Methylmalonic acid and vitamin B12 in patients with heart failure

Polytarchou, Kali; Dimitroglou, Yannis; Varvarousis, Dimitrios; Christodoulis, Nikolaos; Psachoulia, Christina; Pantziou, C.; Mourouzis, Iordanis; Pantos, Costas; Manolis, Antonis S

doi:10.1016/j.hjc.2019.10.010

Cited by 20 publications

(23 citation statements)

References 22 publications

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“…In our stratification analysis, a stronger association was identified between MMA (both continuous and categorical forms) and all-cause mortality in participants with B12 ≥ 400 pmol/L, compared with that in those with B12 < 400 pmol/L. Thus, mitochondrial dysfunction and oxidative stress, as well as poor prognosis should be cautious in adults with elevated MMA, especially in those with normal B12 simultaneously [ 17 , 23 ]. Those biological and clinical studies as well as our results support mitochondria-derived metabolite MMA as a promising surrogate biomarker for mitochondrial dysfunction and oxidative stress.…”

Section: Discussionmentioning

confidence: 98%

“…Several cross-sectional studies suggested that MMA was a potential risk factor of CVD, diabetic complications, and dementias. 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 ].…”

Section: Discussionmentioning

confidence: 99%

“…Inborn methylmalonic acidemia causes serious injury in mitochondria-rich organs, including cerebropathy nephropathy and cardiomyopathy in children [ 13 , 15 , 16 ]. Blood MMA may be a favorable candidate marker of mitochondrial dysfunction and oxidative stress to predict adverse outcomes for chronic disease [ 17 ]. Currently, circulating MMA has been used to screen genetic methylmalonic acidemia and Cbl deﬁciency in clinic [ 11 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Liu

et al. 2020

Redox Biology

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Background Inherited methylmalonic acidemia is characterized by mitochondrial dysfunction, oxidative stress, and damage of mitochondria-rich organs in children. It is unclear whether methylmalonic acid (MMA) is related to poor prognosis in adults. The study aims to investigate the associations of MMA with all-cause and cause-specific mortality in the general population. Methods Overall, 23,437 adults from the US National Health and Nutrition Examination Survey (NHANES) were enrolled. NHANES 1999–2004 and 2011–2014 were separately used as primary and validation subsets (median follow-up 13.5 and 2.8 years, respectively). Circulating MMA was measured with gas chromatography/mass spectrophotometry. Hazard ratios (HR) were estimated using weighted Cox regression models. Results During 163,632 person-years of follow-up in NHANES 1999–2004, 3019 deaths occurred. Compared with participants with MMA <120 nmol/L, those with MMA≥250 nmol/L had increased all-cause and cardiovascular mortality in the multivariable-adjusted model [HR(95%CI), 1.62 (1.43–1.84) and 1.66 (1.22–2.27), respectively]. The association was especially significant among participants with normal cobalamin. MMA remained an independent predictor of all-cause mortality occurring whether within 5-year, 5–10 years, or beyond 10-year of follow-up (each p for trend≤0.007). That association was repeatable in NHANES 2011–2014. Moreover, baseline MMA improved reclassiﬁcation for 10-year mortality in patients with cardiovascular disease (net reclassification index 0.239, integrated discrimination improvement 0.022), overmatched established cardiovascular biomarkers C-reactive protein or homocysteine. Conclusions Circulating level of mitochondrial-derived MMA is strongly associated with elevated all-cause and cardiovascular mortality. Our results support MMA as a surrogate biomarker of mitochondrial dysfunction to predict poor prognosis in adults. The biological mechanisms under cardiovascular disease warrant further investigation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang

Liu

et al. 2020

Redox Biology

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“…This is understandable since oxidative stress may accelerate the conversion of homocysteine into glutathione [ 21 ]. In heart failure patients, increased plasma MMA levels are associated with the presence of comorbidities, not with cobalamin levels [ 22 ]. Of patients with cobalamin levels >350 pg/ml, considered sufficient, one third had elevated MMA values (>32 ng/ml).…”

