Setor K Kunutsor1, Hassan Khan2, Kristiina Nyyssönen3, Jari A Laukkanen4. 1. School of Clinical Sciences, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Southmead Road, Bristol, UK. Electronic address: skk31@cantab.net. 2. Emory University School of Medicine, Atlanta, GA, USA. 3. Eastern Finland Laboratory Center, and Department of Clinical Chemistry, University of Eastern Finland, Kuopio, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 4. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Central Finland Central Hospital, Jyväskylä, Finland.
Abstract
BACKGROUND: Lipoprotein(a) [Lp(a)] is an established and independent risk factor for cardiovascular outcomes. However, the relationship of Lp(a) with risk of sudden cardiac death (SCD) is unknown. We aimed to assess the association of Lp(a) with risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1881 men aged 42-61years at recruitment. METHODS AND RESULTS: Plasma Lp(a) concentration was assessed at baseline and repeat measurements made several years apart. After a median follow-up of 24.7years, 141 SCDs were recorded. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and were corrected for within-person variability in Lp(a) levels. The regression dilution ratio of loge Lp(a) adjusted for age was 0.84 (95% CI: 0.81-0.88). Lipoprotein(a) levels were log-linearly associated with risk of SCD. In analyses adjusted for established risk factors, the HR (95% CI) for SCD per 1 standard deviation (3.56-fold) higher baseline loge Lp(a) was 1.24 (1.05-1.47; P=0.013). This remained consistent on further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein 1.23 (1.04-1.46; P=0.018). HRs remained unchanged after accounting for incident coronary events and did not vary importantly in several relevant clinical subgroups. Adding Lp(a) to a SCD risk prediction model did not significantly improve risk discrimination beyond established risk factors, but improved the continuous net reclassification 30.2% (1.1 to 59.2%, P=0.042). CONCLUSIONS: Available evidence shows a continuous and independent association between Lp(a) levels and risk of SCD. Further research is needed to replicate these findings.
BACKGROUND:Lipoprotein(a) [Lp(a)] is an established and independent risk factor for cardiovascular outcomes. However, the relationship of Lp(a) with risk of sudden cardiac death (SCD) is unknown. We aimed to assess the association of Lp(a) with risk of SCD in the Kuopio Ischemic Heart Disease prospective cohort study of 1881 men aged 42-61years at recruitment. METHODS AND RESULTS: Plasma Lp(a) concentration was assessed at baseline and repeat measurements made several years apart. After a median follow-up of 24.7years, 141 SCDs were recorded. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and were corrected for within-person variability in Lp(a) levels. The regression dilution ratio of loge Lp(a) adjusted for age was 0.84 (95% CI: 0.81-0.88). Lipoprotein(a) levels were log-linearly associated with risk of SCD. In analyses adjusted for established risk factors, the HR (95% CI) for SCD per 1 standard deviation (3.56-fold) higher baseline loge Lp(a) was 1.24 (1.05-1.47; P=0.013). This remained consistent on further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein 1.23 (1.04-1.46; P=0.018). HRs remained unchanged after accounting for incident coronary events and did not vary importantly in several relevant clinical subgroups. Adding Lp(a) to a SCD risk prediction model did not significantly improve risk discrimination beyond established risk factors, but improved the continuous net reclassification 30.2% (1.1 to 59.2%, P=0.042). CONCLUSIONS: Available evidence shows a continuous and independent association between Lp(a) levels and risk of SCD. Further research is needed to replicate these findings.
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