Morning blood pressure surge and its association with arterial function and subclinical target organ damage in young South Africans : the African-PREDICT study

Abstract

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<0.01). Interaction terms of ethnicity (p<0.001) and sex (p=0.016) on the relationship between dynamic surge with cardiovascular markers and health behaviours were observed. In white men, both sleep-trough and dynamic morning surge were higher than the black group (all p<0.01). A higher proportion of white individuals had an exaggerated sleep-trough (6.16% vs 3.42%; p=0.21) and dynamic morning (15.8% vs 14.6%; p=0.63) surge when compared to the black population. On the other hand, more black participants were non-dippers than whites (44% vs 34%; p=0.004). MBPS related independently and positively with night-time percentage dipping in all ethnic groups (all p<0.01). No consistent independent associations of health behaviours with MBPS were obtained. However, we confirmed ethnic differences in MBPS in young adults, with a higher, but normal MBPS in white men, however, the non-dipping night-time pattern in young black adults may serve as a potential risk factor for future cardiovascular disease. The aim of the second manuscript (Chapter 4) was to explore whether the MBPS is associated with measures of the microvascular structure and macrovascular function in dippers and non-dippers. Dippers had a higher, but normal sleep-trough surge (p<0.001). Measures of microvascular structure (central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)) and macrovascular function (pulse wave velocity) were comparable between dippers and non-dippers. Partial correlations (adjusted for age, sex and ethnicity) indicated a positive association between central retinal artery equivalent and sleep-trough surge (r=0.20; p=0.021) as well as a negative association between central retinal artery equivalent and night-time diastolic blood pressure (r=–0.24; p=0.004) in dippers. Multiple regression analysis confirmed a positive relationship of CRAE with sleep-trough surge (adjusted R2=0.33; β=0.16; p=0.040) in dippers only. These associations were absent in non-dippers. Our results suggest that a normal MBPS, evident in dippers, may play an important role to preserve retinal artery diameter. To better understand the involvement of autonomic function on MBPS in dippers and non-dippers, we also investigated associations of the MBPS with heart rate variability and baroreceptor sensitivity in the African-PREDICT population of young healthy adults, including dippers and non-dippers (Chapter 5). The majority of non-dippers in this population were black individuals (70.4%), with apparent lower sleep-trough and dynamic morning surge (all p<0.001) compared to dippers. Baroreceptor sensitivity was higher in non-dippers (p=0.021), while heart rate variability was comparable between dippers and non-dippers. There was an inverse association of both sleep-trough (β=–0.25; p=0.039) and dynamic morning surge (β=–0.14; p=0.047) with 24-hour heart rate variability (total power) in non-dippers only. This result suggests increased autonomic function involvement in the observed lower MBPS of non-dippers. General conclusion - In this study, ethnic differences in MBPS is evident in young and healthy adults, with a higher proportion of white individuals presented with an exaggerated MBPS. When reviewing factors that relate to MBPS, no associations were found with any health behaviours such as obesity or salt intake, however the positive association of MBPS with night-time blood pressure indicates the important role of dipping status when interpreting MBPS. The positive association between MBPS and the central retinal artery equivalent observed in dippers suggests the important role of normal morning surge (dependent on night-time dipping) in preserving retinal arteriolar diameter of dippers. Apart from the association with the microvasculature, MBPS also related inversely with increased autonomic function in non-dippers. Although non-dippers had a lower MBPS, their blunted night-time blood pressure dipping pattern (in response to increased autonomic function) may increase their risk for future cardiovascular disease and adverse outcomes.