Value of HDL Cholesterol, Apolipoprotein A-I, Lipoprotein A-I, and Lipoprotein A-I/A-II in Prediction of Coronary Heart Disease: The PRIME Study (original) (raw)
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Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study
Atherosclerosis, 2002
The association of an elevated level of lipoprotein (a) (Lp(a)) with the development of coronary heart disease (CHD) remains controversial. Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. In addition, its possible interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.
Apolipoprotein(a) isoforms and coronary heart disease in men A nested case-control study
Atherosclerosis, 1997
The objective of the present study was to examine the possible associations between low molecular weight (LMW) apolipoprotein(a) (apo(a)) isoforms (F,B,S1,S2) and coronary heart disease (CHD). We conducted a nested case-control (prospective) study of five cohorts of white men: The 1936 cohort (baseline 1976, n= 548) and four cohorts from MONICA I born in 1923 (n=463), 1933 (n= 491), 1943 (n =504) and 1953 (n=448) studied at baseline in 1983. At follow up in 1991, 52 subjects had developed a first myocardial infarction and 22 had been hospitalized with angina pectoris. Plasma samples obtained at baseline were stored frozen until 1993-94, when case samples (n= 74) were analyzed together with samples from matched (disease free) controls (n=190). In a statistical model (conditional logistic regression) including all age groups, cholesterol (or apo B) level (PB0.01), systolic blood pressure (P=0.05) and smoking (P =0.02) predicted CHD. In the statistical model Lp(a) interacted significantly with age (OR= 5.7; 95% CI: 1.4-23.6; P= 0.016), and high Lp(a) (over 45 mg/dl) was associated with significantly increased risk in subjects under 60 years (OR= 3.82; 95% CI: 1.47-9.96), but not in older men (OR= 0.67; 95% CI: 0.235-1.89). Therefore, we studied the impact of Lp(a)/apo(a) and other variables in subjects who had been under 60 years when they became cases. Among the younger subjects the presence of LMW apo(a) isoforms significantly predicted the development of CHD (OR=3.83; 95% CI: 1.18-12.4). The increased risk pertained to high Lp(a) (above versus below 45 mg/dl: OR = 3.68; 95% CI: 1.03-13.10), and to Lp(a) concentrations when entered into the model as a continuous variable (P =0.04). Cholesterol or apo B (PB 0.01), smoking (P=0.02), systolic blood pressure (P = 0.05) and low alcohol consumption (under nine drinks/week) (P=0.04) were also significant predictors of CHD. We conclude that LMW apo(a) isoforms are significantly associated with increased risk of CHD in men under 60 years.
Clinical Chemistry, 2004
[apo(a)] size polymorphism. This study was designed to examine the ability of baseline Lp(a) concentration and apo(a) size to predict future severe angina pectoris in apparently healthy men. Methods: Baseline Lp(a) concentration and apo(a) size were determined in 195 men who subsequently developed angina and in 195 men who remained free of cardiovascular disease for 5 years. Results: Cases had higher median Lp(a) concentrations than did controls (30.6 vs 22.5 nmol/L; P ؍ 0.02). Lp(a) concentration was predictive of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0, 1.8, and 2.6; P for trend ؍ 0.015]. The increased risk was ϳ4-fold (95% confidence interval, 1.4-to 11-fold) among men who had Lp(a) above the 95th percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95% confidence interval, 1.5-to 43-fold). Small apo(a) size isoforms also significantly predicted risk of angina (RR for lowest quintile ؍ 4.1; P for trend ؍ 0.
… and Vascular Biology, 1992
The incidence of coronary heart disease (CHD) in middle-aged men is more than three times higher in Northern Ireland than in France. The ECTIM study, which is based on WHO MONICA centers in Belfast (Northern Ireland), Strasbourg (eastern France), Toulouse (southwestern France), and Lille (northern France), has been established to investigate this striking difference. Male patients aged 25-64 years with myocardial infarction (MI) and control subjects sampled from the general population were recruited in the four centers. Hypolipidemic drug treatment was much more frequent in France than in Belfast. "Hypercholesterolemia" denned by the presence of hypolipidemic drug treatment or a low density liproprotein cholesterol level >200 mg/dl was more frequent in cases than in controls in both countries but was similar in both control groups. An in-depth study of lipid variables, including measurements of cholesterol fractions, triglycerides, apolipoproteins (apo), and lipoprotein particles (Lp), was performed in nonhypercholesterolemic subjects. In Northern Ireland and France, patients in comparison with controls had lower levels of high density lipoprotein cholesterol, apo A-I, apo A-II, Lp A-I, and Lp A-II: A-I and higher levels of Lp E:B and Lp(a):B. The levels of triglycerides, very low density lipoprotein cholesterol, apo B, and Lp C-III:B were higher in cases than in controls only in Belfast. In control subjects, the mean levels of cholesterol fractions and apolipoproteins were similar in Northern Ireland and France; however, the level of Lp A-I was lower and the levels of Lp E: B and Lp(a): B were higher in Northern Ireland than in France. A high-risk profile, characterized by a low Lp A-I level and by high levels of Lp E: B and Lp(a): B, was thus more frequent in the population of Northern Ireland. Further studies are needed to determine the contribution of environmental and genetic factors to this risk profile and to investigate its predictive value within populations. (Arteriosclerosis and Thrombosis 1992;12:701-707) KEY WORDS • lipoproteins • apolipoproteins • lipoprotein particles • case-control studies • geographical differences in coronary heart disease risk T o investigate the large international differences in the trends in coronary heart disease (CHD) incidence and mortality 1 and to study their relation to risk factor levels over time, the World Health Organization established the MONICA Project (Multinational MONItoring of trends and determinants in CArdiovascular disease). 2 The project's framework is
