Circulating biomarkers in the early detection of hypertensive heart disease: usefulness in the developing world.

Although the varying phenotypic spectra of hypertensive heart disease (HHD) can be assessed by electrocardiography (ECG), echocardiography and cardiovascular magnetic resonance (CMR), ECG criteria for left ventricular hypertrophy (LVH) are insensitive, while echocardiography and CMR are expensive, less readily available and often lack requisite expertise. Consequently, the use of circulating biomarkers in the diagnosis and prognostication of HHD beyond the traditional N-terminal pro- b-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) have become an attractive alternative. We carried out a PubMed and Google Scholar databases' search of original articles on circulating biomarkers used in the diagnosis of the different spectrum of HHD over the last 10 years [2005-2015] in humans. Fourteen studies met the inclusion criteria with NT-pro BNP being the most studied circulating biomarker in HHD followed by soluble ST2 (sST2). There is a lack of data on the use of circulating biomarkers in HHD. There is a need to explore further this area of investigative cardiology.

A diagnostic algorithm for pulmonary hypertension due to left heart disease in resource-limited settings: can busy clinicians adopt a simple, practical approach?

Pulmonary hypertension (PH) has progressively moved from an orphan disease to a significant global health problem with a major disease burden in limited7hyphen;resource countries, where over 97% of patients live. The aetiologies of PH differ between high- and low-income nations, but PH due to left heart disease is credited to be the most frequent contemporary form. Although a straightforward diagnosis of PH requires the use of right heart catheterisation (RHC), access to equipment for RHC is a deterrent. Furthermore, the risk associated with RHC limits its uptake to a selection of specialised centres. Moreover, the rigour and clinical reasoning for diagnosis in clinical medicine is rapidly changing and revealing that PH can complicate a diverse range of medical conditions needing other explorations. In this article, we provide for the busy clinician, a simplified diagnostic algorithm for PH that is relevant for making a correct early diagnosis and limiting the impact of PH.

The effect of lifestyle interventions on maternal body composition during pregnancy in developing countries: a systematic review.

Optimal maternal body composition during pregnancy is a public health priority due to its implications on maternal health and infant development. We therefore aimed to conduct a systematic review of randomised, controlled trials, and case-control and cohort studies using lifestyle interventions to improve body composition in developing countries. Of the 1 708 articles that were searched, seven studies, representing three countries (Brazil, Iran and Argentina), were included in the review. Two articles suggested that intervention with physical activity during pregnancy may significantly reduce maternal weight gain, and five studies were scored as being of poor quality. This systematic review highlights the lack of research within developing countries on lifestyle interventions for the management of excessive weight gain during pregnancy. Similar reviews from developed countries demonstrate the efficacy of such interventions, which should be confirmed using well-designed studies with appropriate intervention methods in resource-limited environments.

Primary care in the prevention, treatment and control of cardiovascular disease in sub-Saharan Africa.

Cardiovascular disease (CVD) is the frontrunner in the disease spectrum of sub-Saharan Africa, with stroke and ischaemic heart disease ranked seventh and 14th as leading causes of death, respectively, on this sub-continent. Unfortunately, this region is also grappling with many communicable, maternal, neonatal and nutritional disorders. Limited resources and the high cost of CVD treatment necessitate that primary prevention should have a high priority for CVD control in sub-Saharan Africa. One major challenge of such an approach is how to equip primary care to respond promptly and effectively to this burden. We present a practical approach on how primary care in sub-Saharan Africa could effectively address the prevention, treatment and control of CVD on the subcontinent. For effective prevention, control and treatment of CVD in sub-Saharan Africa, there should be strategic plans to equip primary care clinics with well-trained allied healthcare workers who are supervised by physicians.

Review of a causal role of fructose-containing sugars in myocardial susceptibility to ischemia/reperfusion injury.

