CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 3, July/August 2023 AFRICA 161 reported a history of gestational hypertension had a 9.5-mmHg higher SBP (p < 0.001). Discussion In this study of young black Africans living in urban South Africa, we have shown a high prevalence of EBP, particularly in males, and that an overwhelming proportion who had EBP at 22 years continued to have EBP six years later. In addition, EBP in females was associated with a history of gestational hypertension and injectable contraceptive use, while in males EBP was associated with haematuria. Albuminuria, a surrogate marker for vascular and renal target-organ damage was associated with EBP (in particular, SBP) in males and with SBP in females, with profound implications for premature cardiovascular and all-cause mortality while also providing opportunities for lifestyle and therapeutic interventions to mitigate risk. Our findings suggest that earlier surveillance or screening for hypertension and microalbuminuria in younger population groups could perhaps allow earlier detection of at-risk groups. A review of our contraception policy with a current strong emphasis on the injectable progesterone method as well as follow up of women with gestational hypertension for longer than just six weeks post delivery could also result in at-risk groups being detected prior to long-term hypertensive damage occurring. The BT20 cohort is the longest running birth cohort in sub-Saharan Africa and there are few studies from Africa with which to compare our findings. The Coronary Artery Risk Development in Young Adults (CARDIA) study in the USA showed similar results with 2 277/4 851 (47%) of the cohort developing EBP, stage 1 or stage 2 hypertension, before the age of 40 years. This group was at higher risk for adverse cardiovascular events in later life compared to their normotensive counterparts.9 Factors associated with BP included gender and BMI. Females in our study had lower SBP and DBP, a finding consistent with many other studies and attributable possibly to differences in the developmental programming of BP between men and women, gender-mediated differences in the response to angiotensin II, and differences in sympathetic activation.10-12 It is contrary that females had higher BMIs than males in our study yet a higher BMI was associated with higher SBP and DBP. It is noteworthy that the association with BP was stronger for males despite their lower BMIs overall. Prior studies have shown that at age 17 years, BMI was a strong independent predictor for hypertension in older males aged 30 years, and held true across all BMI categories. In contrast for females, only BMI ≥ 30 kg/m2 or ≥ 95th percentile was associated with elevated risk of hypertension when adjusting for BMI at adulthood.13 The pathogenesis of obesity-related hypertension includes insulin- and leptin-mediated sympathetic nervous system stimulation, renin–angiotensin–aldosterone system (RAAS) activation, increased sodium reabsorption by the kidney by neural, hormonal and renovascular mechanisms and endothelial dysfunction with blunting of physiological vasodilation.14,15 The role of sex hormones, specifically testosterone and oestrogen, and their effects on both weight and BP as well as their effects on the sympathetic nervous system and the RAAS could explain the stronger association with BMI and BP in males.10,16 In those with EBP, albuminuria is recognised as a marker for vascular and endothelial dysfunction and predicts increased risk for cardiovascular and all-cause mortality. Albuminuria is also a marker of glomerular damage and can precede a drop in eGFR. Treating EBP and targeting albuminuria with anti-proteinuric pharmacotherapeutics (such as ACE inhibitors) has been proven to reduce cardiovascular risk, with less impact on preserving kidney function. However, most studies elucidating the risk associated with EBP have been conducted in older cohorts from high-income countries, with few studies from sub-Saharan Africa, especially in young adults.17-20 In the CARDIA study, increased SBP was associated with a higher uACR in midlife.19 Similarly, in a recent study from China examining the effect of BP trajectories from childhood to middle age on renal function, participants with higher levels of SBP in early life had higher uACRs in middle age. In addition, rapid increases in SBP from adolescence to middle age predicted the highest uACRs in middle age.20 In our study, the association between hyperuricaemia and SBP was attenuated in males when adjusting for BMI, but this association persisted in females. Controversy regarding whether the association between hyperuricaemia and BP is cause or effect (or perhaps both), still persists in the literature. Hyperuricaemia in rat models, which resulted in hypertension, showed that these rats developed afferent renal arteriolar vasoconstriction, resulting in renal blood flow reduction, similar to findings in essential hypertension.21,22 This has been postulated to be mediated by endothelial dysfunction and uric acid-induced stimulation of the renin–angiotensin system.21,22 Two meta-analyses have shown a consistent association of uric acid elevation and a higher risk of incident hypertension.23,24 Grayson et al. found that this risk appeared to be more pronounced in females and in younger individuals.23 A 10-year follow up of over 5 000 individuals, with an average age of 38 ± 7 years, found that higher uric acid levels were associated with a higher incidence of hypertension in females (hazard ratio: 1.180; 95% CI: 1.018–1.369) but not in males.25 The reasons for the greater susceptibility in females despite their having lower circulating levels of uric acid are not well understood. The renal handling of uric acid is different in men and women, which seems to be linked to female sex hormones Table 6. Cross-sectional associations with SBP in females at age 28 years Models Beta 95% CI p-value Model 1 (n = 483) BMI Height (cm) Uric acid Urine ACR ≥ 3 mg/mmol (vs < 3 mg/mmol) Model R2 0.3 0.2 22.1 6.3 0.1–0.4 0.0–0.4 4.7–39.5 1.6–11.0 0.004 0.04 0.01 0.008 0.060 Model 1 + contraception use (n = 481) Combined oral contraceptive (vs no contraception) Intra-uterine device Injectables Sterilisation Model R2 0.0 –1.5 4.6 –0.6 –3.9–3.9 –6.6–3.7 2.1–7.2 –14.3–13.2 1.0 0.57 < 0.001 0.93 0.083 Model 1 + gestational hypertension (n = 358) BMI Height (cm) Uric acid Urine ACR ≥ 3 mg/mmol (vs < 3 mg/mmol) Gestational hypertension (vs no gestational hypertension) Model R2 0.1 0.2 20.7 7.6 9.5 –0.1–0.3 0.0–0.4 0.8–40.6 2.5–12.7 6.2–12.8 0.47 0.03 0.04 0.003 < 0.001 0.133 BMI, body mass index; ACR, albumin:creatinine ratio.
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