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.

The usefulness of γ-glutamyltransferase as a marker of cardiovascular function in Africans and Caucasians: the SABPA study.

AIM: Serum γ-glutamyltransferase (GGT) is increasingly regarded as a marker of vascular function. However, the usefulness of this marker is in dispute. Gender and ethnic differences, as well as the serum level range where correlations with vascular function will emerge, may complicate the usefulness of GGT. The aim is to compare correlations with markers of vascular function between African and Caucasian groups. METHODS: This cross-sectional target population study involved four groups of African and Caucasian men and women of 100 participants each. Fasting lipids, GGT, C-reactive protein (CRP), reactive oxygen species, and glycosylated hemoglobin (HbA1c) were determined as well as blood pressure, carotid intima-media thickness (CIMT), and left ventricular hypertrophy. RESULTS: γ-Glutamyltransferase levels were significantly higher in Africans compared with Caucasians and also higher in men than in women. γ-Glutamyltransferase correlated with triglycerides in all four groups and after adjusting the correlations sustained in the male groups but disappeared in women. Correlations existed between GGT and blood pressure, except for the African women. After adjustments, CIMT correlated with GGT in Caucasian men (r = 0.29; P < .01). Glycosylated hemoglobin was associated with GGT in Caucasian women (r = 0.26; P = .01) as well as CRP (r = 0.36; P < .01). When the groups were divided into low and high GGT groups by median split, most of the correlations disappeared in the high GGT groups. CONCLUSIONS: Gender and ethnic-specific associations occurred regarding GGT and variables associated with cardiovascular function. With high levels of GGT the correlations diminished. The usefulness of GGT as a marker of vascular dysfunction seems limited.

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.