Section: Methylmalonic Acid and Heart Failurementioning

confidence: 99%

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

et al. 2021

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Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies. 1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

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“…Experienced patients often make such adjustments themselves successfully [8,9]. When medications for frequently occurring comorbidities, such as atrial fibrillation, hypertension, and diabetes, are also taken into account, the result is a labyrinthine, ever-changing medication regimen that requires time, presence of mind, and dedication to successfully adhere to [10,11].…”

Section: Introductionmentioning

confidence: 99%

A Patient-Oriented App (ThessHF) to Improve Self-Care Quality in Heart Failure: From Evidence-Based Design to Pilot Study (Preprint)

Bakogiannis¹,

Tsarouchas²,

Mouselimis³

et al. 2020

Preprint

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BACKGROUND Heart failure (HF) remains a major public health challenge, while HF self-care is particularly challenging. Mobile health (mHealth)–based interventions taking advantage of smartphone technology have shown particular promise in increasing the quality of self-care among these patients, and in turn improving the outcomes of their disease. OBJECTIVE The objective of this study was to co-develop with physicians, patients with HF, and their caregivers a patient-oriented mHealth app, perform usability assessment, and investigate its effect on the quality of life of patients with HF and rate of hospitalizations in a pilot study. METHODS The development of an mHealth app (The Hellenic Educational Self-care and Support Heart Failure app [ThessHF app]) was evidence based, including features based on previous clinically tested mHealth interventions and selected by a panel of HF expert physicians and discussed with patients with HF. At the end of alpha development, the app was rated by mHealth experts with the Mobile Application Rating Scale (MARS). The beta version was tested by patients with HF, who rated its design and content by means of the Post-Study System Usability Questionnaire (PSSUQ). Subsequently, a prospective pilot study (THESS-HF [THe Effect of a Specialized Smartphone app on Heart Failure patients’ quality of self-care, quality of life and hospitalization rate]) was performed to investigate the effect of app use on patients with HF over a 3-month follow-up period. The primary endpoint was patients’ quality of life, which was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 5-level EQ-5D version (EQ-5D-5L). The secondary endpoints were the European Heart Failure Self-care Behavior Scale (EHFScBS) score and the hospitalization rate. RESULTS A systematic review of mHealth-based HF interventions and expert panel suggestions yielded 18 separate app features, most of which were incorporated into the ThessHF app. A total of 14 patients and 5 mHealth experts evaluated the app. The results demonstrated a very good user experience (overall PSSUQ score 2.37 [SD 0.63], where 1 is the best, and a median MARS score of 4.55/5). Finally, 30 patients (male: n=26, 87%) participated in the THESS-HF pilot study (mean age 68.7 [SD 12.4] years). A significant increase in the quality of self-care was noted according to the EHFScBS, which increased by 4.4% (SD 7.2%) (P=.002). The mean quality of life increased nonsignificantly after 3 months according to both KCCQ (mean increase 5.8 [SD 15] points, P=.054) and EQ-5D-5L (mean increase 5.6% [SD 15.6%], P=.06) scores. The hospitalization rate for the follow-up duration was 3%. CONCLUSIONS The need for telehealth services and remote self-care management in HF is of vital importance, especially in periods such as the COVID-19 pandemic. We developed a user-friendly mHealth app to promote remote self-care support in HF. In this pilot study, the use of the ThessHF app was associated with an increase in the quality of self-care. A future multicenter study will investigate the effect of the app use on long-term outcomes in patients with HF.

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Methylmalonic acid and vitamin B12 in patients with heart failure

Cited by 20 publications

References 22 publications

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

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

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

A Patient-Oriented App (ThessHF) to Improve Self-Care Quality in Heart Failure: From Evidence-Based Design to Pilot Study (Preprint)

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