Dysbetalipoproteinemia: differentiating multifactorial remnant cholesterol disease from genetic apoE deficiency

Background Dysbetalipoproteinemia (DBL) is characterized by the accumulation of remnant lipoprotein particles and associated with an increased risk of cardiovascular and peripheral vascular disease (PVD). DBL is thought to be mainly caused by the presence of an E2/E2 genotype of the apolipoprotein E (APOE) gene, in addition to environmental factors. However, there exists considerable variability in the phenotype of these patients. Objective The objectives were to verify the proportion of DBL subjects diagnosed using the gold standard Fredrickson criteria who did not carry E2/E2 and to compare the clinical characteristics of DBL patients with vs without E2/E2. Methods A total of 12 432 patients with lipoprotein ultracentrifugation as well as APOE genotype or apoE phenotype data were included in the present retrospective study. Results Among the 12 432 patients, 4% (n=524) were positive for Fredrickson criteria (F+), and only 38% (n=197) of the F+ individuals were E2/E2. The F+ E2/E2 group had significantly higher remnant cholesterol concentration (3.44 vs 1.89 mmol/L) and had higher frequency of DBL-related xanthomas (24% vs 2%) and floating beta (95% vs 11%) than the F+ non-E2/E2 group (p<0.0001). The F+ E2/E2 group had an independent higher risk of PVD (OR 11.12 (95% CI 1.87-66.05) p=0.008) events compared to the F+ non-E2/E2 group. Conclusion In the largest cohort of DBL worldwide, we demonstrated that the presence of E2/E2 was associated with a more severe DBL phenotype. We suggest that two dysbetalipoproteinemia phenotypes should be distinguished: the multifactorial remnant cholesterol disease and the genetic apoE deficiency disease.

Egg consumption, cholesterol intake, and risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study

ABSTRACTBackgroundEpidemiologic studies suggest inverse associations between consumption of egg, a major source of dietary cholesterol, and stroke. However, the evidence of the relation remains limited, especially among carriers of apolipoprotein E4 (apoE4), which influences cholesterol metabolism.ObjectiveThe aim of this study was to investigate associations of egg and cholesterol intakes with risk of stroke and with the major stroke risk factor, blood pressure, in middle-aged and older men from eastern Finland and whether apoE phenotype could modify these associations.MethodsA total of 1950 men aged 42–60 y in 1984–1989 were included at the baseline examinations of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Data on apoE phenotype were available for 1015 men. Dietary intakes were assessed with 4-d food records at baseline and incident stroke events were assessed by record linkage to hospital discharge registries. Cox proportional hazards regression analyses were used to estimate associations with stroke risk. Associations with baseline blood pressure were evaluated with ANCOVA.ResultsDuring the mean ± SD follow-up of 21.2 ± 7.2 y, there were 217 incidences of any stroke: 166 of ischemic stroke and 55 of hemorrhagic stroke. Comparing the highest egg intake quartile with the lowest, the multivariable-adjusted HRs were 0.81 for total stroke (95% CI: 0.54, 1.23; P-trend = 0.32), 0.84 for ischemic stroke (95% CI: 0.53, 1.34; P-trend = 0.44), and 0.75 for hemorrhagic stroke (95% CI: 0.32, 1.77; P-trend = 0.40). The respective HRs for the highest cholesterol intake quartile compared with the lowest were 0.86 (95% CI: 0.57, 1.32; P-trend = 0.42), 0.74 (95% CI: 0.46, 1.20; P-trend = 0.32), and 1.10 (95% CI: 0.45, 2.66; P-trend = 0.75). Diastolic blood pressure was 1.6 mm Hg (P-trend = 0.04) lower in the highest egg intake quartile compared with the lowest, but there were no associations with systolic blood pressure or with cholesterol intake. ApoE phenotype (32% had apoE4 phenotype) did not modify the associations.ConclusionNeither egg nor cholesterol intakes were associated with stroke risk in this cohort, regardless of apoE phenotype.This trial was registered at www.clinicaltrials.gov as NCT03221127.

Verbal Episodic Memory and Endogenous Estradiol: An Association in Patients with Mild Cognitive Impairment and Alzheimer's Disease

In the continuum of patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal controls, a possible association of verbal memory and endogenous estradiol (E2) levels was investigated. Verbal episodic memory was measured with a german version of the California verbal memory test (CVLT). Results were controlled for apolipoprotein E (ApoE) phenotype. We studied 37 controls, 32 MCIs and 117 ADs. Groups differed in all trials of the CVLT and in E2levels . E2 levels differed significantly between groups only among females . In females correcting for age and ApoE, there was an overall correlation between CVLT delayed recall and level of E2 . Stepwise regression analyses found E2level to be a significant predictor for CVLT delayed recall . It may be concluded that lower E2levels occur more in the course of the disease than may be considered as a risk factor per se.

ApoE Polymorphism Is Associated With C-Reactive Protein in Low-HDL Family Members and in Normolipidemic Subjects

The study was aimed to compare inflammatory parameters between carriers of apoE4 isoforms (apoE4/3, apoE4/2, and apoE4/4 phenotypes) and those of carrying apoE3 isoform without apoE4 isoform (apoE3/3 phenotypes and apoE2/3 phenotypes). The concentrations of serum hsCRP, sVCAM-1, sICAM-1, and sE-selectin were measured in 211 subjects from Finnish low-HDL families and in 157 normolipidemic subjects. The subjects with apoE4 isoform had lower concentrations of serum hsCRP both in low-HDL family members (p<0.05) and in normolipidemic subjects (p<0.01). The differences in serum CRP values remained significant after adjustment for age, BMI, smoking status, hypertension, gender, lipoprotein variables, and family number. We conclude that apoE phenotype has a strong influence on serum CRP values.