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Apoliprotein E genotypes very long-term outcomes: an unexpected finding regarding diabetes incidence.
Session:
Posters 3 - Écran 01 - Cardiologia Clínica/Miscelânia
Speaker:
Cátia Santos Ferreira
Congress:
CPC 2018
Topic:
J. Preventive Cardiology
Theme:
28. Risk Factors and Prevention
Subtheme:
28.7 Diabetes and the Heart
Session Type:
Posters
FP Number:
---
Authors:
Cátia Santos Ferreira; Manuel Oliveira Santos; Regina Costa; James Milner; Rui Baptista; Patrícia Dias; José Pereira de Moura; Mariano Pêgo
Abstract
<p><strong>BACKGROUND: </strong>Apolipoprotein E (ApoE) locus has three common alleles; the E4 allele is associated with increased cardiovascular (CV) risk, compared with wild-type E3/E3. Additionally, controversy exists whether these polymorphisms have impact on cancer and diabetes mellitus (DM) incidence.</p> <p><strong>POPULATION AND METHODS: </strong>We prospectively included 463 patients treated at the Lipidology Clinic from 1994 to 2007. All patients were genotyped regarding the ApoE locus and were followed for a median (interquartile range) time of 15.1 (12.3-17.4) years (all >10 years). Patients with previous CV events (n=19) and with E4/E2 genotype (n=8) were excluded due to conflicting effects on outcomes. The primary endpoint was a composite of CV mortality, myocardial infarction and stroke. The secondary endpoints included all-cause mortality, DM and cancer.</p> <p><strong>RESULTS: </strong>The most prevalent allele was ApoE3 (283 homozygotes), followed by ApoE4 (102 carriers) and ApoE2 (51 carriers). Demographic data was similar between the groups except for age (ApoE4: mean 44.1±14.8 years, younger than ApoE2 and ApoE3, 50.5±13.9, p<0.05) and blood pressure (ApoE4: mean 128/81 mmHg, inferior to ApoE3 and ApoE2, 136/84 mmHg, p<0.05). The 10-year CV mortality rate was 1.4% (intermediate-low risk considering the SCORE CV risk stratification system). At the 10-year follow-up, no differences were found regarding the primary endpoint incidence for ApoE4 (HR 1.08; 95%CI 0.45-2.58, p=0.87) or ApoE2 carriers (HR 0.95; 95%CI 0.28-3.24, p=0.93) versus the wild-type ApoE3. All cause-mortality at follow-up was 9.9%, with no differences found between the three ApoE groups (p=0.52). Conversely, DM incidence at follow-up in ApoE3 and ApoE4 carriers (33.5% and 34.4%, respectively) was significantly lower compared to ApoE2 carriers (52.4%, p=0.017). The age-adjusted odds ratio for DM in ApoE2 patients was 1.95 (1.00-3.78, p=0.049), versus non-ApoE2 carriers. The cancer incidence at follow-up in wild-type ApoE3 was 9.6%; in ApoE4 carriers was 6.8%. Although not reaching statistical significance (p=0.37), ApoE2 carriers had a numerical higher incidence (14.7%) of cancer.</p> <p><strong>CONCLUSION: </strong>In a large, prospective, cohort of patients under lipid-lowering therapy with a very long-term follow-up, no interaction was found between ApoE genotypes and CV outcomes, cancer risk or mortality. Interestingly, we found a 2-fold DM incidence in ApoE2 carriers. This may prompt strategies for earlier diagnosis and treatment in this selected group.</p>
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