- Email: [email protected]
1ML01 Non-HDL-C as a risk factor: Emerging evidence with atherogenic apoB-containing lipoproteins (VLDL, IDL, and LDL)
18
Monday September 29, 2003: Master’s Lecture 1ML01
Non-HDL-C as a risk factor: Emerging evidence with atherogenic apoB-containing lipoproteins (VLDL, IDL and LDL)
J. Chapman. Unit 551, INSERM, Hopital de la Pitié, Paris, France The most common forms of atherogenic dyslipidemia are characterised by disequilibrium between elevated circulating levels of proatherogenic apoBcontaining lipoproteins (VLDL, VLDL remnants, IDL and LDL) and a relative deficiency of anti-atherogenic high-density lipoproteins (HDL). When reverse cholesterol transport mediated by HDL is attenuated, then such disequilibrium favors cholesterol deposition in peripheral tissues and the arterial wall. Indeed, it is now established that all lipoprotein particles containing apoB100 traverse the arterial endothelium to penetrate the intima, where they bind to extracellular matrix components and undergo retention; leading to arterial cholesterol accumulation in both extra- and intracellular forms, a key feature of the lipid-rich, atherosclerotic plaque. The CV risk due to atherogenic lipoproteins at the arterial wall is optimally represented by a measure that reflects their total concentration, and it has been suggested that non-HDL-C could reflect such combined risk. Non-HDL-C corresponds to plasma total cholesterol minus HDL-C. Measurement of this biomarker of CV risk is especially appropriate in dyslipidemic subjects under statin therapy, as potent statins effect reduction not only in LDL and its subfractions (including small dense LDL) but also in VLDL, VLDL remnants and IDL; in this way, the full therapeutic impact of statin treatment may be evaluated. It is especially relevant that both the Strong Heart Study in Type II diabetes and the BARI study (Bypass Angioplasty Revascularisation Investigation) in patients with multivessel coronary artery disease showed non-HDL-C to represent a strong and independent predictor of both fatal and nonfatal CV disease; moreover, the utility of this biomarker was shown to extend over a wide range of TG concentration. Non-HDL-C therefore constitutes an appropriate treatment target among patients with coronary heart disease.
1ML02
Coronary risk factors in Japanese population - Implications of the J-LIT study
M. Matsuzaki. Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan The Japan Lipid Intervention Trial (J-LIT) is the first large-scale nationwide cohort study designed to clarify the relationship between lipid levels and incidence of CHD or mortality in ordinary clinical settings. Total of 52,421 patients with hypercholesterolemia (TC≥220 mg/dL), men and postmenopausal women (mean age: 57.9 years old, women: 66.8%) were treated with simvastatin 5 mg/day for 6 years. The primary endpoint was acute myocardial infarction or sudden cardiac death, and the secondary endpoint was total death. Significant reduction was occurred in TC and LDL-C levels, and sustained for 6 years. The coronary event rate was 0.91/1,000 patients-years in the primary prevention cohort without prior CHD whereas the rate was 5 times higher than in the secondary prevention cohort with documented CHD (4.45/1,000 pts-years). The risk of coronary events increased with TC and LDL-C levels, and was inversely correlated to HDL-C level; the relationship was similar in both cohorts. Male, age, hypertension, diabetes mellitus, ECG abnormality, cerebrovascular disease, family history of CHD, and smoking were also coronary risk factors. A minority of patients (1.4%) had unexpected significant reduction in TC level (>40%) with higher mortality; close monitoring of those patients is recommended. Coronary events were much lower in this study than in comparable epidemiological Framingham Heart Study or the PROCAM study of Western population. Nevertheless, the relations of coronary risk to lipid levels and other coronary risk factors were similar in both populations. In the HPS study, coronary events were effectively reduced with statin in patients with relatively normal serum cholesterol level and concomitant multiple risk factors. Multiplied risk of coronary events by concomitant risk factors was also found in J-LIT study, suggesting risk-factor modification has universal benefits, despite lower incidence of CHD in Japan.
