Burden of neurodegenerative diseases in the Eastern Mediterranean Region, 1990-2016: findings from the Global Burden of Disease Study 2016.

BACKGROUND AND PURPOSE: The Eastern Mediterranean Region (EMR) is experiencing a demographic shift towards rapid aging at a time of political unrest. We aimed to estimate the burden of neurodegenerative disorders and its relationship with sociodemographic index in the EMR countries from 1990 to 2016. METHODS: Using data from the Global Burden of Disease Study 2016, we calculated country-specific trends for prevalence, mortality, disability-adjusted life-years (DALY), years of life lost and years lived with disability (YLD) for Alzheimer's disease/other dementias and Parkinson's disease in the EMR during 1990-2016. RESULTS: In the EMR, the age-standardized prevalence rate of Alzheimer's disease/other dementias and Parkinson's disease was estimated at 759.8/100 000 (95% uncertainty intervals, 642.9-899.9) and 87.1/100 000 (95% uncertainty intervals, 69.8-108.2) people in 2016, demonstrating 0.01% and 42.3% change from 1990, respectively. Neurodegenerative disorders contributed to 5.4% of total DALY and 4.6% of total YLD among the older EMR population (70 years of age or older in 2016). Age-standardized DALY due to Parkinson's disease were strongly correlated with the sociodemographic index level (r = 0.823, P < 0.001). The YLD:DALY ratio of neurodegenerative diseases declined during this period in the low-income but not the high-income EMR countries. CONCLUSIONS: Our findings demonstrated an increasing trend in the burden of dementias and Parkinson's disease in most EMR countries between 1990 and 2016. With aging of the EMR populations, countries should target the modifiable risk factors of neurodegenerative diseases to control their increasing burden.

Association of plasma neopterin with risk of an inpatient hospital diagnosis of atrial fibrillation: results from two prospective cohort studies.

BACKGROUND: Link between inflammation and atrial fibrillation (AF) has been increasingly recognized. Neopterin, a biomarker of cellular immune activation, may be associated with incident AF. OBJECTIVE: To investigate the association between plasma neopterin levels and risk of an inpatient hospital diagnosis of AF, and to evaluate a joint association of neopterin and a nonspecific inflammatory marker C-reactive protein (CRP) in two prospective cohorts. METHODS: We performed a prospective analysis from a community-based cohort (the Hordaland Health Study (HUSK), n = 6891), and validated the findings in a cohort of patients with suspected stable angina pectoris (the Western Norway Coronary Angiography Cohort (WECAC), n = 2022). RESULTS: In both cohorts, higher plasma levels of neopterin were associated with an increased risk of incident AF after adjustment for age, sex, body mass index, current smoking, diabetes, hypertension and renal function. The multivariable-adjusted hazard ratio (HR) (95% CI) per one SD increment of log-transformed neopterin was 1.20 (1.10-1.32) in HUSK and 1.26 (1.09-1.44) in WECAC. Additional adjustment for CRP did not materially affect the risk association for neopterin. The highest risk of AF was found among individuals with both neopterin and CRP levels above the median (HR: 1.54; 95% CI: 1.16-2.05 in HUSK and HR: 1.67; 95% CI: 1.11-2.52 in WECAC). CONCLUSIONS: Our findings indicate an association of plasma neopterin with risk of an inpatient hospital diagnosis of AF, which remains after adjustment for traditional risk factors as well as for CRP. This study highlights a role of cellular immune activation, in addition to inflammation, in AF pathogenesis.

Smoking, plasma cotinine and risk of atrial fibrillation: the Hordaland Health Study.

