Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women

Aday, Aaron W.; Duran, Edward K.; Denburgh, Martin Van; Kim, Eun-Jung; Christen, William G.; Manson, Jo Ann E.; Ridker, Paul M.; Pradhan, Aruna D.

doi:10.1161/atvbaha.121.316397

Cited by 20 publications

(19 citation statements)

References 45 publications

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“…A very large prospective observational study of two populations of women observed a dose-dependent risk association with unprovoked pulmonary embolism and deep vein thrombosis with t-Hcy levels. 54 A significant P-for trend was observed for the mortality risk of patients with coronary artery disease according to HHcy stratified in 4 categories, <9.0, 9.0 -14.9, 15.0 -19.9 and >20.0 µmol/L. 55 A large prospective study conducted in China showed hazard ratios of 1.66 (1.18-2.33) and 4.96 (95%CI 3.03-8.12) for ischemic stroke with moderate and intermediate/major t-Hcy compared to normal t-Hcy, respectively (Figure 2).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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Thromboembolic manifestations are relativement frequent in patients with intermediate/severe hyperhomocysteinemia (> 30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15- 30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice. Lowering homocysteine trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half cases and related to B12 and/or folate deficiency and Addisson/Biermer disease in 55% of these cases. In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for vitamin B deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the lowering homocysteine effect according to hyperhomocysteinemia categories at baseline.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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“…Although retrospective studies have at times been conflicting, two large cohorts have shown an association between high homocysteine levels and VTE. 12 Other recent research has demonstrated higher than normal levels in symptomatic AIP patients and those receiving haemin or givosiran. 13 Homocysteine is not collected as part of routine thrombophilia screening at Wellington Hospital and although elevated in case 2, the level was only measured following multiple haem infusions and the prescription of givosiran; hence, it is unclear whether the level was raised prior to the development of VTE or the administration of these agents.…”

Section: Discussionmentioning

confidence: 97%

“…Although retrospective studies have at times been conflicting, two large cohorts have shown an association between high homocysteine levels and VTE 12 . Other recent research has demonstrated higher than normal levels in symptomatic AIP patients and those receiving haemin or givosiran 13 .…”

Section: Discussionmentioning

confidence: 99%

High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria

et al. 2022

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Hereditary coproporphyria (HCP) is the rarest of the autosomal dominant acute porphyrias with an estimated incidence of 0.02 per 10 million per year. HCP has been considered to be mild in presentation compared with the more common acute intermittent porphyria although there is limited information comparing the subtypes. Penetrance in the acute porphyrias is low with 90% of patients with a mutation never exhibiting symptoms. We present seven members from a family with HCP with a novel mutation in whom penetrance and severity are high. In addition, they appear to have a high rate of veno‐thromboembolism. Penetrance is confirmed at 57% but is suspected to be 71%. The first patient experienced life‐threatening complications, four of the seven have had recurrent attacks and the development of opioid dependence has complicated management. The case series documents the impact of a new mRNA interference molecule givosiran as well as a plan for embryo selection which is not commonly used in porphyria. The use of ketamine for the treatment of acute attacks is also documented for the first time in the porphyria literature. The use of international registries would aid the characterisation and management of this very rare disease.

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“…The most common theory is that MTHFR may provoke a hypercoagulable state by causing homocysteinemia, but research findings regarding this have been inconsistent as well [6]. Some data suggest that homocysteine does in fact cause a prothrombotic state, while other articles suggest that elevated homocysteine only indicates increased cardiovascular risk [4,9] and lowering homocysteine levels does not decrease the risk of venous thrombosis [9]. Furthermore, research that does support hyperhomocysteinemia increasing hypercoagulability has not discovered a precise mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…One possible etiology or risk factor was found to be a previous diagnosis of methylenetetrahydrofolate reductase (MTHFR) polymorphism. Studies have shown that the MTHFR polymorphism can result in reduced activity of methylenetetrahydrofolate reductase resulting in hyperhomocysteinemia [3], and elevated homocysteine may result in a prothrombotic state or serve as a marker for cardiovascular risk [4]. Several studies have hypothesized different mechanisms for the potential prothrombotic state that can result from hyperhomocysteinemia [5].…”

Section: Introductionmentioning

confidence: 99%

A Case of Portal Vein Thrombosis in a Patient With Methylenetetrahydrofolate Reductase A1298C Polymorphism

Martin¹,

Struble²,

Prado³

et al. 2022

Cureus

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Portal vein thrombosis (PVT) is a prothrombotic state caused by blood flow stasis, vascular injury, and/or hypercoagulability, resulting in partial or complete occlusion of the portal vein. PVT is a rare diagnosis, particularly among those without liver disease. Typical risk factors for PVT include cirrhosis, hepatocellular carcinoma, myeloproliferative neoplasms, other malignancies, oral contraceptive use, bowel infections, and inherited hypercoagulable disorders. The goal of this study is to analyze a case of PVT in a patient in which no clear etiology could be identified and to evaluate whether the patient's methylenetetrahydrofolate reductase (MTHFR) polymorphism may have been a risk factor. This is a case of a 44-year-old female with a history of irritable bowel syndrome, hypertension, hyperlipidemia, sleep apnea, gastric bypass surgery, and MTHFR polymorphism who presented to a walk-in clinic with five days of severe abdominal pain associated with diarrhea, nausea, and anorexia. Hypertension and tenderness over the right lower quadrant prompted a referral to the emergency department for evaluation of possible appendicitis. A contrasted computerized tomography (CT) scan of the abdomen and pelvis revealed a normal appendix and acute portal vein thrombosis. She was then admitted for treatment with intravenous (IV) heparin, fluids, and pain management. After an uneventful three-day hospital course, the patient was discharged on rivaroxaban with a plan to continue anticoagulation therapy for six months and follow up with a hematologist, who later confirmed the patient did not have any inherited hypercoagulable disorders.It is unclear whether the patient's MTHFR polymorphism prompted her PVT as existing data on MTHFR's effects are limited and conflicting. One cannot conclude that MTHFR caused a state of hyperhomocysteinemia to prompt hypercoagulability, as this has not been consistently proven in current literature, and the patient's homocysteine levels were not measured at the time of diagnosis. This case illustrates that further research on the various MTHFR polymorphisms and their effects on coagulation, potentially via homocysteinemia, is warranted. Further research on the MTHFR polymorphisms may help determine whether providers should test for MTHFR in the evaluation of thrombotic risk factors and may help optimize the treatment of thrombotic events for affected individuals.

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Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women

Cited by 20 publications

References 45 publications

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria

A Case of Portal Vein Thrombosis in a Patient With Methylenetetrahydrofolate Reductase A1298C Polymorphism

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