Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

Muscle strength is associated with lower diastolic blood pressure in schoolchildren.

Cardiorespiratory fitness (CRF) provides protection against the elevated blood pressure in overweight youth. Less is known regarding any similar protective effect of muscular fitness. We investigated how handgrip strength, an easy to implement measure of muscular strength, interacted with CRF and BMI to determine blood pressure in youth. We measured systolic (SBP) and diastolic (DBP) blood pressure, handgrip strength (HG), CRF and body mass index (BMI) in n=7329 10-16year-olds (47% girls). We defined elevated blood pressure as >91st percentile and Good HG as >33rd percentile. Participants were classified as Fit or Unfit and as Normal or Overweight/Obese based on international standards. The prevalence of elevated SBP was 23%, and 44% of participants had elevated DBP. In unfit participants Good HG was associated with lower SBP (z=0.41 (95%CI: 0.20-0.61) and DBP (z=0.29 (95%CI: 0.12-0.47). In Overweight/Obese participants, DBP was z=0.24 (95%CI: 0.14-0.34) lower in the Good (versus Low) HG group. Overweight/Obese participants with Good HG also had a 32% lower risk of elevated DBP (OR: 0.68, 95%CI: 0.57-0.82). This association was attenuated but remained important after adjusting for BMI (20% risk reduction, OR: 0.80, 95%CI: 0.63-1.01). Muscular fitness appears to play some protective role against the risk of elevated blood pressure; particularly for the more prevalent measure: elevated DBP (44%). Effects may be restricted to Overweight / Obese or unfit youth, who have an increased risk of elevated BP and also may be less likely to engage in traditional cardiorespiratory fitness training. Research to determine the effects of muscular fitness training on blood pressure is warranted in these subgroups.

Psychosocial factors and obesity in 17 high-, middle- and low-income countries: the Prospective Urban Rural Epidemiologic study.

BACKGROUND/OBJECTIVES: Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or central obesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex and dependent on country and cultural context. We investigated the association between psychosocial factors and general and abdominal obesity in the Prospective Urban Rural Epidemiologic study. SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35-70 years from 628 urban and rural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education, anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression). RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body mass index ≥30 kg m(-)(2)) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress, with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (P<0.0001 for both). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stress with age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted (adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99-1.10)). There was no relationship between ethnicity- and sex-specific central obesity (adjusted PR 1.00 (0.97-1.02)). Stratification by region yielded inconsistent associations. Depression was weakly but independently linked to obesity (PR 1.08 (1.04-1.12)), and very marginally to abdominal obesity (PR 1.01 (1.00-1.03)). CONCLUSIONS: Although individuals with permanent stress tended to be slightly more obese, there was no overall independent effect and no evidence that abdominal obesity or its consequences (hypertension, diabetes) increased with higher levels of stress or depression. This study does not support a causal link between psychosocial factors and abdominal obesity.

Angiogenic imbalance and plasma lipid alterations in women with preeclampsia from a developing country.

BACKGROUND: An imbalance between anti-angiogenic factors (e.g. soluble vascular endothelial growth factor receptor-1 (s-FLT1) and soluble endoglin (s-Eng)) and pro-angiogenic factors (e.g. placental growth factor (PlGF)) as well as increased oxidized low-density lipoprotein (ox-LDL) concentrations have been associated with preeclampsia (PE). Risk factors associated with the development of PE, however, are known to be different between developed and developing countries. The aim of the study was to determine the levels of s-FLT1, s-Eng, PIGF, and ox-LDL in women with PE from a developing country. METHODS: A multi-center case-control study was conducted. One hundred and forty three women with PE were matched by age and parity with 143 healthy pregnant women without cardiovascular or endocrine diseases. Before delivery, blood samples were taken and serum was stored until analysis. RESULTS: Women with PE had lower concentrations of PIGF (p<0.0001) and higher concentrations of s-Eng (p=0.001) than healthy pregnant women. There were no differences between the groups regarding ox-LDL or s-FLT1. Women with early onset PE had higher s-FLT1 concentrations (p=0.0004) and lower PIGF concentrations (p<0.0001) than their healthy pregnant controls. Women with late onset PE had higher concentrations of s-Eng (p=0.005). Women with severe PE had higher concentrations of s-Eng (p=0.0008) and ox-LDL (p=0.01), and lower concentrations of PIGF (p<0.0001). CONCLUSIONS: Women with PE from a developing country demonstrated an angiogenic imbalance and an increased rate of LDL oxidation. Findings from this study support the theory that PE is a multifactorial disease, and understanding differences in these subpopulations may provide a better target to approach future therapies.

