The relationship of pulse pressure and pulse pressure amplification with the reninangiotensin- aldosterone system in young adults : the African-PREDICT study

Abstract

Motivation: There are number of factors that are known to contribute to the elevation of blood pressure (BP) and the subsequent increase in cardiovascular risk. One of the most prominent systems is the renin-angiotensin-aldosterone system (RAAS), which controls electrolyte and fluid volume. Components of the RAAS (prorenin, renin, angiotensinogen, angiotensins, angiotensin-converting enzyme (ACE) and aldosterone) have been linked to cardiac and vascular remodelling and subsequent cardiovascular disorders such as hypertension, atherosclerosis and cardiac hypertrophy. Pulse pressure (PP) has been established as a significant marker of cardiovascular risk. Furthermore, pulse pressure amplification (PPA), the difference between central PP and brachial PP, has in recent years shown the potential to be a risk factor for cardiovascular disease (CVD). It is thus clear that in order to understand the development and progression of hypertension and its associated risk, it is important to recognise that BP varies across the vasculature and this complexity may influence the relation with BP regulating pathways such as the RAAS. Previous studies investigating the associations between hemodynamic factors and the RAAS focused largely on older and highrisk populations. It is therefore unclear whether any adverse associations are already present between the RAAS and PP as well as PPA in young populations. It therefore, becomes imperative to investigate the link between PP and its amplification in young healthy populations in order to broaden understanding and identify possible areas of intervention to prevent the development of cardiovascular disease. Aim: The main aim of this study was to investigate the relationship of PP and its amplification (PPA) with RAAS components including prorenin, renin, aldosterone and ACE in young black and white, men and women. Methods: The study population consisted of 752 participants from the African-PREDICT study. Demographic information was obtained through the general health questionnaire. The following anthropometric measurements were also taken: height, weight, body mass index, waist circumference, weight to height ratio was then subsequently calculated. The ActiHeart device (CamNtech Ltd., England, UK) was used to calculate total energy expenditure (TEE) over a period of 7 days. Brachial blood pressure was measured with the Dinamap Procare 100 Vital signs Monitor (GE Medical Systems, Milwaukee, USA) with GE Critikon latex-free Dura-Cuffs (medium and large). The brachial artery was used on both left and right arms and the measurements were performed in duplicate at 5 minutes intervals. Brachial PP was then calculated by subtracting diastolic BP (DBP) from systolic BP (SBP) using the mean of both the right and left arms. The SphygmoCor XCEL device (SphygmoCor XCEL, AtCor Medical, Sydney, Australia) was used to produce an arterial waveform from which pulse wave analysis was used to obtain central SBP (cSBP) and central PP (cPP). PPA was the classified as bPP/cPP along with these pulse wave velocity (PWV) was also captured at the right carotid and femoral arterial pulse points. Twenty-four-hour BP measurements were also performed (heart rate (HR), DBP, SBP and PP). Masked hypertension was classified as clinical BP measurements within normal limits (<140/90 mm Hg) and 24-hour BP classed as hypertensive (SBP>140 mm Hg and/or a DBP>90 mm Hg). Dipper status was determined according to ambulatory BP with the formula used by American Heart Association. The following concentrations for biological and biochemical variables were determined: Serum creatinine, cotinine, C-reactive protein (CRP), total and high-density lipoprotein cholesterol, glucose and gamma glutamyltransferase (GGT) as well as urinary sodium, potassium and chloride, then the Na/K ratio was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) formula. Serum samples were analysed for total renin, aldosterone as well as ACE. EDTA samples was used for analysis of prorenin. Results: Of the total population, 16.8% were found to have masked hypertension of this, 20.2% were white and 13.6% were black (p=0.02). The white group was older when compared to the black group (p˂0.001). When looking at the RAAS components, the white group showed higher prorenin and aldosterone levels (both p˂0.001), whereas the black group showed higher total renin (p=0.05), eGFR (p˂0.001) and sodium-to-potassium ration (p<0.001). When looking at the cardiovascular measurements; the black group had higher cSBP (p˂0.001) and DBP (p=0.002), on the other hand, the white group had a higher 24-hour SBP and 24-hour PP (both p˂0.001) but a lower heart rate (p˂0.001). No significant differences in PPA were observed. A lower percentage of the black group presented as nocturnal dippers compared to the white group (46.7% vs 64.3.5, p<0.001). Though, the white group had a higher TEE they presented with higher weight, BMI and waist circumference (all p˂0.001) as compared to the black group. The white group also had higher glucose (p˂0.001) and total cholesterol (p=0.001) levels. When comparing the men and women within the black and white group, black men presented with higher office bPP, 24-hour PP, cSBP and cPP (all p≤0.001)) as well as PPA (p=0.007), but a lower 24-hour HR (p<0.001) as compared to black women. White men also had higher bPP and, 24-hour PP, cSBP, cPP and PPA (all p<0.001), but a lower HR (P<0.001). A higher percentage of black men (18.9% vs 10.21%) and white men (35.6% vs 7.92%) had masked hypertension (p=0.02 and p<0.001 respectively) as compared to their female counterparts. When comparing the RAAS components, black women had lower total renin (p<0.001), prorenin (p<0.001) and ACE (p=0.001) levels than the black men. White women had lower renin (p<0.001), prorenin (p=0.005) and eGFR (p=0.006) but had higher aldosterone levels (p<0.001) than black men. In the forward stepwise multiple regression analyses an association between cPP with ACE (β=0.10, p=0.001) was observed only in the total group. A negative association between total renin and bPP (β=-0.20, p=0.05), as well as a positive association between aldosterone and PPA (β=0.18, p<0.001) were observed in black women, whereas in white women only a negative association between ACE and PPA (β=-0.19, p<0.001) was observed. Conclusions: cPP associated positively with ACE in the total group and PPA negatively with ACE in white women. PPA associated positively with aldosterone and negatively with renin in black women. Our results suggest that that at a young age, the RAAS is adversely associated with haemodynamics and this may translate to increased ethnic and gender specific cardiovascular risk later in life