Determinants of day-night difference in blood pressure in subjects of African ancestry

Hypertension is a major risk factor for cardiovascular disease in both developed and developing countries. Blood pressure normally decreases at night and a number of studies have indicated that a reduced nocturnal decline in blood pressure (BP) increases the risk for cardiovascular disease. Nocturnal decreases in BP are attenuated in subjects of African as compared to European descent, but the mechanisms of this effect require clarity. In the present study I attempted to identify potentially modifiable factors that contribute toward nocturnal decreases in BP in a random sample of 171 nuclear families comprising 438 black South Africans living in Soweto. Prior studies have suggested that adiposity and salt intake may determine nocturnal decreases in BP. Adiposity and salt intake were considered to be potentially important factors to consider in the present study as 67% of the group studied were either overweight or obese and in 291 subjects that had complete 24-hour urine collections (used to assess salt intake) and BP measurements, Na+ and K+ intake was noted to be considerably higher and lower respectively than the recommended daily allowance in the majority of people. Moreover, a lack of relationship between either hypertension awareness and treatment and Na+ and K+ intake suggested that current recommendations for a reduced Na+ intake and increased K+ intake in hypertensives do not translate into clinical practice in this community. In order to assess whether adiposity or salt intake are associated with nocturnal decreases in BP in this community, ambulatory BP monitoring was performed using Spacelabs model 90207 oscillometric monitors. Of the 438 subjects recruited, 314 had ambulatory BP measurements that met pre-specified quality criteria (more than 20 hours of recordings and more than 10 and 5 readings for the computation of daytime and nighttime means respectively). To identify whether adiposity or salt intake are associated with a reduced nocturnal decline in BP, non-linear regression analysis was employed with indices of adiposity and urinary Na+ and K+ excretion rates and urine Na+: K+ ratios included in the regression model with adjustments for potential confounders. Neither body mass index, skin-fold thickness, waist circumference, waist-to hip ratio, urinary Na+ and K+ excretion rates, nor urine Na+: K+ ratios were associated with nocturnal decreases in systolic and diastolic BP. Indices of adiposity were however associated with 24 hour ambulatory systolic and diastolic BP. Unexpectedly, female gender was associated with an attenuated nocturnal decrease in BP. In conclusion, in the first random, community-based sample with large sample sizes conducted with ambulatory BP monitoring in Africa, I found that neither adiposity nor salt intake are associated with a reduced nocturnal decline in BP. The lack of association between either salt intake or adiposity and nocturnal decreases in BP was despite a high prevalence of excessive adiposity in the community, as well as clear evidence that current recommendations for a reduced Na+ intake and increased K+ intake do not translate into clinical practice in this community. Thus, based on this study, the question arises as to whether primordial prevention programs targeting excess adiposity or inappropriate salt intake are likely to modify nocturnal decreases in BP, in urban, developing communities of African ancestry in South Africa. However, unexpectedly I noted that females were more likely to have an attenuated nocturnal decrease in BP. Thus further work is required to explain this finding

Nurse versus ambulatory blood pressure measurement in a community of African descent: prevalence and significant of ``white coat`` responses.

