Homocysteine and myocardial infarction

doi:10.1016/0021-9150(88)90147-5

Atherosclerosis

Volume 71, Issues 2–3, June 1988, Pages 227-233

https://doi.org/10.1016/0021-9150(88)90147-5 Get rights and content

Abstract

Five (24%) subjects out of a group of 21 men, 48–58 years old (mean 54), who had suffered their first myocardial infarction (MI) before the age of 55 and with a low risk profile vis-à-vis conventional risk factors in a health screening preceding the MI, had abnormally high total plasma homocysteine values in the fasting state when investigated within 1–7 years (mean 3) after their MI. The patient group was exactly matched with 36 control subjects for sex, age, diastolic blood pressure, smoking, and serum concentrations of cholesterol and triglycerides. Total plasma homocysteine was negatively correlated to both erythrocyte folate and serum vitamin B₁₂, and vitamin concentrations below the median of the normal distribution were found in the five with high plasma homocysteine content, indicating a possible involvement of reduced remethylation of plasma homocysteine to methionine. After methionine loading, in 3 of the patient group (14%) homocysteine levels exceeded mean + 2 SD for controls, which may indicate heterozygosity for homocystinuria. Results are consistent with the hypothesis that a high plasma homocysteine content may be a risk factor for MI.

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The synthesis of fibroblast growth factor 23 is upregulated by homocysteine in UMR106 osteoblast-like cells
2022, Nutrition
Citation Excerpt :
Apart from B vitamin deficiencies, single nucleotide polymorphisms (SNP) that affect enzymes involved in homocysteine metabolism (e.g., methylenetetrahydrofolate reductase [59,60]) may account for hyperhomocysteinemia. Hyperhomocysteinemia is thought to be a cardiovascular risk factor that favors atherosclerosis [52], cardial infarction [61], and stroke [53]. Moreover, inflammatory diseases, including rheumatoid arthritis [62], and neurodegenerative diseases (e.g., Parkinson's or Alzheimer's disease [63]) are associated with high serum levels of homocysteine [64].
Fibroblast growth factor 23 (FGF23) controls the production and degradation of biologically active vitamin D, 1,25(OH)₂D₃, and phosphate reabsorption in the kidney as a hormone synthesized by bone cells. Additional paracrine effects in other organs exist as well. As a biomarker, the FGF23 plasma concentration increases in renal and cardiovascular diseases, and is correlated with outcome. The regulation of FGF23 is incompletely understood and dependent on several factors, including oxidative stress. L-homocysteine is an amino acid produced in methionine metabolism, and can be converted into further metabolites depending on the availability of vitamin B. Hyperhomocysteinemia is a potential cardiovascular risk factor. Our study aimed to explore whether homocysteine impacts FGF23 synthesis.
Experiments were performed in UMR106 osteoblast-like cells. Fgf23 gene expression and FGF23 protein concentration were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Oxidative stress was determined by 2’,7’-dichlorofluorescein diacetate fluorescence.
Homocysteine dose-dependently upregulated Fgf23 gene expression and protein synthesis. Moreover, homocysteine imposed oxidative stress on UMR106 cells. The effect of homocysteine on Fgf23 was abrogated by antioxidant ascorbic acid.
Homocysteine is a potent stimulator of FGF23 production, an effect at least in part mediated by oxidative stress. The homocysteine-dependent upregulation of FGF23 presumably contributes to its role as a cardiovascular risk factor.
Cardiovascular manifestations of intermediate and major hyperhomocysteinemia due to vitamin B12 and folate deficiency and/or inherited disorders of one-carbon metabolism: A 3.5-year retrospective cross-sectional study of consecutive patients
2021, American Journal of Clinical Nutrition
The association of moderate hyperhomocysteinemia (HHcy) (15–30 μmol/L) with cardiovascular diseases (CVD) has been challenged by the lack of benefit of vitamin supplementation to lowering homocysteine. Consequently, the results of interventional studies have confused the debate regarding the management of patients with intermediate/severe HHcy.
We sought to evaluate the association of intermediate (30–100 μmol/L) and severe (>100 μmol/L) HHcy related to vitamin deficiencies and/or inherited disorders with CVD outcomes.
We performed a retrospective cross-sectional study on consecutive patients who underwent a homocysteine assay in a French University Regional Hospital Center. Patients with CVD outcomes were assessed for vitamin B12, folate, Hcy, methylmalonic acid, and next-generation clinical exome sequencing.
We evaluated 165 patients hospitalized for thromboembolic and other cardiovascular (CV) manifestations among 1006 patients consecutively recruited. Among them, 84% (138/165) had Hcy >30 μmol/L, 27% Hcy >50 μmol/L (44/165) and 3% Hcy >100 μmol/L (5/165). HHcy was related to vitamin B12 and/or folate deficiency in 55% (87/165), mutations in one or more genes of one-carbon and/or vitamin B12 metabolisms in 11% (19/165), and severe renal failure in 15% (21/141) of the studied patients. HHcy was the single vascular risk retrieved in almost 9% (15/165) of patients. Sixty % (101/165) of patients received a supplementation to treat HHcy, with a significant decrease in median Hcy from 41 to 17 µmol/L (IQR: 33.6–60.4 compared with 12.1–28). No recurrence of thromboembolic manifestations was observed after supplementation and antithrombotic treatment of patients who had HHcy as a single risk, after ∼4 y of follow-up.
