Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

Autor: Sofat, Reecha, Cooper, Jackie A., Kumari, Meena, Casas, Juan P., Mitchell, Jacqueline P., Acharya, Jayshree, Thom, Simon, Hughes, Alun D., Humphries, Steve E., Hingorani, Aroon D.
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: PLoS Medicine
PLoS Medicine, Vol 13, Iss 10, p e1002146 (2016)
ISSN: 1549-1676
1549-1277
Popis: Background The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. Methods and Findings To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and −0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient −0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect. Conclusions In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.
Using longitudinal data, Reecha Sofat and colleagues probe the association between blood levels of ApoE and risk of cardiovascular disease.
Author Summary Why Was This Study Done? Heart attacks and strokes, jointly referred to as cardiovascular disease (CVD), are the most common causes of death worldwide. Identifying risk factors that can be used to predict these events can be valuable for prevention, and identifying molecular pathways involved in risk can be useful for the development of preventive drugs. ApoE is a circulating protein that binds to and may regulate circulating lipoproteins, which are proteins that combine with and transport lipids and fat in the bloodstream. ApoE has several genetic variants in the human population; in previous studies, certain ApoE variants (genotypes) have been shown to be associated with greater risk of CVD. One hypothesis is that the amount of ApoE protein circulating in the body, which has been shown to vary by ApoE genotype, mediates the risk of CVD. What Did the Researchers Do and Find? We measured ApoE concentrations directly in ~10,000 individuals, ~1,400 of whom had CVD events. We did not find any association of circulating ApoE with CVD, even after adjusting for other CVD-related factors that might obscure an association. We also placed ApoE concentration in the context of clinical risk equations that are used to assess risk in patients, and found that it did not improve risk prediction. What Do These Findings Mean? This study demonstrates that ApoE genotypes that confer risk of CVD might do so via protein function rather than protein concentration in the blood. ApoE may still be a drug target for prevention of CVD.
Databáze: OpenAIRE
Externí odkaz: