L-homoarginine is associated with decreased cardiovascular- and all-cause mortality.

BACKGROUND: Increasing evidence suggests that L-homoarginine, an endogenous analogue of the amino acid L-arginine, may have beneficial effects on vascular homeostasis. We examined whether L-homoarginine is associated with 10-year risk of all-cause and cardiovascular mortality in a black South African population. METHODS: We included 669 black South African participants (mean age 59.5 years), 143 of whom died during the 10-year follow-up period. Mortality data were acquired via verbal autopsy. Plasma L-homoarginine (and other related markers) were analysed with liquid chromatography-tandem mass spectrometry. RESULTS: Survivors had higher L-homoarginine levels compared with nonsurvivors (1.25 µM vs. 0.89 µM; P < .001). Multivariable Cox regression analyses revealed that higher plasma L-homoarginine predicted a reduction in 10-year cardiovascular (hazard ratio [HR] per SD increment, 0.61; 95% CI 0.50 to 0.75) and all-cause (hazard ratio [HR] per SD increment, 0.59; 95% CI 0.41 to 0.84) mortality risk. CONCLUSION: Higher L-homoarginine levels are associated with reduced risk of 10-year cardiovascular and all-cause mortality. Regulation of L-homoarginine levels as a therapeutic target in the management of cardiovascular disease should be investigated.

Homoarginine and blood pressure: a 10-year prospective relationship in normotensives.

Nitric oxide plays a major role in the regulation of blood pressure, and impaired nitric oxide bioavailability contributes to the development of hypertension (HT). Various factors may contribute to nitric oxide bioavailability-including availability of the substrate for nitric oxide synthesis, L-arginine and its homolog L-homoarginine. We investigated whether blood pressure after 10 years associates with baseline L-homoarginine in participants who remained normotensive (NT) or developed HT, respectively. Data from the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North-West Province, were used. We investigated participants who either remained NT (N = 166) or who developed HT (N = 166) over 10 years. Blood pressure was measured with validated OMRON devices and serum L-homoarginine was analyzed with liquid chromatography-tandem mass spectrometry. L-homoarginine levels were similar at baseline (p = 0.39) and follow-up (p = 0.93) between NT and hypertensive groups. In the group that remained NT after 10 years, baseline L-homoarginine correlated positively with follow-up brachial systolic blood pressure (adj.R2 = 0.13; ß = 0.33; p = 0.001), brachial pulse pressure (adj.R2 = 0.15 ß = 0.40; p = 0.001), and central pulse pressure (adj.R2 = 0.20; ß = 0.30; p = 0.003). No significant associations were found in the group that developed HT after 10 years. We found a positive, independent association between blood pressure and L-homoarginine in a group that remained NT, but not in a group that developed HT after 10 years. This may suggest a protective role for L-homoarginine to maintain normal blood pressure, but only to a certain level. Once HT develops other factors may overshadow the protective effects of L-homoarginine.

A demographic approach to assess elevated blood pressure and obesity in prepubescent children: the ExAMIN Youth South Africa study.

BACKGROUND: Obesity and hypertension prevalence among children are a concern, with limited evidence available on sex and ethnic differences in childhood blood pressure. We aimed to determine the number of children with hypertension and obesity to identify unique adiposity and blood pressure characteristics by sex and ethnicity, and to estimate the odds of having elevated blood pressure with increasing adiposity. METHODS: We included 1062 healthy children (5-9 years of age) in an observational school-based study in South Africa. Pediatric validated automated devices were used to measure brachial blood pressure and performed pulse wave analysis to assess central hemodynamics. Standard anthropometry was carried out to determine body composition and demographic questionnaires were completed. RESULTS: Almost 20% of children were overweight/obese and 14.1% had elevated blood pressure or hypertension (22.8%). Ethnic differences included greater adiposity in white compared with black children (all P < 0.0001), but higher DBP and total vascular resistance in black compared with white children (both P < 0.05). DBP and total vascular resistance were also higher in girls than boys (both P < 0.01). A 51-60% increased risk of developing elevated blood pressure was observed for 1SD (standard deviation) increase of sex-specific BMI [1.60 (1.4-1.8); P < 0.0001] and waist/height ratio [1.51 (1.3-1.7); P < 0.0001]. CONCLUSION: Unique sex and ethnic differences in body composition and blood pressure exist in prepubescent children, with overweight/obesity increasing the risk of elevated blood pressure. Our findings support primary prevention strategies to combat the growing burden of hypertension and obesity-related diseases in youth. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov (NCT04056377).

The Exercise, Arterial Modulation and Nutrition in Youth South Africa Study (ExAMIN Youth SA).