In 2012, the World Health Organization Global Status Report on noncommunicable diseases showed that 7.4 million deaths were due to ischemic heart disease. Consequently, cardiovascular disease is a significant health burden, especially when partnered with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Of note, these diseases can all be induced or exacerbated by diet. Carbohydrates, in particular, fructose and glucose, generally form the largest part of the human diet. Accumulating evidence from animal studies suggests that if large amounts of fructose are consumed either in isolation or in combination with glucose (fructose-containing sugars), myocardial susceptibility to ischemia/reperfusion (I/R) injury increases. However, the underlying mechanisms that predisposes the myocardium to I/R injury in the fructose model are not elucidated, and no single mechanistic pathway has been described. Based on all available data on this topic, this review describes previously investigated mechanisms and highlights 3 main mechanistic pathways whereby fructose has shown to increase myocardial susceptibility to I/R injury. These pathways include (1) increased reactive oxygen species, resulting in reduced nitric oxide synthase and coronary flow; (2) elevated plasma fatty acids and insulin, leading to increased cardiac triglyceride content and lipotoxicity; and (3) disrupted myocardial calcium handling/homeostasis. Moreover, we highlight various factors that should be taken into account when the fructose animal model is used, such as rat strain, treatment periods, and doses. We argue that failure to do so would result in erratic inferences drawn from the existing body of evidence on fructose animal models.

Role of toll-like receptor 4 in melatonin-induced cardioprotection.

Melatonin protects the heart against myocardial ischemia/reperfusion injury via the activation of the survivor activating factor enhancement (SAFE) pathway which involves tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Toll-like receptor 4 (TLR4) plays a crucial role in myocardial ischemia/reperfusion injury and activates TNFα. In this study, we investigated whether melatonin may target TLR4 to activate the SAFE pathway. Isolated hearts from rats or mice were subjected to ischemia/reperfusion injury. Melatonin (75 ng/L) and/or TAK242 (a specific inhibitor of TLR4 signaling, 500 nm) were administered to the rat hearts before the induction of ischemia. Pre-ischemic myocardial STAT3 was evaluated by Western blotting. Lipopolysaccharide (LPS, a stimulator of TLR4) was administered to wild type, TNFα receptor 2 knockout or cardiomyocyte-specific STAT3-deficient mice (2.8 mg/kg, i.p) 45 min before the heart isolation. Myocardial infarct size was measured as an endpoint. Compared to the control, administration of melatonin reduced myocardial infarct size (34.7 ± 2.8% versus 62.6 ± 2.7%, P < 0.01). This protective effect was abolished in the presence of TAK242 (49.2 ± 6.5%). Melatonin administered alone increased the pre-ischemic activation of mitochondrial STAT3, and this effect was attenuated with TAK242. Furthermore, stimulation of TLR4 with LPS pretreatment to mice reduced myocardial infarct size of the hearts isolated from wild-type animals but failed to protect the hearts isolated from TNFα receptor 2-knockout mice or cardiomyocyte-specific STAT3-deficient mice (P < 0.001). Taken together, these data suggest that cardioprotection induced by melatonin is mediated by TLR4 to activate the SAFE pathway.

A systematic review of factors that affect uptake of community-based health insurance in low-income and middle-income countries.

BACKGROUND: Low-income and middle-income countries (LMICs) have difficulties achieving universal financial protection, which is primordial for universal health coverage. A promising avenue to provide universal financial protection for the informal sector and the rural populace is community-based health insurance (CBHI). We systematically assessed and synthesised factors associated with CBHI enrolment in LMICs. METHODS: We searched PubMed, Scopus, ERIC, PsychInfo, Africa-Wide Information, Academic Search Premier, Business Source Premier, WHOLIS, CINAHL, Cochrane Library, conference proceedings, and reference lists for eligible studies available by 31 October 2013; regardless of publication status. We included both quantitative and qualitative studies in the review. RESULTS: Both quantitative and qualitative studies demonstrated low levels of income and lack of financial resources as major factors affecting enrolment. Also, poor healthcare quality (including stock-outs of drugs and medical supplies, poor healthcare worker attitudes, and long waiting times) was found to be associated with low CBHI coverage. Trust in both the CBHI scheme and healthcare providers were also found to affect enrolment. Educational attainment (less educated are willing to pay less than highly educated), sex (men are willing to pay more than women), age (younger are willing to pay more than older individuals), and household size (larger households are willing to pay more than households with fewer members) also influenced CBHI enrolment. CONCLUSION: In LMICs, while CBHI schemes may be helpful in the short term to address the issue of improving the rural population and informal workers' access to health services, they still face challenges. Lack of funds, poor quality of care, and lack of trust are major reasons for low CBHI coverage in LMICs. If CBHI schemes are to serve as a means to providing access to health services, at least in the short term, then attention should be paid to the issues that militate against their success.

