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Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis.
JAMA 2007; 297(5):499-508JAMA

Abstract

CONTEXT

Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary atherosclerosis. However, no data exist describing the relationship between statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and disease progression.

OBJECTIVE

To investigate the relationship between changes in LDL-C and HDL-C levels and atheroma burden.

DESIGN, SETTING, AND PATIENTS

Post-hoc analysis combining raw data from 4 prospective randomized trials (performed in the United States, North America, Europe, and Australia between 1999 and 2005), in which 1455 patients with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or for 24 months. Ultrasound analysis was performed in the same core laboratory for all of the studies.

MAIN OUTCOME MEASURE

Relationship between changes in lipoprotein levels and coronary artery atheroma volume.

RESULTS

During statin therapy, mean (SD) LDL-C levels were reduced from 124.0 (38.3) mg/dL (3.2 [0.99] mmol/L) to 87.5 (28.8) mg/dL (2.3 [0.75] mmol/L) (a 23.5% decrease; P<.001), and HDL-C levels increased from 42.5 (11.0) mg/dL (1.1 [0.28] mmol/L) to 45.1 (11.4) mg/dL (1.2 [0.29] mmol/L) (a 7.5% increase; P<.001). The ratio of LDL-C to HDL-C was reduced from a mean (SD) of 3.0 (1.1) to 2.1 (0.9) (a 26.7% decrease; P<.001). These changes were accompanied by a mean (SD) increase in percent atheroma volume from 39.7% (9.8%) to 40.1% (9.7%) (a 0.5% [3.9%] increase; P = .001) and a mean (SD) decrease in total atheroma volume of 2.4 (23.6) mm3 (P<.001). In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-HDL cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely correlated with atheroma progression. In multivariate analysis, mean levels of LDL-C (beta coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (beta coefficient, -0.26 [95% confidence interval, -0.41 to -0.10]) remained independent predictors of atheroma regression. Substantial atheroma regression (> or =5% reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; P<.001). No significant differences were found with regard to clinical events.

CONCLUSIONS

Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by more than 7.5%. These findings suggest that statin benefits are derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C, although it remains to be determined whether the atherosclerotic regression associated with these changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical outcomes.

Authors+Show Affiliations

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. nichols1@ccf.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17284700

Citation

Nicholls, Stephen J., et al. "Statins, High-density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis." JAMA, vol. 297, no. 5, 2007, pp. 499-508.
Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297(5):499-508.
Nicholls, S. J., Tuzcu, E. M., Sipahi, I., Grasso, A. W., Schoenhagen, P., Hu, T., ... Nissen, S. E. (2007). Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA, 297(5), pp. 499-508.
Nicholls SJ, et al. Statins, High-density Lipoprotein Cholesterol, and Regression of Coronary Atherosclerosis. JAMA. 2007 Feb 7;297(5):499-508. PubMed PMID: 17284700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. AU - Nicholls,Stephen J, AU - Tuzcu,E Murat, AU - Sipahi,Ilke, AU - Grasso,Adam W, AU - Schoenhagen,Paul, AU - Hu,Tingfei, AU - Wolski,Kathy, AU - Crowe,Tim, AU - Desai,Milind Y, AU - Hazen,Stanley L, AU - Kapadia,Samir R, AU - Nissen,Steven E, PY - 2007/2/8/pubmed PY - 2007/2/10/medline PY - 2007/2/8/entrez SP - 499 EP - 508 JF - JAMA JO - JAMA VL - 297 IS - 5 N2 - CONTEXT: Statins reduce low-density lipoprotein cholesterol (LDL-C) levels and slow progression of coronary atherosclerosis. However, no data exist describing the relationship between statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and disease progression. OBJECTIVE: To investigate the relationship between changes in LDL-C and HDL-C levels and atheroma burden. DESIGN, SETTING, AND PATIENTS: Post-hoc analysis combining raw data from 4 prospective randomized trials (performed in the United States, North America, Europe, and Australia between 1999 and 2005), in which 1455 patients with angiographic coronary disease underwent serial intravascular ultrasonography while receiving statin treatment for 18 months or for 24 months. Ultrasound analysis was performed in the same core laboratory for all of the studies. MAIN OUTCOME MEASURE: Relationship between changes in lipoprotein levels and coronary artery atheroma volume. RESULTS: During statin therapy, mean (SD) LDL-C levels were reduced from 124.0 (38.3) mg/dL (3.2 [0.99] mmol/L) to 87.5 (28.8) mg/dL (2.3 [0.75] mmol/L) (a 23.5% decrease; P<.001), and HDL-C levels increased from 42.5 (11.0) mg/dL (1.1 [0.28] mmol/L) to 45.1 (11.4) mg/dL (1.2 [0.29] mmol/L) (a 7.5% increase; P<.001). The ratio of LDL-C to HDL-C was reduced from a mean (SD) of 3.0 (1.1) to 2.1 (0.9) (a 26.7% decrease; P<.001). These changes were accompanied by a mean (SD) increase in percent atheroma volume from 39.7% (9.8%) to 40.1% (9.7%) (a 0.5% [3.9%] increase; P = .001) and a mean (SD) decrease in total atheroma volume of 2.4 (23.6) mm3 (P<.001). In univariate analysis, mean levels and treatment-mediated changes in LDL-C, total cholesterol, non-HDL cholesterol, apolipoprotein B, and ratio of apolipoprotein B to apolipoprotein A-I were significantly correlated with the rate of atherosclerotic progression, whereas treatment-mediated changes in HDL-C were inversely correlated with atheroma progression. In multivariate analysis, mean levels of LDL-C (beta coefficient, 0.11 [95% confidence interval, 0.07-0.15]) and increases in HDL-C (beta coefficient, -0.26 [95% confidence interval, -0.41 to -0.10]) remained independent predictors of atheroma regression. Substantial atheroma regression (> or =5% reduction in atheroma volume) was observed in patients with levels of LDL-C less than the mean (87.5 mg/dL) during treatment and percentage increases of HDL-C greater than the mean (7.5%; P<.001). No significant differences were found with regard to clinical events. CONCLUSIONS: Statin therapy is associated with regression of coronary atherosclerosis when LDL-C is substantially reduced and HDL-C is increased by more than 7.5%. These findings suggest that statin benefits are derived from both reductions in atherogenic lipoprotein levels and increases in HDL-C, although it remains to be determined whether the atherosclerotic regression associated with these changes in lipid levels will translate to meaningful reductions in clinical events and improved clinical outcomes. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/17284700/Statins_high_density_lipoprotein_cholesterol_and_regression_of_coronary_atherosclerosis_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.297.5.499 DB - PRIME DP - Unbound Medicine ER -