Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction

Abstract

Objective: To evaluate whether low levels of holotranscobalamin (holoTC) or elevated levels of methylmalonic acid (MMA), both indicators of vitamin B 12 deficiency, might predispose to new cardiovascular events following an acute myocardial infarction (MI). Design: A prospective prognostic study. Setting: One hospital center in Stavanger, Norway. Subjects: A total of 300 patients admitted with an acute MI. Methods: Registration of new TnT positive coronary events (defined as TnT40.05 mg/l and a typical MI pattern) and/or cardiac death during a median follow-up time of 45 months. Results: We compared the recurrence of events in the lowest quartile of holoTC (Q1o73.9 pmol/l) to the event rate above the 25% percentile (Q2-4). For methylmalonic acid (MMA) the same comparison was carried out for the upper quartile (Q4X0.24 mmol/l) as compared with the event rate below the 75% percentile (Q1-3). After 18 and 45 months of follow-up, the odds ratio (OR) for Q1 vs Q2-4 for holoTC was 1.15 (95% confidence interval (CI) 0.91-1.46, P ¼ 0.25) and 1.05 (95% CI 0.86-1.29, P ¼ 0.64), respectively. For MMA the OR for Q4 vs Q1-3 was 0.95 (95% CI 0.76-1.19, P ¼ 0.67) after 18 months and 1.01 (95% CI 0.83-1.23, P ¼ 0.90) after 45 months. Conclusion: This study showed no increased risk of future cardiovascular events associated with low levels of holoTC or high levels of MMA following an acute MI.

Holotranscobalamin is not influenced by decreased renal function in elderly men: the MrOS Sweden study

“…For holoTC, we found a lower reference limit of 19.6 pmol/L, which is in accordance with the manufacturer’s recommendations and some 13,25 but not other 32 studies, probably due to different populations studied. When calculating reference intervals we used exclusion criteria for the healthy subgroup partly based on our previous data, 33 and we used very strict criteria when excluding unhealthy individuals.…”

Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population

“…Compared with healthy controls, patients with myocardial infarction or heart failure had significantly higher MMA concentrations [ 17 , 25 ]. However, among 300 patients with AMI, higher MMA levels were insignificantly associated with adverse outcomes during a 4-year follow-up [ 26 ]. A limited sample size may hinder its power of test.…”

“…MMA-related metabolism occurred in mitochondria, while Hcy metabolized in cytoplasm [ 11 ]. As opposed to the complicated metabolism of Hcy, MMA was not subject to folate or vitamin B6 [ 26 ]. Our findings are of particular interest because the metabolism from MMA to succinate in mitochondria is potentially restorable, and therefore is more suitable to be a potentially modifiable biomarker than Hcy.…”

Effects of a diet containing different sources of omega-3 fatty acids on kidney-related biomarkers in overweight and obese individuals: a randomized clinical trial

“…Another trial in patients with Type 2 diabetes indicated that intake of 4 g of fish oil supplements per day decreased serum creatinine by 0.05 mg/dL after 3 months compared with controls (Wong et al , 2010). In contrast to the trials cited, showing that EPA-DHA may prevent renal failure, some observational studies have found conflicting results (Aarsetoy et al , 2008; Gopinath et al , 2011). However, a finding from one cross-sectional study showed that 100 gr/day of fish consumption was independently associated with preserved kidney function in elderly individuals (Chrysohoou et al , 2013).…”

“…Prior studies have shown that daily fish or walnut meals as part of a weight-reducing regimen have been effective (Bao et al , 1998; Mori et al , 2004; Brennan et al , 2010; Philpott et al , 2019). This might be due to decreased appetite due to omega-3 consumption (Aarsetoy et al , 2008; Albracht-Schulte et al , 2018). Given that our participants were provided a weight loss diet in addition to the omega-3 fatty acid sources and had no renal impairment, our results need to be interpreted with caution.…”