BACKGROUND: Cigarette smoking has been identified as a major modifiable risk factor for coronary heart disease and mortality. However, findings on the relationship between smoking and atrial fibrillation (AF) have been inconsistent. Furthermore, findings from previous studies were based on self-reported smoking. OBJECTIVE: To examine the associations of smoking status and plasma cotinine levels, a marker of nicotine exposure, with risk of incident AF in the Hordaland Health Study. METHODS: We conducted a prospective analysis of 6682 adults aged 46-74 years without known AF at baseline. Participants were followed via linkage to the Cardiovascular Disease in Norway (CVDNOR) project and the Cause of Death Registry. Smoking status was assessed by both questionnaire and plasma cotinine levels. RESULTS: A total of 538 participants developed AF over a median follow-up period of 11 years. Using questionnaire data, current smoking (HR: 1.41, 95% CI: 1.09-1.83), but not former smoking (HR: 1.03, 95% CI: 0.83-1.28), was associated with an increased risk of AF after adjustment for gender, age, body mass index, hypertension, physical activity and education. Using plasma cotinine only, the adjusted HR (95% CI) was 1.40 (1.12-1.75) for participants with cotinine ≥85 nmol L-1 compared to those with cotinine <85 nmol L-1 . However, the risk increased with elevated plasma cotinine levels until 1199 nmol L-1 (HR: 1.55, 95% CI: 1.16-2.05 at the third group vs. the reference group) and plateaued at higher levels. CONCLUSIONS: Current, but not former smokers, had a higher risk of developing AF. Use of plasma cotinine measurement corroborated this finding.

Association between Weight Change and Mortality in Community Living Older People Followed for Up to 14 Years. The Hordaland Health Study (HUSK).

OBJECTIVES: To study the importance of weight change with regard to mortality in older people. DESIGN: Prospective cohort study. PARTICIPANTS: The cohort includes participants in the Hordaland Health Study, Norway, 1997-99 (N=2935, age 71-74 years) who had previously participated in a survey in 1992-93. MEASUREMENTS: Participants with weight measured at both surveys were followed for mortality through 2012. Cox proportional hazards models were used to calculate risk of death according to changes in weight. Hazard ratios (HR) with 95% confidence intervals (CIs) for people with stable weight (± <5% weight change) were compared to people who lost (≥5%) or gained (≥5%) weight. Cox regression with penalized spline was used to evaluate the association between weight change (in kg) and mortality. Analyses were adjusted for age, sex, physical activity, smoking, diabetes, hypertension, and previous myocardial infarction or stroke. Participants with cancer were excluded. RESULTS: Compared to those with stable weight, participants who lost ≥5% weight had an increased mortality risk (HR 1.59 [95% CI: 1.35-1.89]) while the group with weight gain ≥5% did not (HR 1.07 [95% CI 0.90-1.28]). Penalized spline identified those who lost more than about three kg or gained more than about 12 kg as having increased risk of death. CONCLUSION: Even a minor weight loss of ≥5% or >3 kg were significantly associated with increased risk of mortality. Thus, weight should be routinely measured in older adults.

Plasma dimethylglycine, nicotine exposure and risk of low bone mineral density and hip fracture: the Hordaland Health Study.

UNLABELLED: In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine. INTRODUCTION: Dimethylglycine (DMG) is a product of the choline oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plasma DMG in bone health is unknown. METHODS: We studied the associations of plasma DMG with BMD among 5315 participants (46-49 and 71-74 years old) and with hip fracture among 3310 participants (71-74 years old) enrolled in the Hordaland Health Study. RESULTS: In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.43-1.99). The association was stronger in participants exposed compared to those unexposed to nicotine (OR 2.31, 95% CI 1.73-3.07 and OR 1.43, 95% CI 1.16-1.75, respectively, p interaction = 0.008). In the older cohort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio [HR] 1.70, 95% CI 1.28-2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95% CI 1.40-8.28). CONCLUSION: Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention.

Trends in 28-day and 1-year mortality rates in patients hospitalized for a first acute myocardial infarction in Norway during 2001-2009: a "Cardiovascular disease in Norway" (CVDNOR) project.