Hypertension is a major cause of morbidity and mortality in communities of African ancestry. The most appropriate method of predicting the risk for blood pressure (BP)-related cardiovascular events is through 24-hour ambulatory BP (ABP) monitoring. Although the cost of monitors precludes the use of 24-hour BP measurement in groups of African descent in Africa, the extent to which BP-related cardiovascular risk may be underestimated by nurse-derived clinic BP measurements, and the current method of BP-related risk assessment in these communities, is uncertain. In this regard, nursederived BP measurement is thought to be superior to other forms of in-office BP measurement. Ambulatory 24-hour, day and night BP (SpaceLabs, model 90207) and nursederived clinic BP (CBP) (mean of 5 values) control rates were determined in 689 randomly selected participants (>16 years) of African ancestry in South Africa. Of the participants 45.7% were hypertensive and 22.6% were receiving antihypertensive medication. More participants had uncontrolled BP at night (34.0%) than during the day (22.6%, p<0.0001). However, uncontrolled CBP was noted in 37.2% of participants, while a much lower proportion had uncontrolled ABP (24.1%)(p<0.0001). These differences were accounted for by a high prevalence of isolated increases in CBP (whitecoat effects)(39.4%). Thus, in communities of African descent, despite a worse BP control at night than during the day, a high prevalence of white-coat effects translates into a striking underestimation of BP control when employing CBP rather than ABP measurements. Nurse-derived BP measurements are often as closely associated with organ damage as ABP. However, the extent to which relationships between nurse-derived BP measurements and organ damage reflect a white-coat effect (isolated increase in inoffice BP) as opposed to the adverse effects of BP per se are unknown. In 750 participants from a community sample, target organ changes were determined from carotid-femoral pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software) (n=662) and left ventricular mass indexed to height2.7 (LVMI) (echocardiography)(n=463). Nurse-derived CBP was associated with organ changes independent of 24-hour BP (LVMI; partial r=0.15, p<0.005, PWV; partial r=0.21, p<0.0001) and day BP. However, in both unadjusted (p<0.0001 for both) and multivariate adjusted models (including adjustments for 24-hour BP)(LVMI; partial r=0.14, p<0.01, PWV; partial r=0.21, p<0.0001) nurse office-day SBP (an index of isolated increases in in-office BP) was associated with target organ changes independent of ambulatory BP and additional confounders. Thus, nurse-elicited whitecoat effects account for a significant proportion of the relationship between nursederived CBP and target organ changes independent of ambulatory BP. Therefore, high quality nurse-derived BP measurements do not approximate the impact of BP effects per se on cardiovascular damage. In 750 participants from a community sample I evaluated whether nurse officeday BP is inversely related to day-night BP (BP dipping) and whether this relationship may in-part explain the independent association between office-day BP and organ damage. Nurse office-day systolic BP (SBP) was correlated with % night/day SBP (r=0.22, p<0.0001) and night SBP (r=0.14, p=0.0001). Although unadjusted and multivariate adjusted (including for day SBP) nurse office-day SBP was associated with LVMI (partial r=0.15, p<0.01) and PWV (partial r=0.22, p<0.0001), neither day-night SBP (LVMI; partial r=-0.01, p=0.88, PWV: partial r=-0.04, p=0.30) nor % night/day SBP (LVMI; partial r=0.01, p=0.91, PWV: partial r=0.04, p=0.37) were independently related to target organ changes. Moreover, the relationships between nurse office-day SBP and target organ changes persisted with adjustments for either day-night SBP (p<0.05- p<0.0001) or night SBP (p<0.01-p=0.0001). Thus, although nurse office-day SBP, an index of an alerting response, is independently associated with an atttenuation of nocturnal decreases in SBP, neither a decreased BP dipping, nor nocturnal BP explain the independent relationship between nurse office-day SBP and target organ changes. Whether nurse office-day BP is affected by antihypertensive therapy, is uncertain. In the present study the effect of antihypertensive therapy on nurse office-day BP was assessed in 173 patients whom, off treatment, had a daytime diastolic BP ranging from 90 to 114 mm Hg. Over the treatment period marked decreases in BP occurred (p<0.0001). However, neither nurse office-day systolic (baseline=16.5±15.8 mm Hg, 4 months=15.3±18.9 mm Hg, p=0.49), nor diastolic (baseline=0.9±9.3 mm Hg, 4 months=4.3±10.7 mm Hg, p<0.005) BP decreased significantly from baseline. Thus, despite producing marked decreases in nurse-derived in-office and out-of-office ambulatory BP, antihypertensive therapy produces no change in nurse-elicited isolated increases in in-office BP (white coat-effects) in a group of African descent. In conclusion, the results of the present thesis indicate that in an urban, developing community of African descent, as compared to 24-hour BP measurements, nurse-derived BP measurements elicit a significant in-office increase in BP which translates into a marked underestimation of BP control at a community level; is strongly associated with organ damage through effects that cannot be attributed to 24-hour BP or to relationships with an attenuated decline in nocturnal BP; and which cannot be treated with antihypertensive therapy. Further work is required to assess the most cost-effective approach to excluding nurse-elicited isolated increases in in-office BP before initiating antihypertensive therapy to groups of African descent