Increased plasma levels of total homocysteine but not asymmetric dimethylarginine in Hispanic subjects with ischemic stroke FREC-VI sub-study.

BACKGROUND AND PURPOSE: Despite sharing some metabolic and pathological mechanisms, the reported association between total homocysteine (tHcy), asymmetric dimethylarginine (ADMA) and stroke remains controversial, particularly in Hispanic populations from developing countries in which genetic, socioeconomic, and nutritional factors are different to those described in developed countries. Our objectives were to determine the relationships of these factors to stroke and to each other independent of other cardiovascular risk factors, and to explore potential sex differences. METHODS: This national (Colombia) multicenter case-control study included 238 cases and 238 controls to evaluate traditional and emerging risk factors for ischemic stroke including tHcy and ADMA plasma levels. RESULTS: The median plasma levels of tHcy were 8.48 µM for controls and 10.01 µM for cases (P<0.0001). Plasma levels of tHcy between 12 and 50µM were considered moderate hyperhomocysteinemia (HtHcy). There were no differences in plasma ADMA concentration between groups (P=0.40). Plasma levels of ADMA and creatinine were not correlated (P=0.47). After adjusting for confounding factors, the presence of HtHcy was strongly associated with stroke (OR 8.97; P<0.0001). The adjusted association between HtHcy and stroke in men (OR 9.98) was comparable to that in women (OR 8.98) (P=0.41). CONCLUSIONS: In this Hispanic population, with relatively normal renal function, plasma levels of tHcy but not ADMA were associated with stroke independent of other cardiovascular risk factors.

Nonalcoholic fatty liver disease is associated with insulin resistance in a young Hispanic population.

OBJECTIVE: To investigate whether nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) in a young Hispanic population. METHODS: A cross-sectional study was performed in Bogotá, Colombia, during 2006 in 263 males from the Colombian Air Force (age range 29-54 years). Anthropometric measurements and biochemical determinations (glycemia, lipid profile, insulin, and HOMA-IR) were obtained in order to determine the presence of metabolic syndrome (MS) criteria and insulin resistance in this population. In addition, ultrasound studies were performed to evaluate the presence of NAFLD. RESULTS: NAFLD was detected in 26.6% (n=70) of the subjects. Thirty four individuals had complete MS criteria (48.5%). The presence of NAFLD was associated with higher insulin levels (11.0±5.1 vs. 6.6±3.6, p=0.001), and its prevalence increased from 11% (n=8), to 24% (n=17) to 64% (n=45) from the lowest to the highest HOMA-IR tertile. Body mass index, triglycerides and subcutaneous and visceral fat were found to be independent predictors of NAFLD. CONCLUSIONS: These results suggest that NAFLD is associated with insulin resistance and extrahepatic adiposity in nondiabetic young Hispanic population.

Latin-American Ambulatory Blood Pressure Registry (MAPA-LATAM): An urgent need.

Hypertension (HT) is one of the main risk factors for cardiovascular disease (CVD). Although it is a global problem, independently of economic situation, region, race or culture, the data available on Latin America are limited. Clinical guidelines emphasise the importance of obtaining reliable blood pressure readings. For this reason, the use of ambulatory blood pressure monitoring (ABPM) is recommended. This improves precision and reproducibility, resulting in better diagnosing and therapeutic decision-making, and constitutes a better estimation of prognosis than office measurements. Unfortunately, there is no global prospective ABPM registry for all of Latin America that analyses HT prevalence, the level of knowledge about it, treatment percentage and the degree of control. Consequently, the authors of this article consider its implementation a priority.

Rationale and design of INTERSTROKE: a global case-control study of risk factors for stroke.

UNLABELLED: Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. METHODS: INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (+/-5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood samples and random urine samples are obtained from cases and controls. Study Significance: An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.

[Will the new figures from the AHA/ACC guidelines on the definition and treatment of hypertension in Latin America have an impact?] / ¿Repercutirán las nuevas cifras de las guías AHA/ACC en la definición y manejo de la hipertensión en Latinoamérica?

Given the fact that new guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) propose important changes in the definition of hypertension, from equal or greater than 140/90mmHg to equal or greater than 130/80mmHg, major debate has been generated about the diagnostic criteria and the treatment of high blood pressure (HBP). In addition, these guidelines recommend that in order to achieve control of hypertension the goal should be a reading lower than 130/80mmHg. These new figures will significantly increase the amount of individuals considered hypertensive, some of whom will need more medication to achieve the new goal. This paradigm has led to questioning the goal's clinical applicability given the enormous financial burden that would result from treating millions of new hypertensive patients. The academic validity of the AHA-ACC guidelines has also been questioned given the fact that the recommendations emerged basically from results obtained from a single study with important methodological differences compared to the majority of studies carried out previously. Furthermore, its outcomes are inconsistent with those of previous studies. This conflict has led to some scientific institutions, such as the Latin American Society of Hypertension (LASH), continuing to adhere to the previous recommendations.

