Hyperhomocysteinemia, Vascular Pathology, and Endothelial Dysfunction

C, van Guldener; Cd, Stehouwer

doi:10.1055/s-2000-8472

Cited by 132 publications

(90 citation statements)

References 37 publications

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“…Homocysteine may induce endothelial dysfunction-mediated atheroma progression. 2,34 Alternatively, hyperhomocysteinemia may result in thrombus accretion on the atheromatous plaque, 35 or it may be a risk marker of atherosclerosis rather than being a risk factor or being in the causal pathway for vascular events. 36 The association with neutrophil count suggests a potential inflammatory/infectious role in atherogenesis and stroke risk.…”

Section: Discussionmentioning

confidence: 99%

Aortic Arch Atheroma Progression and Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack

et al. 2007

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Background-It is not known whether progression of aortic arch (AA) atheroma is associated with vascular events in patients with stroke or transient ischemic attack (TIA). Methods and Results-AA atheroma was detected on baseline transesophageal echocardiogram in 167 consecutive patients who had prevalent stroke or TIA. Of these, 125 consented to a follow-up transesophageal echocardiogram at 12 months. Adequate paired AA images were obtained in 117 (78 with strokes, 39 with TIAs), which allowed detailed measurements of plaques. On admission for their index stroke or TIA, patients were assessed for stroke risk factors, stroke subtypes, baseline AA plaque characteristics, and laboratory parameters. Progression of AA atheroma was observed in 33 patients (28%) on 12-month follow-up transesophageal echocardiogram. It was determined that the progression group had significantly higher adjusted homocysteine levels (PϽ0.0001) and neutrophil counts (PϽ0.0001) than the no-progression group. These patients were followed up for a median of 1.7 years from the index stroke/TIA (range 0.5 to 4.5 years) for vascular events including stroke, TIA, myocardial infarction, and death due to vascular causes. Kaplan-Meier curves showed fewer patients with AA atheroma progression remained free of the composite vascular end point (49% compared with 89% in the no-progression group; PϽ0.0001). AA atheroma progression was associated with composite vascular events (hazard ratio 5.8, 95% confidence interval 2.3 to 14.5, Pϭ0.0002) after adjustment for a propensity score based on confounders. Conclusions-In

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Section: Discussionmentioning

confidence: 99%

Aortic Arch Atheroma Progression and Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack

et al. 2007

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“…Thus, we could not determine whether IL-18 or homocysteine was the predominant contributor to increased carotid IMT in type 2 diabetic patients. Although several mechanisms for homocysteine-induced vascular disease have been proposed, including atherogenesis resulting from endothelial dysfunction (35), smooth muscle cell proliferation (36), and hypercoagulation (37), we speculate that inflammation or plaque instability mediated by elevated plasma IL-18 concentration represents a novel mechanism by which hyperhomocysteinemia could accelerate development of atherosclerosis in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Relationships of Plasma Interleukin-18 Concentrations to Hyperhomocysteinemia and Carotid Intimal-Media Wall Thickness in Patients With Type 2 Diabetes

et al. 2003

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OBJECTIVE -We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimalmedia wall thickness (IMT), an early marker of atherosclerosis, in these patients.RESEARCH DESIGN AND METHODS -We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients' plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries.RESULTS -Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 Ϯ 153 vs. 118 Ϯ 37 pg/ml, P Ͻ 0.001). High IL-18 was defined as equaling or exceeding the mean ϩ 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP.CONCLUSIONS -In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening. Diabetes Care 26:2622-2627, 2003P atients with type 2 diabetes have a high incidence of atherosclerosis, which leads to increased morbidity and mortality from coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD) (1-3). Atherosclerosis is a chronic low-grade inflammatory disease (4 -6). Plasma concentrations of several inflammatory markers such as C-reactive protein (CRP) and interleukin (IL)-6 have been linked with future cardiovascular disease (CVD) in a variety of clinical settings (7,8). IL-18 stimulates release of interferon-␥, shows potent activities on inflammatory and vascular cells, and is considered a proinflammatory cytokine (9). Recently, increased expression of IL-18 has been reported in carotid ulcerated atherosclerotic plaques (10), suggesting that IL-18 also plays a role in plaque destabilization. A recent study (11) identified high serum IL-18 concentrations as a strong predictor of death from cardiovascular causes in patients with CAD.Hyperhomocysteinemia has been associated with atherothrombotic vascular diseases such as CAD, stroke, and PVD (12-14). A previous study (15) demonstrated that moderate hyperhomocysteinemia is a stronger risk factor for CVD in patients with type 2 diabetes than in nondiabetic subjects, suggesting a synergistic effect of diabetes with hyperhomocysteinemia that accelerates the development of atherosclerosis. Although homocysteine can exert vascular toxicity via several mechanis...

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“…Thus, hyperhomoc5'tememia it would still have to be determined, as the indicator, of the correction of the low functional vitamin status (31).…”

Section: Discussionmentioning

confidence: 99%

Assessment of Folate Status: Measurement of Homocysteine versus Vitamin B12 and Folate

et al. 2003

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This study was based on 63 subjects (mean age 50 ± 9) including 41 patients with clinical and objective investigational evidence of vascular disease (age 30-66 years) and 22 control subjects (age 26-54 years). Dietary intake of folate was estimated from a food questionnaire of folate (Q.folate). There was no statistically significant difference between controls and patients for dietary folate. Also the plasma folate levcl did did noly slightly differ between the controls and patients (6.68 ± 2.52 ng/mL versus 5.62 +4.16 ng/'mL, not significant). Patients had higher average homocysteine concentrations than control subjects (12.93 ± 8.79 vs 9.07 ± 3.08 ^mol/l, p<0.05). A significant relationship was observed in controls between plasma folate concentrations and the homocysteine levels (rs = -0.538; p<0.01), and the folate questionnaire (rs ^ 0.697; p<0.001). We found in controls significant positive correlation between vitamin B12 and vitamin B6 (rs = 0.475, p<0.05). By contrast, no association v/as found in patients between folate and homocysteine conccntrations and the dietary nutrient intake of folate. On the other hand vitamin B12 is inversely associated with homocysteine (rs ^ -0.333, p<0.05). These data provide further evidence that plasma homocysteine is an independent risk factor for myocardial infraction. Homocysteine is a valuable functional index of micronutrient status and intakes for people, which can assist the development of the public health. In our population, folate was the most important determinant of plasma homocysteine, even in subjects with apparently adequatc nutritional status of this vitamin.

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Hyperhomocysteinemia, Vascular Pathology, and Endothelial Dysfunction

Cited by 132 publications

References 37 publications

Aortic Arch Atheroma Progression and Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack

Aortic Arch Atheroma Progression and Recurrent Vascular Events in Patients With Stroke or Transient Ischemic Attack

Relationships of Plasma Interleukin-18 Concentrations to Hyperhomocysteinemia and Carotid Intimal-Media Wall Thickness in Patients With Type 2 Diabetes

Assessment of Folate Status: Measurement of Homocysteine versus Vitamin B12 and Folate

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