Context Previous reviews of associations of apolipoprotein E (apoE) genotype and coronary disease have been dominated by smaller studies that are liable to biases.Objective To reassess associations of apoE genotypes with circulating lipid levels and with coronary risk. Data SourcesWe conducted an updated meta-analysis including both published and previously unreported studies, using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database published between January 1970 and January 2007, reference lists of articles retrieved, and a registry of relevant studies. Study SelectionEighty-two studies of lipid levels (86 067 healthy participants) and 121 studies of coronary outcomes (37 850 cases and 82 727 controls) were identified, with prespecified principal focus on studies with at least 1000 healthy participants for lipids and those with at least 500 coronary outcomes.Data Extraction Information on genotype frequencies, lipid levels, coronary outcomes, and laboratory and population characteristics were recorded independently by 2 investigators and/or supplied by study investigators. ResultsIn the most extreme comparison, people with the ε2/ε2 genotype had 1.14 mmol/L (95% confidence interval [CI], 0.87-1.40 mmol/L [44.0 mg/dL; 95% CI; 33.6-51.1 mg/dL]) or about 31% (95% CI, 23%-38%) lower mean lowdensity lipoprotein cholesterol (LDL-C) values than those with the ε4/ε4 genotype. There were approximately linear relationships of apoE genotypes (when ordered ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4) with LDL-C and with coronary risk. The relationship with high-density lipoprotein cholesterol was inverse and shallow and that with triglycerides was nonlinear and largely confined to the ε2/ε2 genotype. Compared with ε3/ε3, the odds ratio for coronary disease was 0.80 (95% CI, 0.70-0.90) in ε2 carriers and was 1.06 (95% CI, 0.99-1.13) in ε4 carriers. ConclusionsThere are approximately linear relationships of apoE genotypes with both LDL-C levels and coronary risk. Compared with individuals with the ε3/ε3 genotype, ε2 carriers have a 20% lower risk of coronary heart disease and ε4 carriers have a slightly higher risk.
We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimer's disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education.
Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.
The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general.
Summary:Purpose: To investigate mortality and especially the incidence of sudden unexpected death in epilepsy (SUDEP) in a population-based cohort of epilepsy surgery patients.Methods: All patients who underwent epilepsy surgery treatment between January 1990 and December 1998 (surgery patients) or whose presurgical evaluation started, although not leading to an operation, during the same period (nonsurgery patients) were identified through the Swedish National Epilepsy register. All subjects were followed up through the Cause of Death Register until December 1998. Standardized mortality ratios (SMRs) for all causes of death and incidence of SUDEP were calculated.Results: During the study period, 651 surgical operations were carried out on 596 patients (316 male). Of those, 14 patients died (six in SUDEP), rendering a total SMR of 4.9 [95% confidence interval (CI), 2.7-8.3]. SUDEP incidence was 2.4 per 1,000 person years. No major differences were found in SMRs or SUDEP rates between subgroups when stratifying for type of operation and for seizure outcome 2 years after surgery. SMR and SUDEP rates were higher in right-sided temporal lobe resections for gliosis than in left-sided, but the number of deaths was small. Among 212 nonsurgery patients, five died (four in SUDEP). The SMR for all causes was 7.9 (2.6-18.4), and SUDEP incidence, 6.3 per 1,000 person years.Conclusions: In this large and strictly population-based cohort, SMR for all causes and SUDEP incidence among surgery patients were similar to those of other studies. No differences in overall mortality emerged by seizure outcome, but none of the SUDEP cases was seizure free at the time of death. Four of five deaths in the nonsurgery group occurred during the surgery evaluation period. Mortality appeared to be lower for surgery than for nonsurgery patients, and the interpretation of this finding is discussed. Key Words: Epilepsy-Mortality-Sudden unexpected death in epilepsy (SUDEP)-Epilepsy surgery.People with epilepsy have an increased mortality rate, in particular, those with more severe epilepsy (1-10). This excess mortality may be related to the underlying cause of epilepsy, as well as being more directly related to the epilepsy and seizures. Sudden unexpected death in epilepsy (SUDEP) is the most important directly epilepsy-related cause of death. The incidence of SUDEP varies between fewer than one per 1,000 person years in population-based studies of incidence cases (3,4) and as high as 10 per 1,000 person years in cohorts of patients with chronic refractory epilepsy, such as epilepsy surgery candidates (7,8,10). This indicates that poor seizure control may increase the risk of SUDEP, a hypothesis confirmed in recent studies of risk factors for SUDEP (10-15). High seizure frequency, polytherapy with antiepileptic drugs (AEDs), and frequent changes of AED dosages have all been shown to increase the risk of SUDEP (11,13). Given that mortality and especially SUDEP seems to be seizure related, it is reasonable to assume that treatment resulting in impr...
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