OBJECTIVE: The aim of this study was to investigate the trends in 28-day and 1-year mortality rates in patients hospitalized for a first acute myocardial infarction (AMI) in Norway during the period 2001-2009. Potential age group and gender differences in these trends were also examined. DESIGN, SUBJECTS AND SETTING: In this retrospective nationwide cohort study, patients hospitalized for a first AMI between 2001 and 2009 were identified in the Cardiovascular Disease in Norway 1994-2009 (CVDNOR) project and followed for 1 year. MAIN OUTCOME MEASURES: Trends in 28-day and 1-year mortality [both all-cause and cardiovascular disease (CVD) mortality] were investigated. RESULTS: A total of 115,608 patients (60.6% men) were hospitalized for a first AMI during the study period. Mortality at 28 days was reduced annually by 3.8% overall and by 6.7%, 4.1% and 2.6% in patients aged 25-64, 65-84 and ≥85 years, respectively (all Ptrend < 0.001). In addition, 1-year all-cause mortality was reduced annually by 2.0% overall (Ptrend < 0.001) and by 3.7% (Ptrend = 0.02), 2.5% (Ptrend < 0.001) and 1.1% (Ptrend < 0.001) in patients aged 25-64, 65-84 and ≥85 years, respectively. Furthermore, 1-year CVD mortality was reduced overall by 6.2% annually; a reduction was observed in all age groups. Finally, 1-year non-CVD mortality increased annually overall by 3.9% due to an increase in patients aged ≥65 years. CONCLUSION: Mortaity at 28 days after the first AMI declinedin Norway between 2001 and 2009 in both men and women and in all age groups. All-cause mortality at 1 year also declined both in men and women due to decreases in CVD mortality rates, whilst non-CVD mortality rates increased amongst patients ≥65 years of age.

Plasma methionine, choline, betaine, and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Disturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. PATIENTS AND METHODS: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations. RESULTS: Overall, methionine (OR: 0.79, 95% CI: 0.63-0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60-0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66-1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50-1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43-0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk. CONCLUSIONS: Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC.

Plasma sulfur amino acids and stearoyl-CoA desaturase activity in two Caucasian populations.

In rats, dietary restriction of the cysteine precursor methionine suppresses hepatic stearoyl-CoA desaturase (SCD)-1 expression and activity, whereas cysteine supplementation reverses these effects. In 2 independent cohorts: Hordaland Health Study (HUSK; N=2021, aged 71-74y), Norway, and Hoorn study (N=686, aged 50-87y), Netherlands, we examined the cross-sectional associations of plasma sulfur-containing compounds (SCC; methionine, S-adenosylmethionine, S-adenosylhomocysteine, homocysteine, cystathionine, total cysteine (tCys), glutathione and cysteinylglycine) with SCD-16 index (16:1n-7/16:0), estimated from fatty acid profiles of total plasma or serum lipids. Only tCys was consistently associated with SCD-16 index after adjustments for sex and age (HUSK: partial r=0.14; Hoorn: partial r=0.11, P<0.001 for both), and after further adjustments for other SCC, body fat, diet, exercise and plasma lipids (HUSK: partial r=0.07, P=0.004; Hoorn: partial r=0.12, P=0.013). Together with animal data showing an effect of dietary cysteine on SCD1, our results suggest a role for cysteine in SCD1 regulation in humans.

A community-based study on determinants of circulating markers of cellular immune activation and kynurenines: the Hordaland Health Study.

Circulating neopterin and kynurenine/tryptophan ratio (KTR) increase during inflammation and serve as markers of cellular immune activation, but data are sparse on other determinants of these markers and metabolites of the kynurenine pathway. We measured neopterin, tryptophan, kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid in plasma in two age groups, 45-46 years (n = 3723) and 70-72 years (n = 3329). Differences across categories of the potential determinants, including age, gender, renal function, body mass index (BMI), smoking and physical activity, were tested by Mann-Whitney U-test and multiple linear regression including age group, gender, renal function and lifestyle factors. In this multivariate model, neopterin, KTR and most kynurenines were 20-30% higher in the older group, whereas tryptophan was 7% lower. Men had 6-19% higher concentrations of tryptophan and most kynurenines than women of the same age. Compared to the fourth age-specific estimated glomerular filtration rate (eGFR) quartile, the first quartile was associated with higher concentrations of neopterin (25%) and KTR (24%) and 18-36% higher concentrations of kynurenines, except 3-hydroxyanthranilic acid. Additionally, KTR, tryptophan and all kynurenines, except anthranilic acid, were 2-8% higher in overweight and 3-17% higher in obese, than in normal-weight individuals. Heavy smokers had 4-14% lower levels of tryptophan and most kynurenines than non-smokers. Age and renal function were the strongest determinants of plasma neopterin, KTR and most kynurenines. These findings are relevant for the design and interpretation of studies investigating the role of plasma neopterin, KTR and kynurenines in chronic diseases.

