August 23, 2011 (Detroit, Michigan) — The addition of homocysteine levels to standard cardiovascular risk-assessment criteria significantly boosted their power to predict coronary heart disease events in two broad community-based cohorts of US adults [1].
The predictive power of the biomarker plus Framingham risk scores and C-reactive protein (CRP) levels was especially pronounced among, and often reclassified the risk status of, participants who would otherwise have been marked as being at intermediate CV risk, report the authors, led by Dr Vikas Veeranna (Wayne State University, Detroit, MI).
The post hoc analysis of 6450 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 6797 adults in the third National Health and Nutrition Examination Survey (NHANES 3) was published in the August 30, 2011 issue of the Journal of the American College of Cardiology.
In separate analyses for both cohorts, hazard ratios for major CV end points were determined for homocysteine as both a continuous and categorical variable. Researchers controlled for demographics, body-mass index, systolic blood pressure, smoking, HDL cholesterol, total cholesterol, lipid-modifying therapies, diabetes, antihypertensive therapy, and CRP.
MESA: Hazard Ratio of Homocysteine Measurements for Major CV Events
All CVD events were defined as MI, resuscitated cardiac arrest, confirmed angina, probable angina (if followed by revascularization), stroke, stroke death, CHD death, other atherosclerotic death, and other CVD death; hard CHD events were defined as MI, resuscitated cardiac arrest, or CHD death
The addition of homocysteine levels to Framingham risk score significantly reclassified the CV risk status of 12.9% of MESA participants and 18.3% of those in NHANES 3; the corresponding figures when counting only "intermediate-risk" participants were 21.2% and 19.2%, respectively.
NHANES 3: Hazard Ratio of Homocysteine Measurements for Major CV Events
CVD death was defined as due to ischemic heart disease, cerebrovascular disease, or atherosclerotic heart disease; CHD death was defined as due to ischemic heart disease only
A "net reclassification improvement index" (NRI) score was determined for the two populations to gauge the effect of adding of homocysteine to the Framingham criteria. Adding the biomarker led to significant reclassification by that analysis, as well: an NRI of 0.35 (95% CI 0.17–0.53; p<0.001) in MESA and of 0.57 (95% CI 0.43–0.71; p<0.001) in NHANES 3.
"This study provides a sound rationale for adding homocysteine in CVD risk assessment," write Dr Arduino A Mangoni (University of Aberdeen, Scotland) and Dr Richard J Woodman (Flinders University, Adelaide, Australia) in an accompanying editorial [2]. But it should be interpreted cautiously, they note.
They further observe that no major randomized trial has found that homocysteine-lowering therapies have a major impact on outcomes. Yet "virtually all such trials have been conducted in patients with advanced atherosclerosis (ie, either preexisting CVD or very high risk)."
The editorialists continue, "If homocysteine is to be used as a screening tool in primary prevention, it is imperative that further trials are conducted in low- and intermediate-risk patients without previous CVD. Only then can the real value of measuring homocysteine as a nontraditional CVD risk factor or risk marker be quantified."
The MESA trial was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the MESA study investigators. The authors had no relevant disclosures. Mangoni and Woodman report that they have no relevant disclosures.
The predictive power of the biomarker plus Framingham risk scores and C-reactive protein (CRP) levels was especially pronounced among, and often reclassified the risk status of, participants who would otherwise have been marked as being at intermediate CV risk, report the authors, led by Dr Vikas Veeranna (Wayne State University, Detroit, MI).
The post hoc analysis of 6450 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 6797 adults in the third National Health and Nutrition Examination Survey (NHANES 3) was published in the August 30, 2011 issue of the Journal of the American College of Cardiology.
In separate analyses for both cohorts, hazard ratios for major CV end points were determined for homocysteine as both a continuous and categorical variable. Researchers controlled for demographics, body-mass index, systolic blood pressure, smoking, HDL cholesterol, total cholesterol, lipid-modifying therapies, diabetes, antihypertensive therapy, and CRP.
MESA: Hazard Ratio of Homocysteine Measurements for Major CV Events
| End point | HR (95% CI | p |
| HR per 0.1 log-unit increase in homocysteine level | ||
| All CVD events | 1.87 (1.29–2.69) | <0.001 |
| Hard CHD events | 2.90 (1.69–4.95) | <0.001 |
| HR for homocysteine >15 µmol/L vs <15 µmol/L | ||
| All CVD events | 1.79 (1.19–1.95) | 0.006 |
| Hard CHD events | 2.22 (1.20–4.09) | 0.01 |
The addition of homocysteine levels to Framingham risk score significantly reclassified the CV risk status of 12.9% of MESA participants and 18.3% of those in NHANES 3; the corresponding figures when counting only "intermediate-risk" participants were 21.2% and 19.2%, respectively.
NHANES 3: Hazard Ratio of Homocysteine Measurements for Major CV Events
| End point | HR (95% CI | p |
| HR per 0.1 log-unit increase in homocysteine level | ||
| CVD deaths | 1.97 (1.52–2.55) | <0.001 |
| CHD deaths | 1.95 (1.43–2.64) | <0.001 |
| HR for homocysteine >15 µmol/L vs <15 µmol/L | ||
| CVD deaths | 2.72 (2.01–3.68) | <0.001 |
| CHD deaths | 2.61 (1.83–3.73) | <0.001 |
A "net reclassification improvement index" (NRI) score was determined for the two populations to gauge the effect of adding of homocysteine to the Framingham criteria. Adding the biomarker led to significant reclassification by that analysis, as well: an NRI of 0.35 (95% CI 0.17–0.53; p<0.001) in MESA and of 0.57 (95% CI 0.43–0.71; p<0.001) in NHANES 3.
"This study provides a sound rationale for adding homocysteine in CVD risk assessment," write Dr Arduino A Mangoni (University of Aberdeen, Scotland) and Dr Richard J Woodman (Flinders University, Adelaide, Australia) in an accompanying editorial [2]. But it should be interpreted cautiously, they note.
They further observe that no major randomized trial has found that homocysteine-lowering therapies have a major impact on outcomes. Yet "virtually all such trials have been conducted in patients with advanced atherosclerosis (ie, either preexisting CVD or very high risk)."
The editorialists continue, "If homocysteine is to be used as a screening tool in primary prevention, it is imperative that further trials are conducted in low- and intermediate-risk patients without previous CVD. Only then can the real value of measuring homocysteine as a nontraditional CVD risk factor or risk marker be quantified."
The MESA trial was conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the MESA study investigators. The authors had no relevant disclosures. Mangoni and Woodman report that they have no relevant disclosures.
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