Background: The impact of a sedentary and unhealthy lifestyle on cardiovascular health is well-documented, however the current obesity and hypertension trends among children is concerning. The ExAMIN Youth SA study aims to investigate the impact of lifestyle behaviors (physical fitness/activity, dietary intake and psychosocial factors) involved in early vascular aging among South African children. Methods: This study is an analytical, multidisciplinary, observational cohort study in a school-based setting. We aim to phenotype a cohort of ~1,000 primary school children (black and white boys and girls between ages 5-9 years) based on current clinical childhood conditions including hypertension and obesity. The primary phenotype is large artery stiffness and retinal microvascular diameters, both biomarkers of early vascular aging. The risk factors and mediators of early vascular aging and also responsible for the clinical conditions include physical inactivity, unhealthy diet, and life stress. Additionally, urinalysis and salivary analyses will be performed to identify biomarkers related to the pathophysiology of early vascular aging. Discussion: In line with the growing prevalence of obesity and hypertension responsible for the development of early vascular aging from childhood to adulthood, this study will address the critical areas in which we observe unfavorable arterial modulation related to dietary behaviors, physical inactivity, and early life stress. Implementation of novel biological markers may further contribute to our understanding of early cardiovascular adaptations in childhood, and aid in the development of primary prevention programs. Trial registration: The study was retrospectively registered on ClinicalTrials.gov on 15 August 2019 (NCT04056377).

Correction: Morning blood pressure surge in young black and white adults: The African-PREDICT Study.

In the article "Morning blood pressure surge in young black and white adults: The African-PREDICT Study" by Gontse Gratitude Mokwatsi, Aletta Elisabeth Schutte, Catharina Martha Cornelia Mels and Ruan Kruger which appeared in 'Journal of Human Hypertension' (2018) volume 32, DOI 10.1038/s41371-018-0089-3, the authors regret that they mentioned erroneously that none of their study participants had an exaggerated morning blood pressure surge. They would like to point out that 40 participants in their study population had an exaggerated sleep-trough surge whereas 128 had an exaggerated dynamic surge.

Morning blood pressure surge in young black and white adults: The African-PREDICT Study.

An exaggerated morning blood pressure surge (MBPS) has independent predictive value for cardiovascular mortality and is suggested to be prevalent in elderly hypertensive patients: men and white populations. To better understand the MBPS profile in a young and normotensive population, we evaluated the MBPS in young adults and explored associations with demographic, cardiovascular and health behaviour measurements. We included 845 black (n = 439) and white (n = 406) men and women aged between 20 and 30 years. We calculated the sleep-trough and dynamic morning surge, and compared demographic data, health behaviours and ambulatory blood pressure according to MBPS quartiles. In the total group, higher waist circumference, socioeconomic score, lean mass, ambulatory blood pressure (24-h, daytime blood pressure) and increased night-time dipping (all p < 0.05) were found in the highest sleep-trough and dynamic morning surge quartiles. In the total white group, particularly men, both sleep-trough and dynamic morning surge were higher than the black group (all p < 0.013). More black participants were non-dippers than whites (44% vs 34%; p = 0.004). In multivariable adjusted regression in the total group, we found no consistent associations of MBPS with demographic and health behaviour measurements. MBPS related independently and positively with night-time percentage dipping in all ethnic groups (all p < 0.01). Ethnic differences in MBPS is evident in young adults, with a higher, but normal MBPS in white men. A non-dipping night-time pattern in young black adults (with reduced MBPS) and a higher MBPS (observed in dippers) may serve as potential risk factors for cardiovascular disease.

The Association of Endothelin-1 with Markers of Arterial Stiffness in Black South African Women: The SABPA Study.

Background. Limited data exist regarding endothelin-1 (ET-1), a vasoactive contributor in vascular tone, in a population subjected to early vascular deterioration. We compared ET-1 levels and explored its association with markers of arterial stiffness in black and white South Africans. Methodology. This cross-sectional substudy included 195 black (men: n = 99; women: n = 95) and 197 white (men: n = 99; women: n = 98) South Africans. Serum ET-1 levels were measured as well as markers of arterial stiffness (blood pressure, pulse wave velocity, and arterial compliance). ET-1 levels were higher in black men and white women compared to their counterparts after adjusting for C-reactive protein. In both single and partial (adjusting for body mass index and gamma glutamyl transferase) regression analyses ET-1 correlated with age, interleukin-6, high density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and pulse wave velocity in black women. In multivariate regression analyses the independent association of ET-1 with systolic blood pressure (Adj. R (2) = 0.13; ß = 0.28, p < 0.01) and pulse pressure (Adj. R (2) = 0.11; ß = 0.27, p < 0.01) was confirmed in black women only. ET-1 additionally associated with interleukin-6 in black women (p < 0.01). Conclusion. Our result suggests that ET-1 and its link with subclinical arteriosclerosis are potentially driven by low-grade inflammation as depicted by the association with interleukin-6 in the black female cohort.