Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile

Donner, Markus G.; Klein, Gernot; Mathes, P.; Schwandt, P.; Richter, Werner

doi:10.1016/s0026-0495(98)90256-6

Cited by 36 publications

(15 citation statements)

References 44 publications

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“…Donner, et al 30) have found that in low risk patient groups and patients under the age of 50 the incidence of HHcy was not significantly high. They concluded that the CAD and HHcy relationship reported in other studies was actually a result of other primary risk factors.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Hyperhomocysteinemia on the Presence, Extent, and Severity of Coronary Artery Disease

et al. 2003

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SUMMARYMost cross-sectional and case-control studies indicate that an increased plasma total homocysteine (tHcy) level is an independent risk factor for coronary artery disease (CAD). However, this is still a controversial issue. Recently, it was reported that the level of tHcy is related to the extent and severity of CAD. This study was designed to investigate the relationship between plasma tHcy levels and the presence, extent, and severity of CAD.Three hundred and forty-one patients who underwent coronary angiography were included in the study. Of these patients, 195 had CAD and 146 had normal coronary arteries (control group). The mean tHcy level was found to be higher in patients with significant CAD (16.4 ± 7.4µmol/L vs 13.2 ± 3.6 µmol/L, P < 0.001). This group also had a higher rate of hyperhomocysteinemia (HHcy) (22.6% vs 5.5%, P < 0.001). There were positive relationships between tHcy levels and male gender (P = 0.03, r = 0.16), smoking (P < 0.001, r = 0.19), hyperlipidemia (P = 0.006, r = 0.15), and hypertension (P < 0.001, r = 0.20). Using regression analysis HHcy was determined to be an independent risk factor for CAD (OR = 3.69, CI 95% 1.51-9.06, P = 0.004). However, HHcy was not an independent risk factor in patients with low cardiovascular risk profiles. There was no relationship between the level of tHcy and the severity, extent, and vessel scores of CAD. On the other hand, age and diabetes mellitus were related with all scores of CAD.In conclusion, although hyperhomocysteinemia is an independent risk factor for CAD in our region, it appears to be unrelated to the extent and severity of the disease. (Jpn Heart J 2003; 44: 357-368)

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Section: Discussionmentioning

confidence: 99%

The Effects of Hyperhomocysteinemia on the Presence, Extent, and Severity of Coronary Artery Disease

et al. 2003

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“…This case-control study of 750 CVD patients and 800 control subjects showed that hyperhomocysteinemia had a more than multiplicative effect on risk in smokers and hypertensive subjects and also enhanced the risk conferred by elevated cholesterol. A strong effect modification of the tHcy-CVD association by conventional risk factors may also explain the recent observation that plasma tHcy is not related to coronary heart disease in patients without conventional risk factors such as hypertension, diabetes, and hyperlipidemia (45).…”

Section: Studies In Childrenmentioning

confidence: 96%

The controversy over homocysteine and cardiovascular risk

Ueland

Refsum

Beresford

et al. 2000

The American Journal of Clinical Nutrition

452

237

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Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria, the relation between tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the relation between tHcy in children and CVD in their parents or relatives, and reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B vitamins. Plausible mechanisms include the in vivo interference with nitric oxide-dependent reactive vasodilatation. Some observations have raised questions about tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no relation between tHcy and CVD. 2) Several traditional risk factors are associated with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4) The C677T transition of the methylenetetrahydrofolate reductase gene causes a moderate increase in tHcy but no or only minor increased CVD risk. However, the strength of some of these arguments can be questioned because there is increasing evidence that tHcy is a proximate risk factor provoking the acute event, it strongly interacts with traditional risk factors, and it may predict CVD or death in patients with chronic renal failure. Furthermore, the studies of the C677T polymorphism lack statistical power, and the TT genotype may even modulate CVD risk independently of homocysteine. Thus, only placebocontrolled intervention studies with tHcy-lowering B vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor. Am J Clin Nutr 2000;72:324-32.KEY WORDS Homocysteine, cardiovascular disease, methylenetetrahydrofolate reductase polymorphism, renal, nephrosclerosis INTRODUCTIONPatients with the inborn metabolic error homocystinuria have markedly elevated homocysteine concentrations in plasma and urine and occlusive vascular disease in early adulthood or even in childhood (1). On the basis of these observations, McCully (2) formulated the homocysteine theory of atherosclerosis in 1969 (2). In 1976, Wilcken and Wilcken (3) published their pioneering work on abnormal homocysteine metabolism in patients with coronary artery disease. Since then, convincing evidence has been gathered on the relation between moderate elevation of plasma total homocysteine (tHcy) and the risk of occlusive vascular disease in the coronary, cerebral (4), and peripheral arteries and, more recently, of venous thrombosis (5-7). The literature on this subject now includes > 120 articles reporting on > 12 000 patient-control subject sets. Almost all of the retrospective case-control studies and most of the prospective studies support the concept of hyperhomocysteinemia as a risk factor for cardiovascular disease (CVD; 6, 8), and several meta-analyses showed similar, consistent results, as summarized in Figure 1.Some observations may s...