Perinatal and infant mortality in term and preterm births among women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to estimate the risks of adverse birth outcomes such as stillbirth, infant death, preterm birth and pre-eclampsia in women with type 1 diabetes, compared with the background population. We further aimed to explore the risks of adverse birth outcomes in preterm and term deliveries separately. METHODS: By linkage of two nationwide registries, the Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry, we identified 1,307 births among women with pregestational type 1 diabetes registered in the Diabetes Registry, and 1,161,092 births in the background population during the period 1985-2004. The ORs with 95% CIs for adverse outcome among women with type 1 diabetes vs the background population were estimated using logistic regression. RESULTS: The OR for stillbirth (≥22 weeks of gestation) was 3.6 (95% CI 2.5, 5.3), and for perinatal death (stillbirth or death in the first week of life) it was 2.9 (95% CI 2.0, 4.1). The OR for infant death (first year of life) was 1.9 (95% CI 1.1, 3.2). For preterm birth (< 37 weeks of gestation) and pre-eclampsia the ORs were 4.9 (95% CI 4.3, 5.5) and 6.3 (95% CI 5.5, 7.2), respectively. When preterm and term deliveries were analysed separately, the excess risk of stillbirth and infant death in women with diabetes was confined to term deliveries. CONCLUSIONS/INTERPRETATION: Pregestational type 1 diabetes was associated with a considerably higher risk of adverse pregnancy outcomes, including infant death, compared with the background population. A novel finding of the study was that the increased risk was confined to term births.

Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials.

OBJECTIVES: In the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, patients were randomly assigned to homocysteine-lowering B-vitamins or no such treatment. We investigated their effects on cardiovascular outcomes in the trial populations combined, during the trials and during an extended follow-up, and performed exploratory analyses to determine the usefulness of homocysteine as a predictor of cardiovascular outcomes. DESIGN: Pooling of data from two randomized controlled trials (1998-2005) with extended post-trial observational follow-up until 1 January 2008. SETTING: Thirty-six hospitals in Norway. SUBJECTS: 6837 patients with ischaemic heart disease. INTERVENTIONS: One capsule per day containing folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg), or folic acid plus vitamin B12, or vitamin B6 alone or placebo. MAIN OUTCOME MEASURES: Major adverse cardiovascular events (MACEs; cardiovascular death, acute myocardial infarction or stroke) during the trials and cardiovascular mortality during the extended follow-up. RESULTS: Folic acid plus vitamin B12 treatment lowered homocysteine levels by 25% but did not influence MACE incidence (hazard ratio, 1.07; 95% CI, 0.95-1.21) during 39 months of follow-up, or cardiovascular mortality (hazard ratio, 1.12; 95% CI, 0.95-1.31) during 78 months of follow-up, when compared to no such treatment. Baseline homocysteine level was not independently associated with study outcomes. However, homocysteine concentration measured after 1-2 months of folic acid plus vitamin B12 treatment was a strong predictor of MACEs. CONCLUSION: We found no short- or long-term benefit of folic acid plus vitamin B12 on cardiovascular outcomes in patients with ischaemic heart disease. Our data suggest that cardiovascular risk prediction by plasma total homocysteine concentration may be confined to the homocysteine fraction that does not respond to B-vitamins.

Medium- and long-term performance of 11,516 uncemented primary femoral stems from the Norwegian arthroplasty register.

