Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension.

Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, nondipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours. These observations provide justification for complete 24-h BP control as being the primary goal of antihypertensive treatment. Bedtime administration of antihypertensive drugs has also been proposed as a potentially more effective treatment strategy than morning administration. This Position Paper by the International Society of Hypertension reviewed the published evidence on the clinical relevance of the diurnal variation in BP and the timing of antihypertensive drug treatment, aiming to provide consensus recommendations for clinical practice. Eight published outcome hypertension studies involved bedtime dosing of antihypertensive drugs, and all had major methodological and/or other flaws and a high risk of bias in testing the impact of bedtime compared to morning treatment. Three ongoing, well designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing. Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose.

Registry for Acute Coronary Events in Nigeria (RACE-Nigeria): Clinical Characterization, Management, and Outcome.

Background Coronary artery disease was hitherto a rarity in Africa. Acute coronary syndrome (ACS) accounts for coronary artery disease-related morbidity and mortality. Reports on ACS in Africa are few. Methods and Results We enrolled 1072 indigenous Nigerian people 59.2±12.4 years old (men, 66.8%) with ACS in an observational multicentered national registry (2013-2018). Outcome measures included incidence, intervention times, reperfusion rates, and 1-year mortality. The incidence of ACS was 59.1 people per 100 000 hospitalized adults per year, and comprised ST-segment-elevation myocardial infarction (48.7%), non-ST-segment-elevation myocardial infarction (24.5%), and unstable angina (26.8%). ACS frequency peaked 10 years earlier in men than women. Patients were predominantly from urban settings (87.3%). Median time from onset of symptoms to first medical contact (patients with ST-segment-elevation myocardial infarction) was 6 hours (interquartile range, 20.1 hours), and only 11.9% presented within a 12-hour time window. Traditional risk factors of coronary artery disease were observed. The coronary angiography rate was 42.4%. Reperfusion therapies included thrombolysis (17.1%), percutaneous coronary intervention (28.6%), and coronary artery bypass graft (11.2%). Guideline-based pharmacotherapy was adequate. Major adverse cardiac events were 30.8%, and in-hospital mortality was 8.1%. Mortality rates at 30 days, 3 months, 6 months, and 1 year were 8.7%, 9.9%, 10.9%, and 13.3%, respectively. Predictors of mortality included resuscitated cardiac arrest (odds ratio [OR], 50.0; 95% CI, 0.010-0.081), nonreperfusion (OR, 34.5; 95% CI, 0.004-0.221), pulmonary edema (OR, 11.1; 95% CI, 0.020-0.363), left ventricular diastolic dysfunction (OR, 4.1; 95% CI, 0.091-0.570), and left ventricular systolic dysfunction (OR, 2.1; 95% CI, 1.302-3.367). Conclusions ACS burden is rising in Nigeria, and patients are relatively young and from an urban setting. The system of care is evolving and is characterized by lack of capacity and low patient eligibility for reperfusion. We recommend preventive strategies and health care infrastructure-appropriate management guidelines.

Inclusion in the World Health Organization Model List of Essential Medicines of Non-Vitamin K Anticoagulants for Treatment of Non-Valvular Atrial Fibrillation: A Step Towards Reducing the Burden of Cardiovascular Morbidity and Mortality.

Non-vitamin K antagonist oral anticoagulants (NOACs) represent a paradigm shift in the treatment of non-valvular atrial fibrillation (AF) with major practice guidelines around the world recommending NOACs over vitamin K antagonist oral anticoagulants for initial treatment of AF for stroke prevention. Here we describe the evidence collated and the process followed for the successful inclusion of NOACs into the 21st WHO Model List of Essential Medicines (EML). Individual NOACs have been reported to be non-inferior or superior to warfarin in preventing stroke and systemic embolism in eligible AF patients with a reduction in the risk of stroke and systemic embolism and a lower risk of major bleeding in patients with non-valvular AF compared with warfarin in both RCTs and real-world data. The successful inclusion of NOACs in the WHO EML is an important step forward in the global fight against cardiovascular morbidity and mortality, especially in low- and middle-income countries, where the burden of disease is high and limited access to diagnosis and treatment translates into a higher burden of morbidity, mortality, and economic costs.

The Association Between Selected Molecular Biomarkers and Ambulatory Blood Pressure Patterns in African Chronic Kidney Disease and Hypertensive Patients Compared With Normotensive Controls: Protocol for a Longitudinal Study.