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“…It has been reported that plasma GSH concentrations remain at mM levels in healthy humans. 32,33) It has been also demonstrated that arsenic concentrations in the plasma of chronic arsenic poisoning patients is at the mM level. 34) Therefore, large amounts of cytotoxic MMAs III DG and DMAs III G are probably not produced nonenzymatically at in vivo levels of arsenicals and GSH.…”

Section: Mmasmentioning

confidence: 99%

Cytolethality of Glutathione Conjugates with Monomethylarsenic or Dimethylarsenic Compounds

Kojima

Sakurai

Waalkes

et al. 2005

Biological & Pharmaceutical Bulletin

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Arsenic is a metalloid element that is widely distributed in the environment as a natural component of soil and in water as inorganic trivalent (arsenite) or pentavalent (arsenate) forms, 1) and its toxicity has been known since ancient times. In Asia and the Americas, chronic arsenic poisoning has occurred as a result of the consumption of high levels of arsenic-contaminated well water. Epidemiological studies have provided clear evidence that inorganic arsenicals are a human carcinogen with target sites including liver, skin, lung, kidney and urinary bladder.2) However, the mechanism of arsenic-induced impediment is not clear. On the other hand, inorganic arsenite has emerged as a potent chemotherapeutic agent with remarkable efficacy for certain human cancers, such as acute promyelocytic leukemia.3,4) It would thus appear that environmental and iatrogenic exposure to arsenic will continue to be common.In humans and numerous experimental animals, pentavalent arsenate is rapidly reduced to trivalent arsenite. 5) Subsequently, it is enzymatically methylated into organic arsenicals, such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ).6) MMAs V and DMAs V are the major organic pentavalent arsenic metabolites in human urine after exposure to inorganic arsenicals. 5,6) It is believed that methylation of inorganic arsenicals results in a reduction in general toxicity, as indicated by their increased in vivo lethal dose in 50% of a population (LD 50 ) and in vitro lethal concentration in 50% of a population (LC 50 ). 7,8) However, recent studies have increasingly suggested that the methylation of inorganic arsenicals is not a universal detoxification mechanism. Some researchers have reported that trivalent methyl arsenicals, such as monomethylarsonous acid (MMAs III ) and dimethylarsinous acid (DMAs III ), were found in urine collected from people who had been exposed to high concentrations of inorganic arsenicals, 9,10) and that synthetic trivalent methyl arsenicals, such as monomethylarsine oxide (MMAs III O) and iododimethylarsine (DMAs III I), are more cytotoxic in vitro than inorganic arsenicals and pentavalent methyl arsenicals.11) Trivalent methyl arsenicals are thought to be generated as arsenical-glutathione conjugates, such as mono-methylarsonous diglutathione (MMAs III DG) and dimethylarsinous glutathione (DMAs III G), in the human body. [12][13][14] It was also reported that reduced glutathione (GSH) nonenzymatically reduces pentavalent methyl arsenicals to trivalent methyl arsenicals in water, thus resulting in the formation of MMAs III DG and DMAs III G in vitro.

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Plasma total homocysteine levels in patients with early-onset coronary heart disease and a low cardiovascular risk profile

Cited by 36 publications

References 44 publications

The Effects of Hyperhomocysteinemia on the Presence, Extent, and Severity of Coronary Artery Disease

The Effects of Hyperhomocysteinemia on the Presence, Extent, and Severity of Coronary Artery Disease

The controversy over homocysteine and cardiovascular risk

Cytolethality of Glutathione Conjugates with Monomethylarsenic or Dimethylarsenic Compounds

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