Primary uncemented femoral stems reported to the Norwegian arthroplasty register between 1987 and 2005 were included in this prospective observational study. There were 11 516 hips (9679 patients) and 14 different designs of stem. Kaplan-Meier survival probabilities and Cox regression were used to analyse the data. With aseptic loosening as the end-point, all currently used designs performed excellently with survival of 96% to 100% at ten years. With the end-point as stem revision for any cause, the long-term results of the different designs varied from poor to excellent, with survival at 15 years ranging between 29% and 97%. Follow-up for longer than seven years was needed to identify some of the poorly-performing designs. There were differences between the stems; the Corail, used in 5456 hips, was the most frequently used stem with a survival of 97% at 15 years. Male gender was associated with an increased risk of revision of x 1.3 (95% confidence interval 1.05 to 1.52), but age and diagnosis had no influence on the results. Overall, modern uncemented femoral stems performed well. Moderate differences in survival between well-performing stems should be interpreted with caution since the differences may be caused by factors other than the stem itself.

Homocysteine-lowering therapy does not affect inflammatory markers of atherosclerosis in patients with stable coronary artery disease.

OBJECTIVES: A high level of total homocysteine (tHcy) is a risk marker for cardiovascular disease (CVD), and is related to inflammation. We wanted to test the effect of homocysteine-lowering B-vitamin therapy, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on inflammatory markers associated with atherosclerosis. DESIGN: Single centre, prospective double-blind clinical interventional study, randomised in a 2 x 2 factorial design. SUBJECTS AND METHODS: Ninety patients (21 female) with suspected coronary artery disease (CAD), aged 38-80 years, were blindly randomised into one of four groups of daily oral treatment with (A) folic acid (0.8 mg)/vitamin B12 (0.4 mg)/vitamin B6 (40 mg), (B) folic acid/vitamin B12, (C) vitamin B6 alone or (D) placebo. Blood samples were collected before and after 6 months of treatment. RESULTS: Before intervention, median levels of the analytes were: tHcy 11.0 micromol L(-1), neopterin 8.1 nmol L(-1), soluble CD40 ligand (sCD40L) 3.9 ng mL(-1), interleukin (IL)-6 1.9 pg mL(-1), C-reactive protein (CRP) 1.9 mg L(-1) and low-density lipoprotein (LDL) cholesterol 3.3 mmol L(-1). tHcy was significantly associated with neopterin (r = 0.49, P < 0.001) and with IL-6 (r = 0.29, P = 0.01), but not with CRP or sCD40L. Neither treatment with folic acid/B12 nor with B6 induced significant changes in any of these inflammatory biomarkers (P >or= 0.14). In patients receiving folic acid/B12 (groups A and B), tHcy was reduced with 33% (P < 0.001). CONCLUSIONS: In patients with stable CAD, homocysteine-lowering therapy with B-vitamins does not affect levels of inflammatory markers associated with atherogenesis. Failure to reverse inflammatory processes, may partly explain the negative results in clinical secondary B-vitamin intervention trials.

Failure mechanisms after unicompartmental and tricompartmental primary knee replacement with cement.

BACKGROUND: Concern exists regarding the durability of unicompartmental knee replacements. The purpose of the present study was to compare the early failure rates and failure mechanisms of primary cemented unicompartmental knee replacements with those of primary cemented tricompartmental total knee replacements. METHODS: The rates of failure of primary cemented unicompartmental knee replacements (n = 2288) and tricompartmental total knee replacements (n = 3032) as reported to the Norwegian Arthroplasty Register from January 1994 through December 2004 were compared with use of Kaplan-Meier estimated survival rates and Cox multiple regression. RESULTS: The ten-year survival probability was 80.1% (95% confidence interval, 76.0% to 84.2%) for unicompartmental knee replacements, compared with 92.0% (95% confidence interval, 90.4 to 93.6%) for total knee replacements, with a relative risk of revision of 2.0 (95% confidence interval, 1.6 to 2.5) (p < 0.001). This increased risk of revision following unicompartmental knee replacement was seen in all age-categories. Unicompartmental knee replacement was associated with an increased risk of revision due to pain (relative risk, 11.3 [95% confidence interval, 4.8 to 26.8]; p < 0.001), aseptic loosening of the tibial component (relative risk, 1.9 [95% confidence interval, 1.2 to 3.0]; p = 0.01) and of the femoral component (relative risk, 4.8 [95% confidence interval, 2.3 to 10.3]; p < 0.001), and periprosthetic fracture (relative risk, 3.2 [95% confidence interval, 1.2 to 8.9]; p = 0.02) as compared with total knee replacement. Unicompartmental knee replacement was associated with a lower risk of infection compared with total knee replacement (relative risk, 0.28 [95% confidence interval, 0.10 to 0.74]; p = 0.01). CONCLUSIONS: The survival of cemented unicompartmental knee replacements is inferior to that of cemented tricompartmental total knee replacements in all age-categories.