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
Monday September 29, 2003: Master’s Lecture 1ML01
Non-HDL-C as a risk factor: Emerging evidence with atherogenic apoB-containing lipoproteins (VLDL, IDL and LDL)
J. Chapman. Unit 551, INSERM, Hopital de la Pitié, Paris, France The most common forms of atherogenic dyslipidemia are characterised by disequilibrium between elevated circulating levels of proatherogenic apoBcontaining lipoproteins (VLDL, VLDL remnants, IDL and LDL) and a relative deficiency of anti-atherogenic high-density lipoproteins (HDL). When reverse cholesterol transport mediated by HDL is attenuated, then such disequilibrium favors cholesterol deposition in peripheral tissues and the arterial wall. Indeed, it is now established that all lipoprotein particles containing apoB100 traverse the arterial endothelium to penetrate the intima, where they bind to extracellular matrix components and undergo retention; leading to arterial cholesterol accumulation in both extra- and intracellular forms, a key feature of the lipid-rich, atherosclerotic plaque. The CV risk due to atherogenic lipoproteins at the arterial wall is optimally represented by a measure that reflects their total concentration, and it has been suggested that non-HDL-C could reflect such combined risk. Non-HDL-C corresponds to plasma total cholesterol minus HDL-C. Measurement of this biomarker of CV risk is especially appropriate in dyslipidemic subjects under statin therapy, as potent statins effect reduction not only in LDL and its subfractions (including small dense LDL) but also in VLDL, VLDL remnants and IDL; in this way, the full therapeutic impact of statin treatment may be evaluated. It is especially relevant that both the Strong Heart Study in Type II diabetes and the BARI study (Bypass Angioplasty Revascularisation Investigation) in patients with multivessel coronary artery disease showed non-HDL-C to represent a strong and independent predictor of both fatal and nonfatal CV disease; moreover, the utility of this biomarker was shown to extend over a wide range of TG concentration. Non-HDL-C therefore constitutes an appropriate treatment target among patients with coronary heart disease.
1ML02
Coronary risk factors in Japanese population - Implications of the J-LIT study
M. Matsuzaki. Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan The Japan Lipid Intervention Trial (J-LIT) is the first large-scale nationwide cohort study designed to clarify the relationship between lipid levels and incidence of CHD or mortality in ordinary clinical settings. Total of 52,421 patients with hypercholesterolemia (TC≥220 mg/dL), men and postmenopausal women (mean age: 57.9 years old, women: 66.8%) were treated with simvastatin 5 mg/day for 6 years. The primary endpoint was acute myocardial infarction or sudden cardiac death, and the secondary endpoint was total death. Significant reduction was occurred in TC and LDL-C levels, and sustained for 6 years. The coronary event rate was 0.91/1,000 patients-years in the primary prevention cohort without prior CHD whereas the rate was 5 times higher than in the secondary prevention cohort with documented CHD (4.45/1,000 pts-years). The risk of coronary events increased with TC and LDL-C levels, and was inversely correlated to HDL-C level; the relationship was similar in both cohorts. Male, age, hypertension, diabetes mellitus, ECG abnormality, cerebrovascular disease, family history of CHD, and smoking were also coronary risk factors. A minority of patients (1.4%) had unexpected significant reduction in TC level (>40%) with higher mortality; close monitoring of those patients is recommended. Coronary events were much lower in this study than in comparable epidemiological Framingham Heart Study or the PROCAM study of Western population. Nevertheless, the relations of coronary risk to lipid levels and other coronary risk factors were similar in both populations. In the HPS study, coronary events were effectively reduced with statin in patients with relatively normal serum cholesterol level and concomitant multiple risk factors. Multiplied risk of coronary events by concomitant risk factors was also found in J-LIT study, suggesting risk-factor modification has universal benefits, despite lower incidence of CHD in Japan.
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan