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Background Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. Methods UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have >= 5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. Expected outcomes The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients. The authors gratefully acknowledge the enthusiasm of the patientsenrolled in UPRIGHT-HTM and the expert assistance of the consul-tants, residents and nursing staff supporting the trial at the clinicalsites. The Alliance for the Promotion of Preventive Medicine is anot-profitresearchinstitute(URL:www.appremed.org;Belgianregis-trationnumber,739849385),whichreceivedanon-bindinggrantfromOMRONHealthcareCo.Ltd.,Kyoto,Japan.UPRIGHT-HTMisaTopZprojectsupportedbyOMRONHealthcareCo.Ltd.,Kyoto,Japan

PhD (Science with Physiology), North-West University, Potchefstroom Campus Motivation - The accurate measurement of blood pressure remains the most essential technique for the diagnosis and management of hypertension. In addition, there is increasing evidence that the measurement of clinic blood pressure may yield incorrect estimates of a patient’s true blood pressure status. This is due to blood pressure fluctuations throughout the day-night period, with reported higher blood pressure during the day and lower at night, reflecting the physiological dipping pattern of night-time blood pressure. Furthermore, studies indicated the occurrence of cardiovascular events such as stroke, myocardial infarction and sudden cardiac death more frequently during the morning hours after waking up, due to increased blood pressure. The morning blood pressure surge (MBPS) is a normal physiological response to changes in the activity of the sympathetic nervous system associated with the process of awakening and other factors (including age, ethnicity, sex, hypertensive status, health behaviours, or dipping status). A MBPS up to 37 mmHg is considered physiological, while an exaggerated MBPS above 37 mmHg is pathological, and associated with cardiovascular events, mainly in hypertensive and elderly individuals. A majority of previous studies focusing on exaggerated MBPS were conducted in elderly and hypertensive individuals, but there is scant knowledge on ethnic differences, prevalence and effects of an exaggerated MBPS on subclinical hypertension-mediated organ damage in young healthy individuals. This study therefore investigated MBPS in young black and white normotensive adults, and the relationships between the MBPS, measures of arterial function and autonomic function in healthy black and white South African men and women, aged between 20 and 30 years. Aim - The overarching aim of this Ph.D. thesis was to obtain a better understanding regarding the MBPS and how it relates to arterial function and subclinical hypertension-mediated organ damage in a healthy bi-ethnic South African population, aged between 20 and 30 years. Methodology - This thesis used data (presented in Chapter 3, 4 and 5) collected from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT). We included the first consecutive 845 black and white men and women in total. Groups were stratified by gender and ethnicity, and dipping status as specified by statistical interaction terms. Cardiovascular measurements included ambulatory blood pressure measurements, MBPS (sleep-trough and dynamic morning surge) and pulse wave velocity. Using fundoscopy, we also included measurements of the microvasculature, namely retinal vessel calibres. As part of ambulatory blood pressure and electrocardiogram monitoring, we measured 24-hour heart rate variability. Baroreceptor sensitivity was determined using the validated cross-correlation baroreflex sensitivity (xBRS) method. Using accelerometery, we were able to measure total energy expenditure and activity energy expenditure. Results and conclusions of each manuscript. The first manuscript (Chapter 3) aimed to determine interactions of sex and black and white ethnicity across increasing quartiles of MBPS. This manuscript also aimed to explore whether differences in cardiovascular-related measures and specific health behaviours exist across increasing MBPS quartiles. We also aimed to determine if an exaggerated MBPS already occurs in young black and white adults. We found an interaction of ethnicity on the relationship between sleep-trough surge with cardiovascular markers and health behaviours (p

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non-validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non-validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country-specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross-checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.

