From the Guidelines
Relationship Between Homocysteine and Hypertension
There is a significant relationship between homocysteine levels and the risk of atherosclerotic vascular disease, including stroke, but the direct link to hypertension is less clear.
- Elevated levels of plasma homocysteine are associated with a 2- to 3-fold increased risk for atherosclerotic vascular disease, including stroke 1.
- The relationship between homocysteine levels and cardiovascular risk factors, such as systolic blood pressure, is complex and may be influenced by other factors like renal function 1.
- Hyperhomocysteinemia is caused by genetic defects, nutritional deficiencies of pyridoxine (vitamin B6), folic acid, and cobalamin (vitamin B12), or decreased renal clearance of homocysteine in patients with chronic renal failure 1.
- Some studies suggest that lowering homocysteine levels by B-complex vitamin therapy may reduce the risk of stroke, but the evidence is not conclusive, and most studies have found no benefit of homocysteine lowering on clinical cardiovascular end points 1.
- A meta-analysis found a 19% reduction in stroke risk per 25% lower homocysteine concentration after adjustment for smoking, systolic BP, and cholesterol 1.
- Another meta-analysis found that for each 5 μmol/L increase in homocysteine, the odds of stroke increased by 59% 1.
- The pathophysiological mechanism by which homocysteine may be responsible for the observed associations remains unclear, but it is thought to be related to the development of vascular disease and atherosclerosis 1.
From the Research
Relationship Between Homocysteine and Hypertension
- The balance of evidence from observational studies suggests that elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke, but the evidence linking hyperhomocysteinemia with hypertension is limited and inconsistent 2.
- A prospective nested case-control study found that participants who developed hypertension had significantly higher levels of baseline plasma homocysteine than matched controls, with a crude relative risk of 1.56 and a multivariable relative risk of 1.63 3.
- A cross-sectional analysis of prospectively collected data found that homocysteine was significantly associated with hypertension mediated organ damage, including pulse wave velocity, albumin-creatinine ratio, and estimated glomerular filtration rate 4.
- Experimental data suggest that homocysteine may play a role in the pathogenesis of essential hypertension by impairing vascular endothelial and smooth muscle cell function, and that correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid could be a useful adjuvant therapy of hypertension 5.
- A study on white coat hypertension found that plasma homocysteine levels were significantly higher in the white coat hypertension group compared to the controls, and that the increase in homocysteine level in white coat hypertension is not as high as in sustained hypertension 6.
Key Findings
- Elevated homocysteine levels are associated with increased risk of carotid artery disease and stroke 2.
- Homocysteine is an independent risk factor for cardiovascular and cerebrovascular disease 4.
- Homocysteine levels are associated with hypertension mediated organ damage, including pulse wave velocity and albumin-creatinine ratio 4.
- Correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid could be a useful adjuvant therapy of hypertension 5.
- White coat hypertension is associated with high levels of homocysteine, which is a strong risk factor for coronary artery disease 6.
Study Limitations
- The evidence linking hyperhomocysteinemia with hypertension is limited and inconsistent 2.
- Further controlled randomized trials are necessary to establish the efficacy and tolerability of homocysteine-lowering interventions 2, 5.
- The study on white coat hypertension had a small sample size and was limited to a specific population 6.