[Measurement, monitoring and knowledge of blood pressure: May Measurement Month, Colombia 2017]. / Medición, control y conocimiento de la presión arterial: Iniciativa Mayo Mes de la Medición Colombia 2017.

AIM: To describe the findings of implementing May Measurement Month 2017 in the adult Colombian population to raise awareness of the importance of blood pressure measuring, monitoring, and awareness. MATERIALS AND METHODS: May Measurement Month is a cross-sectional survey that follows the directives of the International Society of Hypertension and the World Hypertension League, which gathers information on cardiovascular risk factors and blood pressure readings. Its implementation in Colombia was lead by the Santander Ophthalmological Foundation (FOSCAL) and the Latin American Society of Hypertension (LASH) with the support of the Colombian Network for the Prevention of Cardiovascular Diseases and Diabetes (RECARDI). RESULTS: Data was collected from 11 departments on 21,797 people, 58.7% of whom were female, with an average age of 40.5±17.7 years. The overall prevalence of high blood pressure (HBP) was 20.8% (self-reported antihypertensive treatment or systolic blood pressure reading [systolic blood pressure≥140mmHg]). Of the total number of hypertensives, 46.5% had systolic blood pressure readings classified as uncontrolled (systolic blood pressure<140mmHg), and 26.4% were unaware that they were hypertensive who, in this report, we consider to be new cases of HBP. CONCLUSION: The prevalence of (elevated) blood pressure is high in this young adult population, whose lack of awareness of HBP is also high, and HBP in those aware of their condition is poorly controlled. These results highlight the need to implement effective detection programmes for hypertensive patients and to establish standardised treatments to improve HBP control as a strategy to reduce cardiovascular events.

[The role played by the autonomic nervous system in the relation between depression and cardiovascular disease]. / Papel del sistema nervioso autónomo en la relación entre depresión y enfermedad cardiovascular.

INTRODUCTION: Findings from several epidemiological studies have revealed that major depression is associated with an increased risk of developing cardiovascular diseases (CVD) and presenting complications and new events in subjects with already-established CVD. The pathophysiological mechanisms responsible for this increased cardiovascular risk in major depression remain unclear. DEVELOPMENT: The aim of this work is to review the literature on the possible pathophysiological mechanisms involved in the relation between major depression and CVD, with special emphasis on the studies dealing with cardiovascular autonomic dysfunction and heart rate variability. Likewise, recent hypotheses concerning the neural mechanisms underlying autonomic dysfunction in subjects with major depression are also discussed. CONCLUSIONS: The evidence that is currently available allows us to hypothesise that there are anomalies in the functioning of the central autonomic neural network in subjects with major depression, and more specifically in the hippocampus, prefrontal cortex and the brain stem nuclei. Such abnormalities, in association with lower central levels of serotonin give rise to a predominance of the sympathetic flow and a loss of cardiac vagal tone. The resulting cardiovascular autonomic dysfunction could be the main cause of the increased cardiovascular risk observed in major depression. In the future, studying the autonomic nervous system may be a useful tool in the development of new therapeutic strategies aimed at reducing cardiovascular morbidity and mortality in subjects with depression.

[Factors associated to the visiting time in patients with ischaemic cerebrovascular disease]. / Factores asociados al tiempo de consulta en pacientes con enfermedad cerebrovascular isquémica.

INTRODUCTION: The high prevalence of cerebrovascular disease in underdeveloped countries has made it a public health issue. Establishing therapy within the first three hours in the case of patients with cerebrovascular disease has proved to have beneficial effects on the patient. AIM: To identify the factors associated with the time taken to visit the hospital emergency department by patients with ischaemic cerebrovascular disease in the population of Colombia. PATIENTS AND METHODS: We conducted a cross-sectional analytical study that included patients over 18 years old who had been clinically diagnosed as having an acute ischaemic cerebrovascular disease. The time between onset of symptoms and admission to the emergency department was estimated and then related to sociodemographic and cultural factors and the severity of the clinical features. RESULTS: The mean time taken to visit hospital was 17 hours and 48 minutes (standard deviation: 24 hours and 12 minutes). In 22.8% of cases the patient was admitted within the first three hours. Patients who were covered by the subsidised health care system and came from low socioeconomic classes, together with those from rural areas took longer to visit (p < 0.005). The values on the United States Institute of Health scale did not have any relation to visiting times. CONCLUSIONS: The time that elapses between the presentation of the cerebrovascular disease and visiting the emergency department in the Colombian population is high, especially among the population with lower levels of income and schooling. There is a need to implement models of education targeted towards the community and focused on the early identification of signs, symptoms and impact of cerebrovascular disease, as well as to set up a system of health care that prevents delays by coordinating resources both inside and outside hospitals.