The home blood pressure monitoring (HBPM) method that measures blood pressure during sleep hours was reported to be comparable to ambulatory blood pressure monitoring (ABPM) in measuring nighttime blood pressure and detecting nocturnal hypertension. The aim of this study was to directly compare the prognostic power of nocturnal hypertension detected by HBPM versus ABPM for predicting future cardiovascular events. We analyzed nighttime blood pressure (measured by HBPM and ABPM) data of 1005 participants who were included in the J-HOP study (Japan Morning Surge-Home Blood Pressure). During a follow-up period of 7.6±3.4 years, 80 cardiovascular disease events occurred. The majority (91.8%) of our study population were hypertensive, and 80.7% of participants were using antihypertensive medication. Nighttime home systolic blood pressure (SBP) was higher compared to nighttime ambulatory SBP (123.0±14.6 versus 120.3±14.4 mm Hg, P

M Health Science (Cardiovascular Physiology), North-West University, Potchefstroom Campus Motivation: Stroke is the second leading cause of death worldwide. In South Africa, the stroke incidence and mortality rate increased significantly in the last 30 years. Elevated plasma levels of the multimeric glycoprotein, von Willebrand factor (vWF) are associated with an increased risk of stroke and other cardiovascular diseases. vWF is responsible for inducing platelet adhesion and aggregation at sites of vascular injury, and for the protection of the blood-clotting protein, Factor VIII from proteolysis. vWF is regulated by ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) that cleaves vWF into smaller, less reactive molecules. Previous reports suggest that modifiable lifestyle factors such as physical activity, diet and smoking can contribute to the variation in plasma levels of haemostatic markers. Taking into account the shift towards unhealthy lifestyles in the youth, we investigated the associations between vWF and ADAMTS13 with health behaviours, namely physical activity, alcohol consumption, smoking, obesity, salt intake, and socio-economic status in young black and white adults from South Africa. Methods: This study made use of the baseline data of the African-PREDICT study. We included 602 black and 594 white young adults aged 20-30 years. General Health and Demographic Questionnaires were used to report information on socio-economic status (SES), tobacco use, alcohol intake, and contraceptive use. Anthropometric measurements including weight, height and waist circumference were taken, and body mass index (BMI) was calculated. To determine physical activity, accelerometry was used by means of an ActiHeart monitor. Clinic and 24-hour blood pressure measurements were conducted using standard methods. Fasted citrated blood samples were used for the analysis of vWF:Ag and serum samples were used to measure ADAMTS13, cotinine and gamma-glutamyl transferase (GGT). Twenty four-hour urine samples were used to estimate daily salt intake. Results: Black adults had higher vWF:Ag and lower ADAMTS13 levels compared to whites (all p

Background: The impact of a sedentary and unhealthy lifestyle on cardiovascular health is well documented, however the current obesity and hypertension trends among children is concerning. The ExAMIN Youth SA study aims to investigate the impact of lifestyle behaviors (physical fitness/activity, dietary intake and psychosocial factors) involved in early vascular aging among South African children. Methods: This study is an analytical, multidisciplinary, observational cohort study in a school-based setting. We aim to phenotype a cohort of approximately 1000 primary school children (black and white boys and girls between ages 5–9 years) based on current clinical childhood conditions including hypertension and obesity. The primary phenotype is large artery stiffness and retinal microvascular diameters, both biomarkers of early vascular aging. The risk factors and mediators of early vascular ageing and also responsible for the clinical conditions include physical inactivity, unhealthy diet, and life stress. Additionally, urinalysis and salivary analyses will be performed to identify biomarkers related to the pathophysiology of early vascular aging. Discussion: In line with the growing prevalence of obesity and hypertension responsible for the development of early vascular ageing from childhood to adulthood, this study will address the critical areas in which we observe unfavorable arterial modulation related to dietary behaviors, physical inactivity and early life stress. Implementation of novel biological markers may further contribute to our understanding of early cardiovascular adaptations in childhood, and aid in the development of primary prevention programs. Trial registration: The study was retrospectively registered on ClinicalTrials.gov on 15 August 2019 (NCT04056377).