Is There an Association between Sleeping Patterns and Other Environmental Factors with Obesity and Blood Pressure in an Urban African Population?

Beyond changing dietary patterns, there is a paucity of data to fully explain the high prevalence of obesity and hypertension in urban African populations. The aim of this study was to determine whether other environmental factors (including sleep duration, smoking and physical activity) are related to body anthropometry and blood pressure (BP). Data were collected on 1311 subjects, attending two primary health care clinics in Soweto, South Africa. Questionnaires were used to obtain data on education, employment, exercise, smoking and sleep duration. Anthropometric and BP measurements were taken. Subjects comprised 862 women (mean age 41 ± 16 years and mean BMI 29.9 ± 9.2 kg/m²) and 449 men (38 ± 14 years and 24.8 ± 8.3 kg/m²). In females, ANOVA showed that former smokers had a higher BMI (p<0.001) than current smokers, while exposure to second hand smoking was associated with a lower BMI (p<0.001) in both genders. Regression analyses demonstrated that longer sleep duration was associated with a lower BMI (p<0.05) in older females only, and not in males, whilst in males napping during the day for > 30 minutes was related to a lower BMI (ß = -0.04, p<0.01) and waist circumference (ß = -0.03, p<0.001). Within males, napping for >30 minutes/day was related to lower systolic (ß = -0.02, p<0.05) and lower diastolic BP (ß = -0.02, p = 0.05). Longer night time sleep duration was associated with higher diastolic (ß = 0.005, p<0.01) and systolic BP (ß = 0.003, p<0.05) in females. No health benefits were noted for physical activity. These data suggest that environmental factors rarely collected in African populations are related, in gender-specific ways, to body anthropometry and blood pressure. Further research is required to fully elucidate these associations and how they might be translated into public health programs to combat high levels of obesity and hypertension.

Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine.

We have recently discovered that melatonin, given acutely and directly to the isolated heart at the concentration found in wine, confers cardioprotection against ischemia-reperfusion (I/R). However, whether the presence of melatonin in wine contributes to the cardioprotective effect of chronic and moderate consumption of wine and its signalling mechanisms of protection are unknown. We therefore used both in vivo and in vitro models of I/R to investigate whether the presence of melatonin in red wine may contribute to the cardioprotective effect of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice (WT) received drinking water supplemented daily with a moderate amount of red wine or melatonin given at the concentration found in the red wine. Rats were also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and 2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of melatonin receptor type 3 (2.5 mg/kg/day, intraperitoneally). After 14 days, hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct size in both rats and WT mice (p < 0.001). Luzindole did not affect wine-induced cardioprotection, while prazosin reduced the infarct sparing effect of red wine (p < 0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs. control). Our novel findings suggest that the presence of melatonin in red wine contributes to the cardioprotective effect of chronic and moderate consumption of red wine against lethal I/R injuries. This effect is most likely mediated, at least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both key players of the prosurvival and well described SAFE pathway.

Low systolic blood pressure and high resting heart rate as predictors of outcome in patients with peripartum cardiomyopathy.