Registro Latinoamericano de monitorización ambulatoria de la presión arterial (MAPA-LATAM): una necesidad urgente / Latin-American Ambulatory Blood Pressure Registry (MAPA-LATAM): An urgent need

La hipertensión arterial (HTA) es el principal factor de riesgo de enfermedad cardiovascular. Aunque es un problema global, independiente de la situación económica, región, raza o cultura, los datos disponibles con respecto a Latinoamérica no son muy abundantes. Por otra parte, las guías clínicas enfatizan la importancia de obtener lecturas fiables de la presión arterial. Por ello, se recomienda el uso de la monitorización ambulatoria de la presión arterial (MAPA), que mejora su precisión y reproducibilidad, ayudando a un mejor diagnóstico, en la toma de decisiones terapéuticas, y representa una mejor estimación pronóstica que las medidas en consulta. Lamentablemente, no existe ningún registro prospectivo global de MAPA para toda Latinoamérica que analice la prevalencia de HTA, el grado de su conocimiento, su porcentaje de tratamiento y el grado de control. En consecuencia, los autores de este artículo consideran prioritaria su puesta en marcha (AU)

Hypertension (HT) is one of the main risk factors for cardiovascular disease. Although it is a global problem, independently of economic situation, region, race or culture, the data available on Latin America are limited. Clinical guidelines emphasise the importance of obtaining reliable blood pressure readings. For this reason, the use of ambulatory blood pressure monitoring (ABPM) is recommended. This improves precision and reproducibility, resulting in better diagnosing and therapeutic decision-making, and constitutes a better estimation of prognosis than office measurements. Unfortunately, there is no global prospective ABPM registry for all of Latin America that analyses HT prevalence, the level of knowledge about it, treatment percentage and the degree of control. Consequently, the authors of this article consider its implementation a priority (AU)

Colombian study to assess the use of noninvasive determination of the endothelium-mediated vasodilation (CANDEV) II: does location of the occlusion device affects the accuracy of the diagnosis?

Endothelial dysfunction (ED), which is often evaluated by flow-mediated vasodilation (FMV) in the brachial artery, has been postulated as a predictor of cardiac events. Although the upper and forearm location of the occlusion device have been used for FMV evaluation, currently there is no consensus whether they provide the same information. The main goal of this study was to evaluate if both techniques have the same accuracy to differentiate subjects with and without cardiovascular risk factors (CRFs). A cross-sectional study in 124 subjects was performed. The volunteers were divided in two groups: 62 subjects (20 women and 42 men) with at least one CRF and 62 (20 women and 42 men) healthy subjects without CRFs. FMV measurements using the cuff in the upper arm and forearm with intervals of 30 min were taken. In all subjects, %FMV with the cuff located in the upper arm was 10.13 +/- 4.5 and 9.8 +/- 4.1 with the cuff located below the elbow. In healthy subjects without CRFs the %FMV in the upper arm was 12.19 +/- 4.0 versus 12.31 +/- 3.4 in the upper forearm, in CRF subjects it was 8.08 +/- 4.0 vs 7.29 +/- 3.2., respectively. FMV was not affected by the location of the cuff in maintaining the test ability and accuracy to differentiate subjects with and without CRFs.

Calcium plus linoleic acid therapy for pregnancy-induced hypertension.

OBJECTIVE: To determine the effect of dietary supplementation of calcium plus conjugated linoleic acid (calcium-CLA) in reducing the incidence of vascular endothelial dysfunction in pregnant women at high risk of developing pregnancy-induced hypertension (PIH). PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled trial conducted at 4 outpatient clinics in 2 developing countries recruited 48 healthy primigravidas younger than 19 years or older than 35 years who had a family history of pre-eclampsia and diastolic notch. Twenty-four participants received daily elemental calcium (600 mg) plus CLA (450 mg) and 24 received placebo from week 18 to 22 of pregnancy until delivery. RESULTS: Calcium-CLA supplementation reduced significantly the incidence of PIH (2 cases [8%] in the study group vs. 10 cases [42%] in the placebo group; relative risk, 0.20; 95% confidence interval, 0.05-0.82; P=.01). Endothelial dysfunction was also significantly reduced after calcium-CLA supplementation (in 18 women [75%] vs. 4 women [17%]; P<.001), compared with the placebo group (in 15 [63%] vs. 9 women [38%]; P=.08). CONCLUSION: In pregnant women at high risk for PIH, calcium-CLA supplementation decreases the incidence of PIH and improves endothelial function.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

The household economic burden of non-communicable diseases in 18 countries

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)

Is C-reactive protein an independent risk factor for essential hypertension?

