RESUMEN
AIMS: The atherogenic potential of cholesterol in triglyceride-rich lipoproteins, also called remnant cholesterol, is being increasingly acknowledged. Elevated remnant cholesterol is associated with increased risk of myocardial infarction and ischaemic stroke. We tested the hypothesis that elevated remnant cholesterol is also associated with increased risk of peripheral artery disease (PAD). METHODS AND RESULTS: We studied 106 937 individuals from the Copenhagen General Population Study recruited in 2003-15. During up to 15 years of follow-up, 1586 were diagnosed with PAD, 2570 with myocardial infarction, and 2762 with ischaemic stroke. We also studied 13 974 individuals from the Copenhagen City Heart Study recruited in 1976-78. During up to 43 years of follow-up, 1033 were diagnosed with PAD, 2236 with myocardial infarction, and 1976 with ischaemic stroke. Remnant cholesterol was calculated from a standard lipid profile. Diagnoses were from Danish nationwide health registries. In the Copenhagen General Population Study, elevated remnant cholesterol levels were associated with higher risk of PAD, up to a multivariable adjusted hazard ratio (HR) of 4.8 (95% confidence interval 3.1-7.5) for individuals with levels ≥1.5 mmol/L (58 mg/dL) vs. <0.5 mmol/L (19 mg/dL). Corresponding results were 4.2 (2.9-6.1) for myocardial infarction and 1.8 (1.4-2.5) for ischaemic stroke. In the Copenhagen City Heart Study, corresponding HRs were 4.9 (2.9-8.5) for PAD, 2.6 (1.8-3.8) for myocardial infarction, and 2.1 (1.5-3.1) for ischaemic stroke. CONCLUSION: Elevated remnant cholesterol is associated with a five-fold increased risk of PAD in the general population, higher than for myocardial infarction and ischaemic stroke.
Asunto(s)
Isquemia Encefálica , Hipercolesterolemia , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Enfermedad Arterial Periférica , Accidente Cerebrovascular , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , Colesterol , Humanos , Hipercolesterolemia/complicaciones , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/etiología , TriglicéridosRESUMEN
Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly (P<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 [95% CI, 0.41-0.85]), whereas early vascular aging had higher risk (hazard ratio, 2.70 [95% CI, 1.55-4.70]) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.