard to the absolute blood pressure reduction but also in the number of responders. This effect is not achieved at the expenses of tolerance, because usually lower doses of the combined agents are sufficient to achieve the target blood pressure. The administration of antihypertensive agents in fixed combination has the advantage of its simplicity for both the physician as well as the patient. This aspect also explains the increasing popularity of fixed combinations as a valuable option in the initial treatment of the hypertensive patient.

Bosentan and oral anticoagulants in HIV patients: what we can learn of cases reported so far.

Pulmonary arterial hypertension is an infrequent but nevertheless serious life-threatening severe complication of HIV infection. It can be treated with bosentan and oral anticoagulants. Bosentan could induce the acenocoumarol metabolism and it increases the INR values. Until now, no study of interaction between bosentan and oral anticoagulants in HIV patients has reported. So we present a case of this interaction between these drugs and we reviewed MEDLINE to identify all the papers published so far. In our case, several weeks after increasing dose of bosentan acenocoumarol dose had to be progressively increased to 70 mg/week (+33%) without obtaining an adequate INR level (2.0-3.0). Forty-nine days later, we achieved a therapeutic INR with 90 mg/week of warfarin. The use of bosentan and oral anticoagulants together in these patients require a closer monitoring during first weeks of treatment, after increasing the bosentan dose and even during longer periods of time.

Vascular dysfunction in children conceived by assisted reproductive technologies: underlying mechanisms and future implications.

Epidemiological studies in humans have demonstrated a relationship between pathological events during fetal development and increased cardiovascular risk later in life and have led to the so called "Fetal programming of cardiovascular disease hypothesis". The recent observation of generalised vascular dysfunction in young apparently healthy children conceived by assisted reproductive technologies (ART) provides a novel and potentially very important example of this hypothesis. This review summarises recent data in ART children demonstrating premature subclinical atherosclerosis in the systemic circulation and pulmonary vascular dysfunction predisposing to exaggerated hypoxia-induced pulmonary hypertension. These problems appear to be related to the ART procedure per se. Studies in ART mice demonstrating premature vascular aging and arterial hypertension further demonstrate the potential of ART to increase cardiovascular risk and have allowed to unravel epigenetic alterations of the eNOS gene as an underpinning mechanism. The roughly 25% shortening of the life span in ART mice challenged with a western style high-fat-diet demonstrates the potential importance of these alterations for the long-term outcome. Given the young age of the ART population, data on cardiovascular endpoints will not be available before 20 to 30 years from now. However, already now cohort studies of the ART population are needed to early detect cardiovascular alterations with the aim to prevent or at least optimally treat cardiovascular complications. Finally, a debate needs to be engaged on the future of ART and the consequences of its exponential growth for public health.

Association between self-reported health and sociodemographic characteristics with cardiovascular diseases in adults

OBJECTIVE To assess the association of sociodemographic and self-rated health in the presence of cardiovascular diseases and the association of this perception with the type of disease. METHODS A cross-sectional population survey study carried out with 1,232 individuals aged between 20 and 59 years of both genders living in the metropolitan region of Maringá-PR. Data were analyzed using multiple and simple logistic regression. RESULTS In multivariate analysis, the age range and self-rated health were associated with cardiovascular disease, and in the univariate analysis self-rated regular health was associated with arterial hypertension, while self-rated poor health was associated to heart failure, stroke, and to acute myocardial infarction (heart attack). CONCLUSION The differences in association of self-rated health with these diseases can indicate how individuals with certain characteristics cope with the disease, allowing for more individualized and specific health care.

Therapeutic potential of endothelin receptor modulators: lessons from human clinical trials.

The endothelin system, and in particular endothelin receptors, are targets for therapeutic intervention in human diseases. Endothelin receptor antagonists have reached clinical use for treating pulmonary arterial hypertension, and are under clinical investigation for several other diseases, such as cancer, vasospasm or fibrogenic diseases. We review the molecules that have been evaluated in the main clinical trials, from the point of view of receptor selectivity and of their chemical characteristics which were important for efficacy in pulmonary hypertension. We will also discuss future use of antagonists to endothelin receptor(s) in several human diseases and what should be the necessary properties of the future molecules for efficacy in diseases where the presently tested molecules displayed suboptimal efficacy.

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when < or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.