CONTEXT: C-reactive protein (CRP), predicts coronary heart disease incidence in healthy subjects and has been associated with decreased endothelium-dependent relaxation, a potential risk factor for hypertension. However, the relationship between CRP and hypertension has not been studied. OBJECTIVE: To assess whether circulating levels of CRP are independently related to essential hypertension. DESIGN: Cross-sectional population survey. We measured circulating levels of CRP, blood pressure and cardiovascular risk factors among participants. Binomial regression was used to calculate the adjusted effect of CRP on the prevalence of hypertension. SETTING: General community of Bucaramanga, Colombia. PARTICIPANTS: A random sample of 300 subjects > or = 30 years old. MAIN OUTCOME MEASURE: Arterial blood pressure. RESULTS: Overall hypertension prevalence was 46.0%. The unadjusted prevalence of hypertension was 58.7% in the highest quartile of CRP, but only 34.7% in the lowest quartile. After adjustment for age, sex, body mass index, family history of hypertension, fasting glycemia, sedentary behaviour, and alcohol consumption, the prevalence of hypertension was 1.14 [95% confidence interval (CI), 0.82, 1.58; P= 0.442], 1.36 (95% CI, 0.99, 1.87; P= 0.057) and 1.56 (95% CI, 1.14, 2.13; P = 0.005) times higher in subjects in the second, third and fourth quartiles of CRP, as compared to subjects in the first quartile. CONCLUSIONS: Our results suggest, for the first time, that CRP level may be an independent risk factor for the development of hypertension. However, because of the cross-sectional nature of our study, this finding should be confirmed in prospective cohort studies, aimed at elucidating the role of CRP in the prediction, diagnosis and management of hypertension.

The crucial role of physiological Ca2+ concentrations in the production of endothelial nitric oxide and the control of vascular tone.

1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denuded donor aortae had no effect on the tone of these tissues. 3. Increasing the concentration of Ca2+ perfusing endothelium-containing donor aortae from zero to 1.25 mM caused a transient (24 +/- 9 min), concentration-dependent basal release of NO, which was attenuated at higher concentrations of Ca2+ (1.5-2.0 mM). 4. The duration of the effect of Ca2+ on the basal release of NO was increased by a concomitant infusion of L-arginine (100 microM) through the donor aorta. 5. Changes in the concentration of Ca2+ between 0.5 and 2.0 mM had a similar biphasic effect on the release of NO induced by ACh, which was also maximal at 1.25 mM Ca2+. 6. When Ca2+ was removed from the Krebs buffer perfusing the donor aorta, the basal release of NO declined within 2 min. In contrast, the release of NO induced by ACh declined progressively over 60 min. 7. Thus changes in the concentration of Ca2+ around the physiological range modulate the synthesis of NO by the vascular endothelium and consequently, vascular tone. This may account for the effects of dietary Ca2+ supplements on the control of some hypertensive states.

Improvement in functions of the central nervous system by estrogen replacement therapy might be related with an increased nitric oxide production.

Estrogen promotes neurons growth, prevents neuronal cell atrophy and regulates synaptic plasticity. Administration of estrogen protects neurons against oxidative stress, excitotoxins, and beta-amyloid-induced toxicity in cell culture. It has been shown that estrogen treatment reduces the serum monoamino oxidase levels and might regulate learning and memory. Nitric oxide (NO) is a retrograde messenger and long-term potentiation can be block using NO-synthase inhibitors or can be prevent with NO-scavengers. NO synthase is widespread in the central nervous system and acts as neurotransmitter/neuromodulator. The actions of serotonin, bradykinin, endothelin, acetylcholine and noradrenaline might be linked to NO formation. Estrogen induces activity of constitutive NO synthase and estrogen replacement therapy in postmenopausal women increases significantly circulating nitrite plus nitrate levels. The effect of estrogen on NO synthesis is rapid and is maintained with repeated administration. We demonstrated the effects of estrogen replacement therapy in Andean postmenopausal women were associated with a significantly increase in plasma levels of nitrite plus nitrate. Our hypothesis is that beneficial effect of estrogen replacement therapy on involutive depression in postmenopausal women is mediated by increase in NO production by central nervous system.