The high frequency of intermediate/severe HHcy differs from the frequent moderate HHcy reported in previous observational studies of patients with pre-existing CVD. Our study points out the importance of diagnosing and treating nutritional deficiencies and inherited disorders to reverse intermediate/severe HHcy associated with CVD outcomes.
Novel advances in shotgun lipidomics for biology and medicine
2016, Progress in Lipid Research
Citation Excerpt :
However, the analysis with the improved methodology has demonstrated the significant remodeling of fatty acyl chains in these lipid classes with a reduction of the levels of 16:1 FA and increases in the amounts of 18:2, 18:1, and 18:0 FA chains in diabetic mouse liver [138]. A couple of laboratories have believed that enhancing ionization efficiencies of molecular species of different GPL classes could better analyze the species of these lipid classes to reduce ion suppression of the lipid classes present in low abundance by those co-existing in high abundance in shotgun lipidomics [139,140]. Moreover, it is natural that enhancement of ionization efficiencies of the lipid classes of interest definitely yields much broader linear dynamic range through increases in the low limits of detection.
The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms.
Risk Factors for Cardiovascular Disease and Arterial Thrombosis
2007, Consultative Hemostasis and Thrombosis
Predictors of coronary artery disease in the Lebanese population
2006, Thrombosis Research
Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the world. The disease is determined by many risk factors such as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum levels of lipoprotein (a) (Lp(a)), homocysteine, C-reactive protein (CRP) and uric acid. In this study, we evaluated the association of biologic and metabolic parameters with CAD in a group of Lebanese patients.
Three hundred patients were recruited for the study. Biologic and blood metabolic parameters were measured. Patients were then divided into 3 groups according to their catheterization result: 0% stenosis (controls), < 50% stenosis and ≥ 50% stenosis.
Hyperlipidemias, CRP, homocysteine and uric acid levels in CAD patients were not different from those of the controls. However, age, elevated fasting blood glucose (FBG) and elevated serum Lp(a) levels were found to be strong independent predictors of CAD in our study population. Association with CAD was also shown for gender, hypertension, diabetes and family history of CAD.
We report the importance of serum Lp(a) levels and FBG in the prediction and prevention of CAD in our population.
Hyperhomocysteinemia and the development of chronic kidney disease in a general population: The Hisayama study
2004, American Journal of Kidney Diseases
Background: Hyperhomocysteinemia has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. Methods: To clarify this issue, we followed up 1,477 community-dwelling individuals without CKD, aged 40 years or older, for 5 years and examined the effects of baseline serum total homocysteine (tHcy) levels on the development of CKD. Results: During follow-up, 88 subjects experienced CKD. Baseline tHcy levels were greater in men than women (1.35 versus 1.04 mg/L [10.0 versus 7.7 μmol/L]; P < 0.01). Age-adjusted 5-year incidences were 2.2% in the low tertile, 5.4% in the middle tertile, and 8.6% in the high tertile of tHcy levels for men and 3.3%, 6.0%, and 6.9% for women, respectively. The difference between the low and high tertiles was statistically significant for both sexes (P < 0.05). In multivariate analysis, these relationships remained substantially unchanged, even after adjustment for other confounding factors, such as systolic blood pressure, antihypertensive medication, hemoglobin A_1c level, total cholesterol level, high-density lipoprotein cholesterol level, habitual smoker status, regular alcohol intake, proteinuria, and baseline kidney function (odds ratio [OR] in the high tertile of tHcy levels, 2.09; 95% confidence interval [CI], 0.66 to 6.61 for men; OR, 2.86; 95% CI, 1.10 to 7.43 for women). Furthermore, baseline tHcy level showed a significantly inverse association with rate of change in kidney function during the 5 years after being adjusted for confounding factors, including baseline kidney function. Conclusion: Our findings suggest that elevated serum tHcy levels are a significant risk factor for the development of CKD in the general population.

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Research paperHomocysteine and myocardial infarction

Abstract

J. Am. Coll. Cardiol.

J. Am. Coll. Card.

Metabolism

Metabolism

J. Nutr.

Metabolism

Family history of heart attack as an independent predictor of death due to cardiovascular disease

Circulation

Family history of myocardial infarction as an independent risk factor for coronary heart disease

Br. Heart. J.

Disorders of transsulfuration

Heterozygosity for homocysteinuria in premature peripheral and cerebral occlusive arterial disease

N. Engl. J. Med.

Research paper
Homocysteine and myocardial infarction