BACKGROUND: Patients with peripartum cardiomyopathy (PPCM) present with low blood pressure (SBP) often preventing uptitration of heart failure medication. We aimed to study prediction of risk and the contribution of high resting heart rate (HR) and low SBP to risk in recent onset of PPCM. METHODS: Clinical assessment with HR and SBP, echocardiography and laboratory results were obtained at baseline and at six months on 206 patients with recent onset PPCM enrolled at two tertiary care centers in South Africa. Poor outcome was defined as the combined endpoint of death, LVEF<35% or remaining in New York Heart Association (NYHA) functional class III/IV at six months. Complete LV recovery was defined as LVEF ≥ 55% at six months. RESULTS: Poor outcome was observed in 110 of 220 patients (53%), with 26 patients dying at six months (12.6%). There were 98 (47.5%) patients with SBP ≤ 110 mmHg. Patients with high HR (HR ≥ 100) and low SBP (< 110 mmHg) tended to have worse outcomes than patients below the HR median and high SBP. PPCM patients with low SBP and high HR were less likely to be on ACE-inhibitors (n = 35, 69% versus n = 129, 84%, p = 0.024) and on the beta blocker carvedilol (n = 24, 47% versus n = 98, 64%, p = 0.047). Low SBP, high HR and left ventricular end diastolic diameter at baseline were predictors of poor outcome. Patients with low SBP and high HR had the highest mortality (p = 0.0023). CONCLUSIONS: These findings suggest increased risk in patients with PPCM presenting with low SBP and high HR on standard heart failure medication possibly having implications on HF management.

Factors that affect the uptake of community-based health insurance in low-income and middle-income countries: a systematic protocol.

INTRODUCTION: Many people residing in low-income and middle-income countries (LMICs) are regularly exposed to catastrophic healthcare expenditure. It is therefore pertinent that LMICs should finance their health systems in ways that ensure that their citizens can use needed healthcare services and are protected from potential impoverishment arising from having to pay for services. Ways of financing health systems include government funding, health insurance schemes and out-of-pocket payment. A health insurance scheme refers to pooling of prepaid funds in a way that allows for risks to be shared. The health insurance scheme particularly suitable for the rural poor and the informal sector in LMICs is community-based health insurance (CBHI), that is, insurance schemes operated by organisations other than governments or private for-profit companies. We plan to search for and summarise currently available evidence on factors associated with the uptake of CBHI, as we are not aware of previous systematic reviews that have looked at this important topic. METHODS: This is a protocol for a systematic review of the literature. We will include both quantitative and qualitative studies in this review. Eligible quantitative studies include intervention and observational studies. Qualitative studies to be included are focus group discussions, direct observations, interviews, case studies and ethnography. We will search EMBASE, PubMed, Scopus, ERIC, PsycInfo, Africa-Wide Information, Academic Search Premier, Business Source Premier, WHOLIS, CINAHL and the Cochrane Library for eligible studies available by 31 October 2013, regardless of publication status or language of publication. We will also check reference lists of included studies and proceedings of relevant conferences and contact researchers for eligible studies. Two authors will independently screen the search output, select studies and extract data, resolving discrepancies by consensus and discussion. Qualitative data will be extracted using standardised data extraction tools adapted from the Critical Appraisal Skills Program (CASP) qualitative appraisal checklist and put together in a thematic analysis where applicable. We will statistically pool data from quantitative studies in a meta-analysis; but if included quantitative studies differ significantly in study settings, design and/or outcome measures, we will present the findings in a narrative synthesis. This protocol has been registered with PROSPERO (ID=CRD42013006364). DISSEMINATION: Recommendations will be made to health policy makers, managers and researchers in LMICs to help inform them on ways to strengthen and increase the uptake of CBHI.

Lowering the alcohol content of red wine does not alter its cardioprotective properties.

