Associations of general and central adiposity with hypertension and cardiovascular disease among South Asian populations: a systematic review and meta-analysis.

BACKGROUND: The relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South Asian populations, who characteristically manifest larger waist circumferences (WC) for equivalent body mass index (BMI). This systematic review and meta-analysis provide an overview of the literature on the association of different anthropometric measures with CVD risk among South Asians. METHODOLOGY: MEDLINE and Embase were searched from 1990 to the present for studies in South Asian populations investigating associations of two or more adiposity measures with CVD. Random-effects meta-analyses were conducted on the associations of BMI, WC and waist-to-hip ratio (WHR) with blood pressure, hypertension and CVD. Quality assessment was performed using the Newcastle-Ottawa scale. RESULTS: Titles and abstracts were screened for 7327 studies, yielding 147 full-text reviews. The final sample (n=30) included 2 prospective, 5 case-control and 23 cross-sectional studies. Studies reported generally higher risks of hypertension and CVD at higher adiposity levels. The pooled mean difference in systolic blood pressure (SBP) per 5 kg/m2 higher BMI was 3 mmHg (2.90 (95% CI 1.30 to 4.50)) and 6 mmHg (6.31 (95% CI 4.81 to 7.81) per 13 cm larger WC. The odds ratio (OR) of hypertension per 5 kg/m2 higher BMI was 1.33 (95% CI 1.18 to 1.51), 1.45 (95% CI 1.05 to 1.98) per 13 cm larger WC and 1.22 (95% CI 1.04 to 1.41) per 0.1-unit larger WHR. Pooled risk of CVD for BMI-defined overweight versus healthy-weight was 1.65 (95% CI 1.55 to 1.75) and 1.48 (95% CI 1.21 to 1.80) and 2.51 (95% CI 0.94 to 6.69) for normal versus large WC and WHR, respectively. Study quality was average with significant heterogeneity. CONCLUSIONS: Measures of both general and central adiposity had similar, strong positive associations with the risk of CVD in South Asians. Larger prospective studies are required to clarify which measures of body composition are more informative for targeted CVD primary prevention in this population.

Body Composition and Risk of Incident Heart Failure in 1 Million Adults: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background The aim of this systematic review was to quantify the associations between body composition measures and risk of incident heart failure (HF) and its subtypes in the general population. Methods and Results We searched Medline, Embase, and Global Health databases from each database inception to January 19, 2023 for prospective studies reporting on body composition and HF risk. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies. Fixed-effects models were used for meta-analysis. Thirty-five studies were included (ntotal=1 137 044; ncases=34 422). Summary relative risk (RR) per 5-kg/m2 higher body mass index was 1.42 (95% CI, 1.40-1.42; 𝜁2=0.02, I2=94.4%), 1.28 (95% CI, 1.26-1.31; 𝜁2=0.01, I2=75.8%) per 10-cm higher waist circumference, and 1.33 (95% CI, 1.28-1.37; 𝜁2=0.04, I2=94.9%) per 0.1-unit higher waist-hip ratio. Pooled estimates of the few studies that reported on regional fat suggested significant positive association between HF risk and both visceral fat (RR, 1.08 [95% CI, 1.04-1.12]) and pericardial fat (RR, 1.08 [95% CI, 1.06-1.10]). Among HF subtypes, associations were stronger for HF with preserved ejection fraction than HF with reduced ejection fraction. No study reported on lean mass. Conclusions Pooled data suggested strong associations between adiposity and HF. The association with adiposity is stronger for HF with preserved ejection fraction than HF with reduced ejection fraction, indicating that different mechanisms may be at play in etiopathogenesis of HF subtypes. Future studies are needed to investigate role of regional fat mass and lean mass in HF risk. Registration Information REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42020224584.

Secondhand smoke exposure is independently associated with stroke among non-smoking adults in West Africa.