BACKGROUND: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. OBJECTIVE: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. METHODS: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. RESULTS: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. CONCLUSIONS: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14820.

Medication adherence and 24-h blood pressure in apparently uncontrolled hypertensive Nigerian patients.

BACKGROUND: Uncontrolled hypertension is a major risk for major cardiovascular events. While medication adherence determines blood pressure (BP) control, studies on treatment adherence among apparently uncontrolled hypertensives are sorely lacking in sub-Saharan Africa. We report the pattern and correlate of medication adherence among the uncontrolled hypertensive population. MATERIALS AND METHODS: We investigated 148 age- and sex-matched hypertensive adults on anti-hypertensive medication for a minimum of 1 year. Apparent uncontrolled BP was defined as clinic BP ≥140/90 mmHg, whereas 24-h ambulatory BP monitoring was used to determine the true uncontrolled hypertension and other BP phenotypes. Using the 8-item Morisky medication adherence scale participants were classified into high, moderate and low adherence while Modified Morisky Scale was used to assess knowledge and motivation. RESULTS: The mean age and BP were 61 ± 13.3 years and 158/91 mmHg, respectively. High adherence was found in 4.1% of the participants while 68.9% and 27% had moderate and low adherence, respectively. A third had true uncontrolled hypertension. A high proportion of the study participants also had a high motivation (68.9%) and knowledge (89.2%). Medication adherence was associated with motivation (P = 0.0001), knowledge (P = 0.002) and obesity (P = 0.036). Knowledge was an independent determinant of medication adherence with no significant effect on BP control. CONCLUSION: High medication adherence was low and a third had true uncontrolled hypertension. Knowledge was an independent predictor of medication adherence with no significant effect on blood control. High medication adherence rather than moderate adherence, and knowledge are indeed needed for adequate BP control.

Knowledge, attitudes and practices related to stroke in Ghana and Nigeria: A SIREN call to action.

INTRODUCTION: Stroke is a prominent cause of death, disability, and dementia in sub-Saharan Africa (SSA). The Stroke Investigative Research and Education Network works collaboratively with stroke survivors and individuals serving as community controls to comprehensively characterize the genomic, sociocultural, economic and behavioral risk factors for stroke in SSA. PURPOSE: In this paper, we aim to: i) explore the attitudes, beliefs, and practices related to stroke in Ghana and Nigeria using the process of qualitative description; and ii) propose actions for future research and community-based participation and education. METHODS: Stroke survivors, their caregivers, health care professionals, and community representatives and faith-based leaders participated in one of twenty-six focus groups, which qualitatively explored community beliefs, attitudes and practices related to stroke in Ghana and Nigeria. Arthur Kleinman's Explanatory Model of Illness and the Social Ecological Model guided the questions and/or thematic analysis of the qualitative data. We hereby describe our focus group methods and analyses of qualitative data, as well as the findings and suggestions for improving stroke outcomes. RESULTS AND DISCUSSION: The major findings illustrate the fears, causes, chief problems, treatment, and recommendations related to stroke through the views of the participants, as well as recommendations for working effectively with the SIREN communities. Findings are compared to SIREN quantitative data and other qualitative studies in Africa. As far as we are aware, this is the first paper to qualitatively explore and contrast community beliefs, attitudes, and practices among stroke survivors and their caregivers, community and faith-based leaders, and health professionals in multiple communities within Nigeria and Ghana.

Development and Reliability of a User-Friendly Multicenter Phenotyping Application for Hemorrhagic and Ischemic Stroke.