Background Globally hypertension is stabilising, but in sub-Saharan Africa the incidence of hypertension remains on an increase. Although this might be attributed to poor healthcare and ineffective antihypertensive treatment, there is a limited understanding of population and individual-specific cardiovascular pathophysiology – necessary for effective prevention and treatment strategies in Africa. As there is a lack of longitudinal studies tracking the early pathophysiological development of hypertension in black populations, the African-PREDICT study was initiated. The purpose of this paper is to describe the detailed methodology and baseline cohort profile of the study. Methods and results From 2013 to 2017, the study included 1202 black ( N = 606) and white ( N = 596) men and women (aged 20–30 years) from South Africa – screened to be healthy and clinic normotensive. At baseline, and each 5-year follow-up examination, detailed measures of health behaviours, cardiovascular profile and organ damage are taken. Also, comprehensive biological sampling for the ‘omics’ and biomarkers is performed. Overall, the baseline black and white cohort presented with similar ages, clinic and 24-hour blood pressures, but black adults had lower socioeconomic status and higher central systolic blood pressure than white individuals. Conclusions The prospective African-PREDICT study in young black and white adults will contribute to a clear understanding of early cardiovascular disease development.

The endogenous Na+/K+-ATPase inhibitor, marinobufagenin (MBG), strongly associates with salt intake and a greater left ventricular mass index (LVMi) in humans and was shown to promote cardiac fibrosis and hypertrophy in animals. The adverse effects of MBG on cardiac remodeling may be exacerbated with obesity, due to an increased sensitivity of Na+/K+-ATPase to MBG. This study determined whether MBG is related to the change in LVMi over time in adults with a body mass index (BMI) &ge, 30 kg/m2 (obese) and &lt, 30 kg/m2 (non-obese). The study followed 275 healthy participants (aged 20&ndash, 30 years) from the African-Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) study over 4.5 years. At baseline, we measured 24 h urine MBG excretion. MBG levels were positively associated with salt intake. LVMi was determined by two-dimensional echocardiography at baseline and after &gt, 4.5 years. With multivariate adjusted analyses in obese adults (N = 56), we found a positive association of follow-up LVMi (Adjusted (Adj.) R2 = 0.35, Std. &beta, = 0.311, p = 0.007) and percentage change in LVMi (Adj. R2 = 0.40, = 0.336, p = 0.003) with baseline MBG excretion. No association of LVMi (Adj. R2 = 0.37, p = 0.85) or percentage change in LVMi (Adj. R2 = 0.19, p = 0.68) with MBG excretion was evident in normal weight adults (N = 123). These findings suggest that obese adults may be more sensitive to the adverse cardiac effects of MBG and provide new insight into the potential role of dietary salt, by way of MBG, in the pathogenesis of cardiac remodeling in obese individuals.

Background It is well established that an exaggerated morning blood pressure surge (MBPS) is associated with an increased risk for cardiovascular disease development in hypertensive individuals. However, in non-dipping individuals, a lower surge was reportedly associated with increased cardiovascular risk. Sympathetic nervous system activity is involved in 24-hour blood pressure fluctuations, including night-time dipping and the MBPS. To better understand this interaction, we investigated associations of MBPS with heart-rate variability and baroreceptor sensitivity in young healthy dippers and non-dippers. Methods We included black and white men and women (n = 827), aged 20-30 years and determined the MBPS using two formulas: the sleep-trough and dynamic morning surge. For autonomic function we determined baroreceptor sensitivity and heart-rate variability. Results The majority of non-dippers in this population were black (70.4%), presenting lower sleep-trough and dynamic morning surge (all p < 0.001). Heart-rate variability was comparable between dippers and non-dippers, whereas baroreceptor sensitivity was higher in non-dippers (p = 0.021). Despite a suppressed MBPS profile in non-dippers, we found both sleep-trough (β = −0.25; p = 0.039) and dynamic morning surge (β = −0.14; p = 0.047) to be inversely and independently associated with 24-hour heart-rate variability (total power). These results were absent in dippers. Conclusions In conclusion, we found a higher night-time blood pressure coupled with lower MBPS in young healthy non-dippers. Furthermore, this lower MBPS was independently and negatively associated with autonomic neural activity, suggesting increased autonomic function involvement in MBPS suppression of non-dippers. The predictive value of suppressed nocturnal dipping pattern should be investigated while taking autonomic neural activity into account