Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes

Stubbs, P J; Al-Obaidi, Mohamed; Conroy, Ronán; MusB,; Collinson, Paul; MRCPath,; Graham, Ian; Frcpi,; Noble, Mark I. M.

doi:10.1161/01.cir.102.6.605

Cited by 102 publications

(74 citation statements)

References 32 publications

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“…3,4 Our data describing a direct positive relation between homocysteine and subsequent vascular events within the AFCAPSA/Tex-CAPS cohort are consistent with most but not all prior studies of homocysteine and vascular risk. [5][6][7][8][9][10][11]17 Particular strengths of the present analysis that we believe increase its validity and generalizability include our large sample size, the use of a validated commercial assay for homocysteine assessment, and clear end point definitions and complete cohort ascertainment.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events

Ridker¹,

Shih²,

Cook³

2002

ACC Current Journal Review

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Background-Elevated homocysteine levels are associated with increased coronary risk, and it has been suggested that homocysteine screening may provide a method to identify high-risk patients for aggressive primary prevention. Methods and Results-Homocysteine was measured at baseline and after 1 year among 5569 participants in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a randomized trial of lovastatin in the primary prevention of acute coronary events. The effects of homocysteine, LDL cholesterol, and lovastatin on risk were assessed over 5.2 years of trial follow-up. Median baseline homocysteine levels were significantly higher among study participants who subsequently had acute coronary events compared with those who did not (12.1 versus 10.9 mol/L, PϽ0.001). The relative risks of future events from lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2 (PϽ0.001). These effects were similar among those allocated to lovastatin and those allocated to placebo and were modestly attenuated after adjustment for other traditional risk factors. As predicted, the subgroup of participants with elevated LDL cholesterol and elevated homocysteine levels were at high risk and benefited greatly from statin therapy (relative risk, 0.46; 95% CI, 0.29 to 0.75; number needed to treatϭ26). However, in contrast to findings in this trial for C-reactive protein, homocysteine evaluation did not help to define low LDL subgroups with different responses to lovastatin therapy. Conclusions-Although homocysteine predicted future coronary events in AFCAPS/TexCAPS, we found little evidence that homocysteine evaluation provided an improved method to target statin therapy among those with low-to-normal LDL cholesterol levels.

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Section: Discussionmentioning

confidence: 98%

“…[9][10][11] Partly on the basis of these observations, homocysteine screening also has been advocated as a method to improve detection of high-risk patients. However, no data are available addressing whether homocysteine evaluation might, like CRP, provide a method to better target statin therapy among those with low-to-normal LDL cholesterol levels.…”

mentioning

confidence: 99%

Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events

Ridker¹,

Shih²,

Cook³

2002

ACC Current Journal Review

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“…The profession does not seem to have caught up with the fact that there are beneficial lipoproteins of high density (HDL). The factors in non-diabetic patients that subsequent events did correlate with were: infarct size (as assessed by troponin [15], previous ACS, insulin resistance [16], plasma homocysteine rose above normal [17] and raised lipoprotein(a) [18]. Of particular interest was the link between raised homocysteins and pro-thrombosis [19].…”

Section: Causative Factors In Patientsmentioning

confidence: 99%

Commentary: On the Pathophysiology of Coronary Heart Disease

Noble¹

2017

J Med Surg Pathol

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This article highlights some important aspects of the pathophysiology of coronary artery disease, namely:• The distribution of lesions within the arterial tree at sites of low wall shear stress.• The potential role of low flow-mediated arterial dilatation at sites of low wall stress.• Low flow-mediated dilatation leads to low nitric oxide production by the arterial endothelium and consequent reduced protection against lesion formation.• Flow-mediated dilatation is reduced by high lumenal glucose concentration.• The role of the glycocalyx dysfunction in mediating flow-mediated dilatation and consequent reduced NO production by the arterial endothelium and cell adhesion.• Stenoses cause convective acceleration of blood velocity and a consequent increase in platelet shear stress.• Increased platelet shear stress activates platelets with release of serotonin.• Serotonin activates more platelet activation via the 5HT 2A platelet receptor causing a positive feedback and thrombus growth.• Arterial thrombus growth is abolished by 5HT 2A receptor antagonists, the key to improved treatment of the disease.• One 5HT 2A receptor antagonist has been shown in humans to be safe and to cause no excess bleeding from wounds.

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“…It was suggested that lowering Hcy levels by 3μmol/L (by increasing folic acid intake) would reduce the risk of CHD by 16%, deep vein thrombosis by 25% and stroke by 24% [95]. Finally, in some studies raised Hcy levels emerged as a strong predictor of adverse clinical outcomes in patients with acute coronary syndromes (ACS) [101][102][103].…”

Section: Hcy and Cvdmentioning

confidence: 99%

Associations of Thrombotic-Hemostatic Factors with Cardiovascular Disease~!2009-10-29~!2009-12-22~!2010-04-08~!

Lioudaki¹,

Ganotakis²

2012

TOCCHEMJ

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Cardiovascular disease (CVD) remains a leading cause of global morbidity and mortality despite identification of major cardiovascular (CV) risk factors and risk reduction via appropriate interventions. During the last years several markers have been studied as potential predictors of CV events. Hemostatic and thrombotic factors such as fibrinogen, homocysteine, factor VII, von Willebrand, tissue plasminogen activator, plasminogen activator inhibitor -1, D-dimer and lipoprotein ( ) have been found to be closely related to CVD. Many epidemiological studies have indicated that raised levels of these factors are associated with higher incidence of CVD, while some others have yielded conflicting results. As a consequence, it remains obscure whether they contribute to prediction of future CV events on top of conventional risk factors. Although data suggest that most of them are somehow implicated in CVD pathophysiology, it is not clearly defined yet whether treatment of abnormal levels leads to CV risk reduction. As a result measurement and treatment of these factors are justified only in exceptional cases. Further investigation is required in order to conclude whether and which of these factors may claim a position in everyday clinical practice.

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Effect of Plasma Homocysteine Concentration on Early and Late Events in Patients With Acute Coronary Syndromes

Abstract: Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

Cited by 102 publications

References 32 publications

Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events

Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events

Commentary: On the Pathophysiology of Coronary Heart Disease

Associations of Thrombotic-Hemostatic Factors with Cardiovascular Disease~!2009-10-29~!2009-12-22~!2010-04-08~!

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