BACKGROUND: Many epidemiological, clinical and laboratory studies suggest that chronic and moderate consumption of red wine benefits cardiovascular health, because of the alcoholic content or the polyphenols/flavonoids. AIMS: The antioxidant and cardioprotective properties of a French red wine (cabernet sauvignon, 12% alcohol by volume) were compared with those of the same wine subjected to reverse osmosis for partial removal of alcohol (6% alcohol by volume). METHODS: Antioxidant capacity was assessed in vitro using the oxygen radical absorbance capacity (ORAC) assay. To test the cardioprotective effect of 12% v. 6% wine, the drinking water of rats used for controls was supplemented with red wine (12% or 6%). After 10 days, hearts were isolated on a Langendorff system and subjected to 30 minutes of global ischaemia plus 30 minutes of reperfusion (I/R). RESULTS: No differences in antioxidant capacity were observed between wine of 12% and 6% alcohol content (n=8 per group). Control hearts subjected to I/R presented a rate pressure product (heart rate x left ventricular developed pressure, expressed as a percentage of baseline value) of 16±4% (mean±standard error). Pretreatment with wine 12% or 6% improved the rate pressure product to 40±6% and 43±6%, respectively (p<0.05 v. control). CONCLUSION: Our findings suggest that the reduction of alcohol content from 12% to 6% in wine did not alter its antioxidant and cardioprotective properties. Moderate and regular consumption of lower alcohol content wines may confer beneficial effects without the risks associated with traditional wines of higher alcohol content.

Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection.

Epidemiological studies suggest that regular moderate consumption of red wine confers cardioprotection but the mechanisms involved in this effect remain unclear. Recent studies demonstrate the presence of melatonin in wine. We propose that melatonin, at a concentration found in red wine, confers cardioprotection against ischemia-reperfusion injury. Furthermore, we investigated whether both melatonin and resveratrol protect via the activation of the newly discovered survivor activating factor enhancement (SAFE) prosurvival signaling pathway that involves the activation of tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Isolated perfused male mouse (wild type, TNFα receptor 2 knockout mice, and cardiomyocyte-specific STAT3-deficient mice) or rat hearts (Wistars) were subjected to ischemia-reperfusion. Resveratrol (2.3 mg/L) or melatonin (75 ng/L) was perfused for 15 min with a 10-min washout period prior to an ischemia-reperfusion insult. Infarct size was measured at the end of the protocol, and Western blot analysis was performed to evaluate STAT3 activation prior to the ischemic insult. Both resveratrol and melatonin, at concentrations found in red wine, significantly reduced infarct size compared with control hearts in wild-type mouse hearts (25 ± 3% and 25 ± 3% respectively versus control 69 ± 3%, P < 0.001) but failed to protect in TNF receptor 2 knockout or STAT3-deficient mice. Furthermore, perfusion with either melatonin or resveratrol increased STAT3 phosphorylation prior to ischemia by 79% and 50%, respectively (P < 0.001 versus control). Our data demonstrate that both melatonin and resveratrol, as found in red wine, protect the heart in an experimental model of myocardial infarction via the SAFE pathway.

Ethanolamine is a novel STAT-3 dependent cardioprotective agent.

Ethanolamine is a biogenic amine found naturally in the body as part of membrane lipids and as a metabolite of the cardioprotective substances, sphingosine-1-phosphate (S1P) and anandamide. In the brain, ethanolamine, formed from the breakdown of anandamide protects against ischaemic apoptosis. However, the effects of ethanolamine in the heart are unknown. Signal transducer and activator of transcription 3 (STAT-3) is a critical prosurvival factor in ischaemia/reperfusion (I/R) injury. Therefore, we investigated whether ethanolamine protects the heart via activation of STAT-3. Isolated hearts from wildtype or cardiomyocyte specific STAT-3 knockout (K/O) mice were pre-treated with ethanolamine (Etn) (0.3 mmol/L) before I/R insult. In vivo rat hearts were subjected to 30 min ischaemia/2 h reperfusion in the presence or absence of 5 mg/kg S1P and/or the FAAH inhibitor, URB597. Infarct size was measured at the end of each protocol by triphenyltetrazolium chloride staining. Pre-treatment with ethanolamine decreased infarct size in isolated mouse or rat hearts subjected to I/R but this infarct sparing effect was lost in cardiomyocyte specific STAT-3 deficient mice. Pre-treatment with ethanolamine increased nuclear phosphorylated STAT-3 [control 0.75 ± 0.08 vs. Etn 1.50 ± 0.09 arbitrary units; P < 0.05]. Our findings suggest a novel cardioprotective role for ethanolamine against I/R injury via activation of STAT-3.