BACKGROUND: Stroke is a leading cause of disability and mortality worldwide, but little is known about the contribution of secondhand smoke exposure (SHSE) to stroke epidemiology among indigenous Africans. OBJECTIVE: To evaluate the association of SHSE with stroke among indigenous Africans. METHODS: We analyzed the relationship of SHSE with stroke among 2990 case-control pairs of adults who had never smoked (identified in the SIREN study) using conditional logistic regression at a two-sided P < 0.05. RESULTS: Multivariable-adjusted odds ratio and 95% confidence interval; 1.25 (1.04, 1.50; P = 0.02) revealed SHSE was positively associated with stroke independent of stroke subtypes. CONCLUSION: Culturally relevant primary prevention strategies targeted at SHSE might be promising in preventing stroke among Africans.

Anti-angiogenesis in cancer therapeutics: the magic bullet.

BACKGROUND: Angiogenesis is the formation of new vascular networks from preexisting ones through the migration and proliferation of differentiated endothelial cells. Available evidence suggests that while antiangiogenic therapy could inhibit tumour growth, the response to these agents is not sustained. The aim of this paper was to review the evidence for anti-angiogenic therapy in cancer therapeutics and the mechanisms and management of tumour resistance to antiangiogenic agents. We also explored the latest advances and challenges in this field. MEDLINE and EMBASE databases were searched for publications on antiangiogenic therapy in cancer therapeutics from 1990 to 2020. Vascular endothelial growth factor (VEGF) is the master effector of the angiogenic response in cancers. Anti-angiogenic agents targeting the VEGF and HIF-α pathways include monoclonal antibodies to VEGF (e.g. bevacizumab), small-molecule tyrosine kinase inhibitors (TKIs) e.g. sorafenib, decoy receptor or VEGF trap e.g. aflibercept and VEGFR2 inhibitors (e.g. ramucirumab). These classes of drugs are vascular targeting which in many ways are advantageous over tumour cell targeting drugs. Their use leads to a reduction in the tumour blood supply and growth of the tumour blood vessels. Tumour resistance and cardiovascular toxicity are important challenges which limit the efficacy and long-term use of anti-angiogenic agents in cancer therapeutics. Tumour resistance can be overcome by dual anti-angiogenic therapy or combination with conventional chemotherapy and immunotherapy. Emerging nanoparticle-based therapy which can silence the expression of HIF-α gene expression by antisense oligonucleotides or miRNAs has been developed. Effective delivery platforms are required for such therapy. SHORT CONCLUSION: Clinical surveillance is important for the early detection of tumour resistance and treatment failure using reliable biomarkers. It is hoped that the recent interest in mesenchymal cell-based and exosome-based nanoparticle delivery platforms will improve the cellular delivery of newer anti-angiogenics in cancer therapeutics.

Cardiovascular Safety and Superiority of Anti-Obesity Medications.

Over the past few decades, several anti-obesity medications have demonstrated an association with adverse cardiovascular outcomes, leading to their market withdrawal. This has caused researchers to investigate the cardiovascular safety of such medications in cardiovascular outcome trials. However, the data from these trials are limited, and their outcomes are not promising. Therefore, the aim of this review is to provide an overview of the current and past Food and Drug Administration-approved medications for weight loss, including novel diabetes medications (glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) and non-diabetes medications, and to highlight the current designs of cardiovascular outcome trials and their importance in the evaluation of the overall safety concerns associated with these anti-obesity medications. The limitations of the trials and opportunities for improvement were also evaluated. Finally, we also briefly describe cardiovascular safety and risks in this review.

Body composition and risk of heart failure: protocol for a systematic review and meta-analysis.

INTRODUCTION: Although there is strong evidence of an association between general adiposity and incidence of heart failure, previous systematic reviews and meta-analyses have not reliably assessed the association of heart failure risk with other aspects of body composition (such as body fat distribution or lean mass), or between body composition and risk of heart failure subtypes. We aim to conduct a systematic review and meta-analysis of prospective studies to address these uncertainties, and inform efforts to prevent and treat heart failure. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots. ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media. PROSPERO REGISTRATION NUMBER: CRD42020224584.

Risk factors of heart failure among patients with hypertension attending a tertiary hospital in Ibadan, Nigeria: The RISK-HHF case-control study.