Apolipoprotein(a) isoforms and coronary heart disease in men
Atherosclerosis, 1997
The objective of the present study was to examine the possible associations between low molecular weight (LMW) apolipoprotein(a) (apo(a)) isoforms (F,B,S1,S2) and coronary heart disease (CHD). We conducted a nested case-control (prospective) study of five cohorts of white men: The 1936 cohort (baseline 1976, n= 548) and four cohorts from MONICA I born in 1923 (n=463), 1933 (n= 491), 1943 (n =504) and 1953 (n=448) studied at baseline in 1983. At follow up in 1991, 52 subjects had developed a first myocardial infarction and 22 had been hospitalized with angina pectoris. Plasma samples obtained at baseline were stored frozen until 1993-94, when case samples (n= 74) were analyzed together with samples from matched (disease free) controls (n=190). In a statistical model (conditional logistic regression) including all age groups, cholesterol (or apo B) level (PB0.01), systolic blood pressure (P=0.05) and smoking (P =0.02) predicted CHD. In the statistical model Lp(a) interacted significantly with age (OR= 5.7; 95% CI: 1.4-23.6; P= 0.016), and high Lp(a) (over 45 mg/dl) was associated with significantly increased risk in subjects under 60 years (OR= 3.82; 95% CI: 1.47 -9.96), but not in older men (OR= 0.67; 95% CI: 0.235-1.89). Therefore, we studied the impact of Lp(a)/apo(a) and other variables in subjects who had been under 60 years when they became cases. Among the younger subjects the presence of LMW apo(a) isoforms significantly predicted the development of CHD (OR=3.83; 95% CI: 1.18-12.4). The increased risk pertained to high Lp(a) (above versus below 45 mg/dl: OR = 3.68; 95% CI: 1.03-13.10), and to Lp(a) concentrations when entered into the model as a continuous variable (P =0.04). Cholesterol or apo B (PB 0.01), smoking (P=0.02), systolic blood pressure (P = 0.05) and low alcohol consumption (under nine drinks/week) (P=0.04) were also significant predictors of CHD. We conclude that LMW apo(a) isoforms are significantly associated with increased risk of CHD in men under 60 years.
Atherosclerosis, 2000
Apolipoprotein (apo) AI is distributed within high-density lipoproteins (HDL) between different types of particles, one containing both apoAI and apoAII (LpAI:AII), the other containing no apoAII (LpAI). We investigated the associations between LpAI and LpAI:AII with several factors such as body mass index (BMI), waist to hip ratio (WHR), alcohol intake, cigarette consumption and physical activity, in three French and one Northern Irish male populations included in a prospective study (PRIME study). LpAI and LpAI:AII were associated with variations in all environmental factors, except LpAI:AII, which was not associated with WHR. These relationships were unchanged after adjustment for other environmental factors, but slightly modified after adjustment for triglyceride levels. LpAI decreased when BMI, WHR and cigarette smoking increased, and increased with alcohol consumption and physical activity. LpAI:AII had a similar variation except for the absence of LpAI:AII modification associated with WHR variation. The associations between LpAI and BMI, alcohol consumption and cigarette smoking were largely dependent on HDL-cholesterol as indicated by the lack of any significance when the adjustment for HDL-cholesterol was made. Conversely, after adjustment for HDL-cholesterol, the significant association between LpAI:AII and BMI disappeared, while the associations between LpAI:AII and alcohol consumption, cigarette smoking and physical activity remained significant. These results suggest that the mechanisms of LpAI and LpAI:AII modulations differ according to each environmental factor, some dependent on the lipid content of lipoproteins and others not, but LpAI and LpAI:AII levels seem independent of triglyceride concentration.
Lipoprotein(a) and its position among other risk factors of atherosclerosis
Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28+/-35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in ...
Journal of Internal Medicine, 2002
Lundstam ULF, Herlitz J, Karlsson T, Linde Ân T, Wiklund O (Sahlgrenska University Hospital, Go Èteborg University, Go Èteborg; Sweden) Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease. J Intern Med 2002; 251: 111±118.
Atherosclerosis, 2000
The clinical utility of a new assay for plasma lipoprotein(a)-cholesterol (Lp(a)-C) was assessed in parallel with our routine Lp(a) mass measurements in a nested-case control study of subjects within the placebo arm of the West of Scotland Coronary Prevention Study (WOSCOPS). A total of 238 control patients and 108 patients who had suffered a serious vascular event during the course of the WOSCOPS were examined. Lp(a) mass was assessed within 2 years of sampling by an ELISA method on baseline EDTA plasma samples which had been stored at − 70°C. Subsequently, the Lp(a) mass was re-measured by an immunoturbidimetric assay 8 years after sampling. On the same stored aliquot the Lp(a)-C was measured. These analyses allowed us to assess whether the Lp(a)-C assay could provide any additional information over and above that which would be obtained from our Lp(a) mass assays. In addition the apo(a) isoform sizes of these subjects were measured using a high resolution immunoblotting system. The Lp(a)-C and Lp(a) mass measurements provided exactly the same information in the study, as they were equally non-discriminatory between cases and controls. The only difference between the two patient groups was the percentage of 'null' apo(a) alleles (control: 25.6% versus cases: 19.4%). We conclude that these results reinforce the concordance of the two assay systems and confirm that the Lp(a)-C assay provides no added information over and above that gained from traditional Lp(a) mass assays, which may be faster and less expensive.