Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease

Abstract

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007–0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.

Walking Training Improves Systemic and Local Pathophysiological Processes in Intermittent Claudication

“…Increased NO bioavailability may improve endothelial function, blood flow and vasodilatory capacity 22 , contributing to increase walking capacity, mobility and independent living. As endothelial dysfunction 47 , oxidative stress 48 and inflammation 21 are associated with morbimortality and disease progression in IC, their improvement may reduce cardiovascular risk and ameliorate prognosis. Thus, the present study provided novel evidence (systemic and local) about the benefic effects of a submaximal WT on key factors associated with PAD progression and cardiovascular risk (a complete hypothetic model can be seen in graphical abstract).…”

Plasma Levels of Homocysteine is Associated with Liver Fibrosis in Health Check-Up Population

“…Homocysteine (Hcy), a metabolic by-product of methionine, is an essential amino acid derived from dietary protein. 1 High levels of Hcy or hyperhomocysteinemia (HHcy) increases the risk of heart and vascular diseases, 2 as well as other pathological conditions, such as encephalopathy, kidney disease, and liver disease. 3 , 4 Previous studies have shown that Hcy results in increased collagen synthesis and deposition in animal hearts, kidneys, and carotid arteries.…”

Hyperhomocysteinemia: How Does it Affect the Development of Cardiovascular Disease?

“…This mutation leads to loss of more than 60% of MTHFR enzymatic activity [20], and 8% of general population is homozygous for this variant. In these patients, folate level interferes directly with plasma homocysteine content, and this is only increased when folate concentration is below 15.4 nmol/L [27][28][29][30]. This mutation can be present together with the CBS mutation.…”

“…It is more common in men (21% above women) and increases in women during menopause [28]. There is also an increase with age and, since elderly patients show bigger vitamin deficiency, hyperhomocysteinemia is, in this group of individuals, an important risk factor for coronary disease [29,30]. individuals, ranging from 5 to 15 µmol/L [2,12,13].…”