Further, that APOE4 predisposes the CV to damage by, and exacerbates the effects of, additional risk factors (such as sex, hypertension, and diabetes).
Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status.
Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension and <i>Apolipoprotein E-</i>ε4 status and the impact of duration and control of hypertension.
Predictors of MCI were APOE ε4 allele (hazard ratio [HR] 1.89; p = 0.008), current depressive symptoms (HR 1.78; p = 0.02), midlife onset of hypertension (HR 2.43; p = 0.005), increasing number of vascular diseases (HR 1.13; p = 0.02), and chronic conditions from the Charlson Comorbidity Index (HR 1.08; p = 0.006).
While midlife HTN is not associated with late life cognitive impairment, midlife SBP is related to late life attention and verbal fluency impairments, particularly among ApoE4+ individuals.
The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition.
In hypertension, the association between APOE-ε4 and executive function was also only significant in participants with lower CO2 vasoreactivity (P = .005 for APOE by CO2 vasoreactivity).
Hypertension moderated the effects of APOE ε4 on the rate of change for cognitive flexibility, such that the presence of the APOE ε4 allele and hypertension was associated with steeper cognitive decline over a 21-year period.
APOE genotype significantly modified the associations between both midlife hypertension and cardiovascular disease and decline in language abilities and midlife diabetes and decline in verbal memory, attention, and visuospatial abilities.
Carriers of the ESR1 p allele had significantly greater declines in logical memory compared to participants with the PP genotype, independent of demographic characteristics (e.g. age), chronic illness (e.g. hypertension), sleep aid usage, hormone levels, apolipoprotein E e4 status and prospective changes in mood, smoking and alcohol consumption.
An overall comparison of the ApoE gene alleles ɛ4 with ɛ3 yielded a significant 81% increased risk for hypertension (95% confidence interval (95% CI): 1.41-2.32; P<0.0005).
In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons.
TGF-beta(1) may cause endothelial dysfunction in apolipoprotein E-deficient (apoE(-/-)) mice via stimulation of reactive oxygen species (ROS) production by the NADPH oxidase (NOX) system and aggravate aortic and heart remodeling and hypertension.
Our results not only demonstrated potential interactions of APOE epsilon2/epsilon3/epsilon4 and LDLR C1773T polymorphisms with risk of having ischemic stroke, but also added the evidence of independent role of hypertension and APOE epsilon2/epsilon3/epsilon4 polymorphism in the development of this disorder in Northern Han Chinese.
Furthermore, after restricting our analysis to Asian populations, the contrasts between the risk of hypertension among individuals possessing ApoE epsilon4 vs. epsilon3 and ApoE4/4 vs. ApoE3/3 were positively reinforced, with ORs of 1.97 (95% CI, 0.93 to 4.15; P=0.08) and 2.27 (95% CI, 1.03 to 4.98; P=0.04), respectively.
In multivariate, random-effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE epsilon4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not.
We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E epsilon4) and a vascular risk factor (hypertension) in a sample of 189 volunteers (age 18-82).