Mika Hilvo1, Indu Dhar2, Mitja Lääperi1, Vegard Lysne2,3, Gehard Sulo4, Grethe S Tell5,6, Pekka Jousilahti7, Ottar K Nygård3, Hermann Brenner8, Ben Schöttker8,9, Reijo Laaksonen1,10. 1. Zora Biosciences Oy, Tietotie 2C, 02150 Espoo, Finland. 2. Department of Clinical Science, Centre for Nutrition, University of Bergen, Klinisk institutt 1, Postboks 7804, 5020 Bergen, Norway. 3. Department of Heart Disease, Haukeland University Hospital, Jonas Lies vei 65, 5021 Bergen, Norway. 4. Centre for Disease Burden, Division of Mental and Physical Health, Norwegian Institute of Public Health, Zander Kaaesgate 7, 5015 Bergen, Norway. 5. Department of Global Public Health and Primary Care, University of Bergen, Årstadveien 17, 5020 Bergen, Norway. 6. Division of Mental and Physical Health, Norwegian Institute of Public Health, Zander Kaaes gate 7, 5808 Bergen, Norway. 7. Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Mannerheimintie 166, 00271 Helsinki, Finland. 8. Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. 9. Network Aging Research, University of Heidelberg, Bergheimer Strasse 20, 69115 Heidelberg, Germany. 10. Finnish Cardiovascular Research Center, University of Tampere, Tampere University Hospital, Arvo Ylpön Katu 34, 33520 Tampere, Finland.
Abstract
AIMS: Low-density lipoprotein cholesterol (LDL-C) is an established causal driver of atherosclerotic cardiovascular disease (ASCVD), but its performance and age-dependency as a biomarker for incident events and mortality arising from ASCVD is less clear. The aim was to determine the value of LDL-C as a susceptibility/risk biomarker for incident coronary heart disease (CHD), ASCVD, and stroke events and deaths, for the age groups <50 and ≥50 years. METHODS AND RESULTS: The performance of LDL-C was evaluated in three cohorts, FINRISK 2002 (n = 7709), HUSK (n = 5431), and ESTHER (n = 4559), by Cox proportional hazards models, C-statistics, and net reclassification index calculations. Additionally, the hazard ratios (HRs) for the three cohorts were pooled by meta-analysis. The most consistent association was observed for CHD [95% confidence interval (CI) for HRs per standard deviation ranging from 0.99 to 1.37], whereas the results were more modest for ASCVD (0.96-1.18) due to lack of association with stroke (0.77-1.24). The association and discriminatory value of LDL-C with all endpoints in FINRISK 2002 and HUSK were attenuated in subjects 50 years and older [HRs (95% CI) obtained from meta-analysis 1.11 (1.04-1.18) for CHD, 1.15 (1.02-1.29) for CHD death, 1.02 (0.98-1.06) for ASCVD, 1.12 (1.02-1.23) for ASCVD death, and 0.97 (0.89-1.05) for stroke]. CONCLUSION: In middle-aged and older adults, associations between LDL-C and all the studied cardiovascular endpoints were relatively weak, while LDL-C showed stronger association with rare events of pre-mature CHD or ASCVD death among middle-aged adults. The predictive performance of LDL-C also depends on the studied cardiovascular endpoint. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Low-density lipoprotein cholesterol (LDL-C) is an established causal driver of atherosclerotic cardiovascular disease (ASCVD), but its performance and age-dependency as a biomarker for incident events and mortality arising from ASCVD is less clear. The aim was to determine the value of LDL-C as a susceptibility/risk biomarker for incident coronary heart disease (CHD), ASCVD, and stroke events and deaths, for the age groups <50 and ≥50 years. METHODS AND RESULTS: The performance of LDL-C was evaluated in three cohorts, FINRISK 2002 (n = 7709), HUSK (n = 5431), and ESTHER (n = 4559), by Cox proportional hazards models, C-statistics, and net reclassification index calculations. Additionally, the hazard ratios (HRs) for the three cohorts were pooled by meta-analysis. The most consistent association was observed for CHD [95% confidence interval (CI) for HRs per standard deviation ranging from 0.99 to 1.37], whereas the results were more modest for ASCVD (0.96-1.18) due to lack of association with stroke (0.77-1.24). The association and discriminatory value of LDL-C with all endpoints in FINRISK 2002 and HUSK were attenuated in subjects 50 years and older [HRs (95% CI) obtained from meta-analysis 1.11 (1.04-1.18) for CHD, 1.15 (1.02-1.29) for CHD death, 1.02 (0.98-1.06) for ASCVD, 1.12 (1.02-1.23) for ASCVD death, and 0.97 (0.89-1.05) for stroke]. CONCLUSION: In middle-aged and older adults, associations between LDL-C and all the studied cardiovascular endpoints were relatively weak, while LDL-C showed stronger association with rare events of pre-mature CHD or ASCVD death among middle-aged adults. The predictive performance of LDL-C also depends on the studied cardiovascular endpoint. Published on behalf of the European Society of Cardiology. All rights reserved.