Hyperhomocysteinemia in cardiovascular diseases: revisiting observational studies and clinical trials

[Mito]

Abstract

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.

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials - PubMed

Thromboembolic manifestations are relatively 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 …

pubmed.ncbi.nlm.nih.gov

 

[Zsazsa]

My humble opinion on this subject is that supplementation will help but not much if the (mostly nutritional) causes of HHcy are not reversed.

Conclusions and recommendations
Recent meta-analyses demonstrated a limited but significant beneficial effect of t-Hcy-
lowering RCT on the risk of stroke but no effect on coronary heart diseases. The discordance
between observational studies and RCTs may be explained by the fact that most interventional
studies included CVD patient with baseline t-Hcy levels close to normal values, with excessive
age and too short treatment duration. The discordant results of experimental and observational
studies and RCT have introduced a confusion in clinical practice between the inefficacies of
RCT to prevent CVD by lowering homocysteine in moderate hyper homocysteinemia patients
vs the need to treat CVD patients with causes of intermediate or major HHcy where the medical
benefits are clearly established. Further trials are needed to assess the lowering Hcy effects
according to HHcy categories at baseline. HHcy should be screened in patients with CVD,
especially those without identified risk factors. Furthermore, B12 and folate deficiencies and
inherited disorders of 1-CM should be systematically assessed in patients with
intermediate/major HHcy and CVD outcomes and these patients should be treated according to
current guidelines.

 

[cedric]

Homocysteine stands at the crossroad of metabolic pathways. So it could be low B2, B3, folate, B12, glycine, adenine ( FAD, NAD, SAM-e), low B6 P-5-P, Mg supporting transsulphuration to cysteine, taurine, sulphate. It is just a sign of blockade of methylation or transsulphuration. Homocysteine is dimerised to homocystine like cysteine to cystine or GSH to GS-SG.

 

[Zsazsa]

Homocysteine stands at the crossroad of metabolic pathways. So it could be low B2, B3, folate, B12, glycine, adenine ( FAD, NAD, SAM-e), low B6 P-5-P, Mg supporting transsulphuration to cysteine, taurine, sulphate. It is just a sign of blockade of methylation or transsulphuration. Homocysteine is dimerised to homocystine like cysteine to cystine or GSH to GS-SG.

I observed that supplemental zinc is very helpful.