Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS).
ABSTRACT Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study.
Prospective follow-up study of nonfatal and fatal myocardial infarction through linkage with Swedish hospital discharge and Swedish mortality registers.
Measurements of lipoprotein components from health check-ups in the larger Stockholm area.
The AMORIS subjects (n = 149 121) free of AMI at blood sampling were followed from 1985 to 2002 with respect to n = 6794 first cases of AMI.
Hazard ratios of nonfatal and fatal AMI by lipoprotein parameters were highly significant and about equally strong in both genders. Apolipoprotein B (apoB), nonhigh density cholesterol and low density cholesterol predicted nonfatal AMI (NFAMI) better than fatal AMI, but high density cholesterol or apolipoprotein A-1 did not. Atherogenic components were weaker predictors after 1997 than before. In multivariate analyses apoB/apoA-1 was a better predictor than TC/HDL-C. ApoB/apoA-1 added clinically significant information to TC/HDL-C in men as reflected by a net reclassification improvement (NRI) of 9.4% (P < 0.0001).
ApoB, apoB/apoA-1 and non-HDL-C were found about equally predictive with LDL-C being slightly less, but multivariate analyses showed apoB/apoA-1 to be the strongest predictor. Attenuation of prediction ability between nonfatal and fatal AMI may be due to modern treatment of CHD after a NFAMI and attenuation of hazard ratios after 1997 may be due to selection of lower risk subjects surviving to 1997.
- SourceAvailable from: Gorm Boje Jensen[show abstract] [hide abstract]
ABSTRACT: Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events than low-density lipoprotein cholesterol. We studied 9231 asymptomatic women and men from the Danish general population followed prospectively for 8 years and observed the following incident events: ischemic heart disease 591, myocardial infarction 278, ischemic cerebrovascular disease 313, ischemic stroke 229, and any ischemic cardiovascular event 807. Women with apoB in the upper versus the lower tertile had hazard ratios for ischemic heart disease of 1.8 (1.2 to 2.5), for myocardial infarction 2.6 (1.4 to 4.7), and for any ischemic cardiovascular event 1.8 (1.3 to 2.3), and men had hazard ratios for ischemic heart disease of 1.9 (1.5 to 2.6), for myocardial infarction 2.4 (1.5 to 3.6), and for any ischemic cardiovascular event 1.6 (1.3 to 2.1). Women had similar hazard ratios for ischemic cerebrovascular disease and ischemic stroke. ApoB had a higher predictive ability than low-density lipoprotein cholesterol in the prediction of ischemic heart disease, myocardial infarction, any ischemic cardiovascular event, and any nonfatal ischemic cardiovascular event in both genders (P=0.03 to <0.001). Finally, in smokers older than 60 years with systolic blood pressure >160 mm Hg, apoB contributed 11% in women and 15% in men to the increase in absolute 10-year risk from the lower to the upper apoB tertile. ApoB predicts ischemic cardiovascular events in both genders, and is better than low-density lipoprotein cholesterol in this respect. We suggest that prediction of future ischemic cardiovascular events could be improved by measuring apoB.Arteriosclerosis Thrombosis and Vascular Biology 04/2007; 27(3):661-70. · 6.34 Impact Factor
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ABSTRACT: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449). Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups. In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.Trial Registration ClinicalTrials.gov Identifier: NCT00159835.JAMA The Journal of the American Medical Association 11/2005; 294(19):2437-45. · 29.98 Impact Factor
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ABSTRACT: The objective of this analysis was to demonstrate the frequency and extent of error that results from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to estimate the lipoprotein-related risk of vascular disease within 94,667 men and 75,675 women in the Apoprotein-related Mortality Risk (AMORIS) cohort. The odds ratio (OR) for the risk of fatal myocardial infarction was determined for 1 SD change in the apoB/apoA-I ratio and all the conventional cholesterol ratios--TC/HDL C ratio, LDL C/HDL C ratio, non-HDL C/HDL C ratio. In both men and women, the apoB/apoA-I ratio was significantly greater than any of the cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA-I ratio was taken as the most accurate index of the lipoprotein-related risk of vascular disease. Using Receiver Operating Characteristic analysis, it was demonstrated that the diagnostic accuracy of the apoB/apoA-I ratio was significantly greater than any cholesterol ratio in those with an LDL cholesterol <3.6 mmol L(-1) compared to those with an LDL cholesterol >3.6 mmol L(-1). Indeed, the difference between the apoB/apoA-I OR compared with the TC/HDL C OR progressively widened as risk increased. This suggests that the advantage of the apoB/apoA-I ratio is greatest in the population at highest risk. The distribution of subjects by quintiles showed in both genders that whilst agreement was greatest at the extremes, even at these points there was substantial discordance between the TC/HDL C and the apoB/apoA-I ratios. Within the middle of the distribution, less than 50% of the values were concordant. Finally, when comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male subjects and overestimated risk in 26.1% of male subjects, whereas in the female subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios rather than the apoB/apoA-I ratio results in frequent and substantial error in the estimation of the lipoprotein-related risk of vascular disease.Journal of Internal Medicine 05/2006; 259(5):455-61. · 6.46 Impact Factor