AIM: Hypertension is the leading cause of heart failure (HF) in sub-Saharan Africa. Preventive public health approach to reduce the scourge of HF must seek to understand the risk factors of HF in at-risk populations. The aim of this study was to characterize the risk factors of HF among patients with hypertension attending a cardiology clinic. METHODS AND RESULTS: One hundred and one (101) case-control age- and sex-matched pairs were recruited. The study population were adults with a clinical diagnosis of hypertensive HF (cases) and individuals with systemic hypertension without HF. They were interviewed and evaluated for cardiovascular risk factors. Associations between variables were tested with chi square test, Fisher's exact test and independent sample t test as appropriate. Logistic regression modelling was used to determine the independent risk factors of hypertensive HF (HHF) in the study population while 'punafcc' package in stata12 was used to calculate the population attributable fraction (PAF) of the risk factors. Suboptimal medication adherence was the strongest adverse risk factor of HHF (medium adherence aOR: 3.53, 95%CI: 1.35-9.25; low adherence aOR: 9.44, 95%CI: 3.41-26.10) with a PAF of 67% followed by dipstick proteinuria (aOR: 4.22, 95%CI: 1.62-11.02; PAF: 34%) and alcohol consumption/day per 10grams (aOR: 1.23, 95%CI: 1.02-1.49; PAF: 22%). The protective risk factors of HHF were use of calcium channel blockers (aOR 0.25, 95%CI: 0.11-0.59; PAF: 59%), then daily fruits and vegetable consumption (aOR 0.41, 95%CI: 0.17-1.01; PAF: 46%), and eGFR (aOR 0.98, 95%CI: 0.96-0.99; PAF: 5.3%). CONCLUSIONS: The risk factors of HHF are amenable to lifestyle and dietary changes. Public health interventions and preventive cardiovascular care to improve medication adherence, promote fruit and vegetable consumption and reduce alcohol consumption among patients with hypertension are recommended. Renoprotection has utility in the prevention of HF among hypertensives.

Development and Validation of a Electrocardiographic Diagnostic Score of Heart Failure Among Patients with Hypertension Attending a Tertiary Hospital in Ibadan, Nigeria: The RISK-HHF Case-Control Study.

OBJECTIVES: Hypertension is the leading cause of HF in sub-Saharan Africa. Electrocardiography (ECG) is a cheap and easily available stratification tool for the diagnosis and prognostication of individuals with hypertension. The aim of this study was to develop an ECG-based HF diagnostic score among patients with hypertension attending a specialist cardiology clinic. METHODS: One hundred and one (101) case-control age- and sex-matched pairs were recruited. The study population were adults with a clinical diagnosis of hypertensive HF failure (cases) and systemic hypertension without HF (controls). Participants underwent clinical assessment and ECG. Associations between ECG variables and HF risk were tested with chi square test. Logistic regression modelling (age- and sex adjusted) was trained on a random subset of participants and tested on the remaining participants to determine the ECG abnormalities that are diagnostic of HF and develop a HF diagnostic score. The HF diagnostic score was then validated in an independent dataset of the ECG-Hypertension Audit. Goodness of fit and c-statistics of the HF summed diagnostic score in the training, testing and validation datasets are presented. A two-sided p value of <0.05 was considered statistically significant. RESULTS: The independent ECG diagnostic markers of HF among hypertensive patients in this study in decreasing order of effect size were sinus tachycardia (aOR: 7.72, 95% CI: 2.31-25.85). arrhythmia (aOR: 7.14, 95% CI: 2.57-19.86), left ventricular hypertrophy (aOR: 4.47; 1.85-10.77) and conduction abnormality (aOR: 3.41, 95% CI: 1.21-9.65). The HF summed diagnostic score showed excellent calibration and discrimination in the training (Hosmer Lemeshow p = 0.90; c-statistic 0.82; 95% CI 0.76-0.89) and test samples (Hosmer Lemeshow p=0.31; c-statistic 0.73 95% CI 0.60 to 0.87) of the derivation cohort and an independent validation audit cohort (Hosmer Lemeshow p = 0.17; c-statistic 0.79 95% CI 0.74 to 0.84) respectively. The model showed high diagnostic accuracy in individuals with different intermediate pre-test probabilities of HF. CONCLUSIONS: A ECG based HF score consisting of sinus tachycardia, arrhythmia, conduction abnormality and left ventricular hypertrophy is diagnostic of HF especially in those with intermediate pre-test probability of HF. This has clinical importance in the stratification of individuals with systemic hypertension.