Homocysteine, Ischemic Stroke, and Coronary Heart Disease in Hypertensive Patients

Abstract

Stroke is the leading cause of permanent disability in China, 1 and ischemic stroke (IS) accounts for almost 80% of all strokes, 2 whereas coronary heart disease (CHD) is a major worldwide health threat. In tandem with the economic success of China, the number of individuals in China with IS and CHD has increased significantly in recent years, with stroke resulting in 301 million disability-adjusted life-years. 3CHD in Chinese adults aged 35 to 84 years is predicted to increase by 64% during the period 2020-2029. 4 Although numerous epidemiology studies have researched the association between hyperhomocysteinemia and IS or CHD, the results have been conflicting. Most studies have been retrospective and focused on healthy populations in the developed world, whereas data from developing countries remains limited.Vitamins B12 and B6 and folate are involved in the metabolism of methionine, and deficiency of these B vitamins can cause elevation of total homocysteine (tHcy) levels.5 Deficiencies in these nutrients are more prevalent in developing countries. A meta-analysis of randomized trials demonstrated that homocysteine-lowering interventions for stroke seem not to have a significant effect in geographic regions with high dietary folate intake, but may have a substantial effect in regions with low folate intake, such as Asia. 6 Regarding public health guidelines,Background and Purpose-Total homocysteine level (tHcy) is a risk factor of ischemic stroke (IS) and coronary heart disease. However, the results are conflicting and mainly focused on healthy individuals in developed countries. Methods-A prospective, population-based cohort study was conducted among 5935 participants from 60 communities in the city of Shenzhen, China. A Cox regression analysis was applied to evaluate the contribution of tHcy to the risk of IS and coronary heart disease. The effect of folic acid supplementation on tHcy levels was also evaluated among 501 patients with essential hypertension, who received an average of 2.5 years of folic acid supplementation. Results-After adjustment for confounding factors, the hazard ratios (95% confidence intervals) of IS caused by hyperhomocysteinemia were 2.18 (1.65-2.89), 2.40 (1.56-3.67), and 2.73 (1.83-4.08) in the total, male, and female participants, respectively. Compared with normal levels of tHcy (<15 μmol/L), the hazard ratios (95% confidence intervals) for IS in the highest tHcy category (≥30 μmol/L) were 4.96 (3.03-8.12), 6.11 (3.44-10.85), and 1.84 (0.52-6.46) in the total, males, and females participants, respectively. However, we did not observe a significant relationship between tHcy and the risk of coronary heart disease. The 2.5 years of folic acid supplementation reduced tHcy levels by 6.7 μmol/L (27.92%) in patients with essential hypertension. Conclusions-Hyperhomocysteinemia in Chinese hypertensive patients is significantly associated with IS risk but not coronary heart disease susceptibility, and folic acid supplementation can efficiently reduce tHcy levels.

Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT)

“…In China, the prevalence of hyperuricemia is w13% (31), and the prevalence of tHcy concentrations $15 mmol/L is 27-30% (32,33), without the mandatory folic acid fortification of foods. In China, the estimated number of adults with hyperuricemia is 170 million, and the number of adults with tHcy concentrations $15 mmol/L is 350 million.…”

Methylene Tetrahydrofolate Reductase (MTHFR) rs868014 Polymorphism Regulated by miR-1203 Associates with Risk and Short Term Outcome of Ischemic Stroke

“…The A1298C variant results in substitution of glutamate (Glu) to alanine (Ala) at codon 429 in the S-adenosylmethionine regulatory domain of the MTHFR protein [18, 19]. The MTHFR C677T genetic variant can lead to elevated levels of plasma tHcy and, thus, increased ischemic stroke risk [20, 21], data of which have been further confirmed in other studies [12, 13, 22]. tHcy is thought to increase thrombotic risk through induction of endothelial injury in the venous and arterial vasculature [23].…”

“…For example, upregulated tHcy can induce cell apoptosis by increased ROS levels through activation of the p38 MAPK pathway [11]. In the context of stroke, the elevated levels of plasma tHcy were shown to associate with increased risk of ischemic stroke [12, 13]. MTHFR is localized at chromosome 1 p36.3 in the human genome, and to date there are over 40 point mutations or SNPs in the MTHFR gene identified [14].…”

Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

“…Several observational studies have shown that a raised blood Hcy level -hyperhomocysteinemia (HHC) is a risk factor for cardiovascular events, including ischemic heart disease, chronic kidney disease and cerebrovascular disease [2,3].…”

“…Acta Veterinaria-Beograd 2017, 67 (2), [254][255][256][257][258][259][260][261][262][263][264][265][266][267][268][269][270] MNOGOBROJNI MEHANIZMI UKLJUČENI SU U STIMULATORNE EFEKTE HOMOCISTEINA NA GLATKU MUSKULATURU DUODENUMA PACOVA STOJANOVIĆ Marija, ŠĆEPANOVIĆ Ljiljana, MITROVIĆ Dušan, ŠĆEPANOVIĆ Vuk, ŠĆEPANOVIĆ Radomir, DJURIC Marko, ILIĆ Slobodan, ŠĆEPANOVIĆ Teja, DJURIC Dragan Novije studije potvrdile su povezanost hiperhomocisteinemije i gastrointestinalnih oboljenja, mada su i dalje nepoznati direktni efekti homocisteina na gastrointestinalnu reaktivnost. Cilj ovog rada bio je da demonstrira kako homocistein moduliše azot monoksid zavisnu duodenalnu relaksaciju i da li holinergički receptori i K+ kanali imaju uticaja na stimulaciju motiliteta, kao i da ispita da li je oksidativni stres udružen sa efektima homocisteina.…”