BACKGROUND: Annotation and Image Markup on ClearCanvas Enriched Stroke-phenotyping Software (ACCESS) is a novel stand-alone computer software application that allows the creation of simple standardized annotations for reporting brain images of all stroke types. We developed the ACCESS application and determined its inter-rater and intra-rater reliability in the Stroke Investigative Research and Educational Network (SIREN) study to assess its suitability for multicenter studies. METHODS: One hundred randomly selected stroke imaging reports from 5 SIREN sites were re-evaluated by 4 trained independent raters to determine the inter-rater reliability of the ACCESS (version 12.0) software for stroke phenotyping. To determine intra-rater reliability, 6 raters reviewed the same cases previously reported by them after a month of interval. Ischemic stroke was classified using the Oxfordshire Community Stroke Project (OCSP), Trial of Org 10172 in Acute Stroke Treatment (TOAST), and Atherosclerosis, Small-vessel disease, Cardiac source, Other cause (ASCO) protocols, while hemorrhagic stroke was classified using the Structural lesion, Medication, Amyloid angiopathy, Systemic disease, Hypertensive angiopathy and Undetermined (SMASH-U) protocol in ACCESS. Agreement among raters was measured with Cohen's kappa statistics. RESULTS: For primary stroke type, inter-rater agreement was .98 (95% confidence interval [CI], .94-1.00), while intra-rater agreement was 1.00 (95% CI, 1.00). For OCSP subtypes, inter-rater agreement was .97 (95% CI, .92-1.00) for the partial anterior circulation infarcts, .92 (95% CI, .76-1.00) for the total anterior circulation infarcts, and excellent for both lacunar infarcts and posterior circulation infarcts. Intra-rater agreement was .97 (.90-1.00), while inter-rater agreement was .93 (95% CI, .84-1.00) for TOAST subtypes. Inter-rater agreement ranged between .78 (cardioembolic) and .91 (large artery atherosclerotic) for ASCO subtypes and was .80 (95% CI, .56-1.00) for SMASH-U subtypes. CONCLUSION: The ACCESS application facilitates a concordant and reproducible classification of stroke subtypes by multiple investigators, making it suitable for clinical use and multicenter research.

Retinal vascular changes in hypertensive patients in Ibadan, Sub-Saharan Africa.

BACKGROUND: Earlier studies in Nigeria reported the rarity of retinal vascular changes in hypertensives. The aim of this study was to describe the various retinal vascular changes in the hypertensive patients of Nigeria. PATIENTS AND METHODS: Nine hundred and three hypertensive patients were studied. This study was approved by the ethical and research committee of the University of Ibadan and University College Hospital, Ibadan, Nigeria. Blood pressure and anthropometric measurements were measured. Cardiac echocardiography was performed on 156 patients. All patients had dilated fundoscopy and fundus photography using the Kowa portable fundus camera and an Apple iPhone with 20 D lens. Statistical analysis was done with Statistical Packages for the Social Sciences (Version 21). RESULTS: The mean age of patients was 57 years with a male:female ratio of 1. No retinopathy was found in 556 (61.5%) patients. In all, 175 (19.4%) patients had features of hypertensive retinopathy. Retinal vascular occlusion was a significant finding in 121 patients (13.4%), of which branch retinal vein occlusion, 43 (4.7%), and central retinal vein occlusion, 30 (3.3%), were the most prominent ones in cases. Hemicentral retinal vein occlusion, 26 (2.9%), and central retinal artery occlusion, 17 (1.9%), were significant presentations. Other findings included nonarteritic anterior ischemic optic neuropathy in five (0.6%) patients, hypertensive choroidopathy in seven (0.8%) patients, and hemorrhagic choroidal detachment in five (0.6%) patients. Left ventricular (LV) geometry was abnormal in 85 (55.5%) patients. Concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were observed in 43 (27.6%), 26 (17.2%), and 15 (9.7%) patients, respectively. LV hypertrophy was found in 42 (27%) patients, while 60 (39%) patients had increased relative wall thickness. In this study, bivariate analysis showed a correlation between LV relative wall thickness and severity of retinopathy in both eyes (Spearman's coefficient 0.6; P=0.0004). CONCLUSION: Hypertensive retinal vascular changes are not rare in Ibadan.

A 45-year old man with recurrent syncope: an unusual presentation of coronary artery disease.

A 45-year old normotensive, euglycaemic, non-smoker was referred from a peripheral hospital to the Cardiology unit of the University College Hospital, Nigeria for evaluation of recurrent exercise induced syncope. Initial 12-lead electrocardiogram (ECG), 24-hr ambulatory ECG, trans-thoracic echocardiogram and electroencephalogram (EEG) were normal. A repeat episode of syncope warranted further investigation. Immediate post syncope ECG showed deeply inverted symmetrical T waves in the anterior leads. He underwent coronary angiogram which revealed distal left main disease and 70-80% stenosis of the proximal Left Anterior Descending Artery (LAD). The Circumflex artery was non dominant with normal Right Coronary artery. He subsequently had Percutaneous Transluminal Coronary Angioplasty (PTCA) of the LAD. Post-revascularisation course has been satisfactory with no recurrence of syncope. In view of the rising trend of cardiac death in the country, there is the need for high index of suspicion in making diagnosis of coronary artery disease in patients with syncope.