Combined Effects of Small Apolipoprotein (a) Isoforms and Small, Dense LDL on Coronary Artery Disease Risk (original) (raw)
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Clinical Chemistry and Laboratory Medicine (CCLM), 2006
Background: The ratio of low-to high-density lipoprotein-cholesterol (LDL-C/HDL-C) conventionally represents the balance of proatherogenic and antiatherogenic lipids. However, growing evidence supports the idea that the ratio of apolipoprotein (apo) B/ apoAI is a better index for risk assessment of coronary artery disease (CAD). The aim of this study was to evaluate the efficiency of advanced profile of serum (apo)lipoproteins for predicting stable CAD in secondary prevention. Methods: The study subjects, 138 men and 126 women aged 40-70 years, were classified as CAD cases or controls, according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and extent of lesions in coronary arteries. Serum (apo)lipoproteins were measured by immunoturbidometric and electrophoresis methods. Results: Patients with CAD compared with controls had increased serum levels of triglycerides (2.6"2.0 vs. 2.0"1.2 mmol/L, pF0.005), apoB (1.36"0.31 vs. 1.19"0.24 g/L, pF0.0001), lipoprotein(a) wLp(a)x (0.69"0.60 vs. 0.43"0.31 g/L, pF0.0001) and apoB/ apoAI ratio (1.07"0.32 vs. 0.87"0.18, pF0.0001), and decreased serum levels of HDL-C (1.02"0.29 vs. 1.11"0.34 mmol/L, pF0.03), apoAI (1.32"0.22 vs. 1.37"0.19 g/L, pF0.04) and LDL-C/apoB ratio (0.91"0.32 vs. 1.02"0.25 mmol/g, pF0.01). Multiple logistic regression analysis after adjusting for major risk factors showed that the apoB/apoAI ratio, apoB and Lp(a) were among seven significant and independent determinants of CAD. The area under the receiver operating characteristic (ROC) curves (AUC) as a relative measure of test efficiency was highest and significant for the apoB/apoAI ratio (AUCs0.71, pF0.0001), apoB (0.67, pF0.0001), Lp(a) (0.63, pF0.001), the LDL-C/apoB ratio (0.62, pF0.006), triglycerides (0.62, pF0.004) and apoAI (0.58, pF0.05). ANOVA analysis showed significant association for the apoB/apoAI ratio, apoB, Lp(a) and triglycerides, and moderate association for total cholesterol and its subfractions, with the severity of CAD. Conclusions: The results indicate that the apoB/apoAI ratio, apoB and Lp(a) are independent risk factors for
The Journal of Lipid Research, 2011
Lipoprotein(a) (Lp(a)) was fi rst described by Berg in 1963 (1). Lp(a) is a lipoprotein similar in structure to LDL, but differs from LDL in having apo(a), a large glycoprotein, attached to apoB-100 by a disulfi de bond (2). Apo(a) shares strong homology with several regions of plasminogen (3), including the protease domain, the kringle 5 domain, and 10 types of the kringle 4 domain. It has been shown that apo(a) is highly polymorphic in size due to different numbers of the kringle 4 type 2 (kringle-4 2) domain, ranging from a minimum of 3 to greater than 40 (4). Plasma levels of Lp(a) are highly heritable (2, 5) and are inversely correlated with the apo(a) isoform size, with subjects carrying small isoforms having high plasma Lp(a) levels (5). Metabolic studies have shown that the inverse association between plasma Lp(a) levels and apo(a) isoform size is due to differences in the hepatic secretion of apo(a), with subjects carrying small apo(a) isoforms having increased apo(a) secretion (6, 7). Boerwinkle et al. (8) indicated that 69% of the variability in plasma Lp(a) levels is accounted for by the number of apo(a) kringle-4 2 repeats, and an additional 21% of the variation is explained by other sequences within the gene coding for apo(a). Recently, the rs3798220 single-nucleotide polymorphism (SNP) in the apo(a) locus was found to be a strong predictor of Lp(a) levels and coronary heart disease (CHD) risk (9). Plasma Lp(a) levels are associated with CHD risk (10, 11). The mechanisms by which Lp(a) increases CHD risk are not well defi ned, but may include both a prothrombotic effect due to the similarity of apo(a) to the fi brinolytic pro-enzyme plasminogen (12, 13), and an atherogenic effect mediated by the preferential binding of oxidized phospholipids by Lp(a) as well as Lp(a) deposition in the arterial wall (14).
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.
Journal of cardiology, 2008
Background: Worldwide coronary heart disease (CHD) is estimated to be the leading cause of death. Current knowledge about prevention of CHD is mainly derived from developed countries. Therefore, this study aimed to find out the association of CHD with ratios of different lipoproteins and apolipoproteins, LDL particle size, as well as different traditional risk factors in Asian Indian population in Eastern part of India. Methods: Case-control study of 100 patients with CHD and 98 healthy controls were age and sex matched. After clinical evaluation, blood samples were collected for biochemical assays. Results: Multivariate logistic regression analysis found apoB (OR 2.96; 95% CI 1.02-8.54), apoB/HDL-c (OR 4.14; 95% CI 1.33-12.83), nonHDL-c (OR 5.41; 95% CI 2.08-14.10), apoB/apoAI (OR 6.64; 95% CI 2.37-18.57), and LDL particle size (9.59; 95% CI 2.92-31.54) were independently associated with CHD. Area under the ROC curves derived from the model (AUROC 0.947; 95% CI 0.916-0.977) are significantly higher than any other variables. Conclusions: Findings from the multivariate analysis, apoB, apoB/HDL-c, nonHDL-c, apoB/apoAI, and LDL particle size are potent indicators and useful for diagnosis of predisposed 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.
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.
Lipoprotein(a) and LDL Particle Size Are Related to the Severity of Coronary Artery Disease
Cardiology, 2007
level and mean LDL particle size were significantly correlated with a high Gensini score. LDL particle size in the CAD group was smaller than in the control group (26.74 8 0.64 vs. 26.43 8 0.93 nm, p ! 0.001). The Gensini score was significantly higher in small LDL with high Lp(a) level groups. Conclusion: The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD.
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.