H-Type Hypertension among Black South Africans and the Relationship between Homocysteine, Its Genetic Determinants and Estimates of Vascular Function

Jacomina P du Plessis; Leandi Lammertyn; Aletta E Schutte; Cornelie Nienaber-Rousseau

doi:10.3390/jcdd9120447

H-Type Hypertension among Black South Africans and the Relationship between Homocysteine, Its Genetic Determinants and Estimates of Vascular Function

J Cardiovasc Dev Dis. 2022 Dec 9;9(12):447. doi: 10.3390/jcdd9120447.

Authors

Jacomina P du Plessis¹, Leandi Lammertyn^{2

3}, Aletta E Schutte^{2

3

4}, Cornelie Nienaber-Rousseau^{1

3}

Affiliations

¹ Centre of Excellence for Nutrition, North-West University, Potchefstroom 2520, South Africa.
² Hypertension in Africa Research Team, North-West University, Potchefstroom 2520, South Africa.
³ Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom Campus, Potchefstroom 2520, South Africa.
⁴ School of Population Health, University of New South Wales, The George Institute of Global Health, Sydney, NSW 2000, Australia.

Abstract

Elevated homocysteine (Hcy) increases cardiovascular disease (CVD) risk. Our objective was to emphasize Hcy’s contribution in hypertension and CVD management by determining H-type hypertension (hypertension with Hcy ≥ 10 µmol/L) and associations between Hcy, blood pressure (BP) and estimates of vascular function among Black South Africans. We included 1995 adults (63% female). Plasma Hcy and cardiovascular measures (systolic and diastolic BP (SBP, DBP), pulse pressure, heart rate (HR), carotid-radialis pulse wave velocity (cr-PWV), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1) were quantified. Five Hcy-related polymorphisms (cystathionine β-synthase (CBS 844ins68, T833C, G9276A); methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (MTR A2756G)) were genotyped. Hcy was >10 µmol/L in 41% (n = 762), and of the 47% (n = 951) hypertensives, 45% (n = 425) presented with H-type. Hcy was higher in hypertensives vs. normotensives (9.86 vs. 8.78 µmol/L, p < 0.0001, effect size 0.56) and correlated positively with SBP, DBP, cr-PWV and ICAM-1 (r > 0.19, p < 0.0001). Over Hcy quartiles, SBP, DBP, HR, cr-PWV and ICAM-1 increased progressively (all p-trends ≤ 0.001). In multiple regression models, Hcy contributed to the variance of SBP, DBP, HR, cr-PWV and ICAM-1. H-type hypertensives also had the lowest MTHFR 677 CC frequency (p = 0.03). Hcy is positively and independently associated with markers of vascular function and raised BP.

Keywords: H-type hypertension; MTHFR C677T; blood pressure management; endothelial function; endothelial structure; hyperhomocysteinemia; sub-Saharan Africa; vascular inflammation.

Grants and funding

This research was supported partially by grants from South Africa—Netherlands Research Programme on Alternatives in Development, the South African National Research Foundation, NWU, PHRI, the South African Medical Research Council (SAMRC) and the North West Province Health Department. The authors thank the SAMRC for the scholarship provided to J.P.d.P. through its Division of Research Capacity Development under the National Health Scholarship Program from funding received from the Public Health Enhancement Fund/South African National Department of Health. Disclosure Statement: The funders had no role in the study design, the data collection or analysis, the decision to publish or the preparation of the manuscript, whose content is the sole responsibility of the authors and does not necessarily represent the official views of the funding agencies.