Apolipoprotein E epsilon4 and impaired episodic memory in community-dwelling elderly people: a marked sex difference. The Hordaland Health Study.

BACKGROUND: Among elderly people without dementia, the apolipoprotein E epsilon4 allele (APOE4) has been associated with cognitive deficit, particularly in episodic memory, but few reports are available on whether this association differs by sex. METHODS: In a community-dwelling Norwegian cohort of 2181 elderly people (55% women), aged 70-74 years, episodic memory was examined in relation to sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT). RESULTS: Possession of at least one APOE4 allele had a modest, detrimental effect on episodic memory in women, whereas in men, heterozygotes were unaffected and homozygotes had markedly lower scores across the distribution of KOLT scores. This sex difference was found consistently in all analyses: on comparing means and medians, examining trends across quintiles, and studying the distribution of scores and the risk of cognitive impairment. Results were broadly similar when adjusted for known determinants of cognition and also when severely impaired participants were excluded. The adjusted odds ratio (OR) of cognitive impairment in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for homozygotes. CONCLUSIONS: Although the harmful effect of APOE4 on episodic memory was modest in women, the risk was found to occur in about 30%. APOE4 was observed to have a dramatic effect on episodic memory in men, but only in homozygotes, who comprised about 3% of men: the whole male homozygous group showed a marked shift to lower memory scores.

Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland Homocysteine Study.

BACKGROUND: The factor V Leiden (FVL) mutation is the most common cause of inherited thrombophilia in Caucasian populations, and women with this variant allele are at increased risk for pregnancy complications. AIM: To examine whether the FVL allele is associated with pregnancy complications and adverse outcomes in a population-based study, and to identify potential factors that interact with the FVL genotype. DESIGN: Retrospective cohort study in a geographically-defined area. METHODS: Polymorphisms of factor V 1691G-->A, methylenetetrahydrofolate reductase (MTHFR) 677C --> T and 1298A --> C and plasma levels of total homocysteine, folate and vitamin B(12) were determined in blood samples collected in 1992-1993 from 5874 women aged 40-42 years, and linked with 14 474 pregnancies in the same women, recorded in the Medical Birth Registry of Norway, 1967-1996. RESULTS: The allelic frequency of FVL was 3.7% (6.9% heterozygotes, 0.3% homozygotes). Maternal FVL mutation was associated with significantly higher risks of pre-eclampsia (OR 1.63, 95%CI 1.15-2.30), pre-eclampsia at <37 weeks (OR 2.76, 1.34-5.70), low birth weight (OR 1.34, 95%CI 1.03-1.74) and stillbirth (OR 2.20, 95%CI 1.45-3.36). The presence of a variant allele for the 677C --> T MTHFR polymorphism strengthened the association between FVL and stillbirth (OR 3.34, 95%CI 1.95-5.73) (p(interaction) = 0.034). DISCUSSION: FVL mutation is a significant risk factor for pregnancy complications and adverse outcomes, and MTHFR 677CT/TT genotype can further enhance the risk of stillbirth.

Failure rates for 4762 revision total hip arthroplasties in the Norwegian Arthroplasty Register.

We present the results for 4762 revision total hip arthroplasties with no previous infection in the hip, which were reported to the Norwegian Arthroplasty Register between 1987 and 2003. The ten-year failure rate for revised prostheses was 26% (95% CI 25 to 26). Cox regression analyses were undertaken separately for acetabular and femoral revision components. Cemented revision components without allograft was the reference category. For acetabular components, we found a significantly reduced risk of failure for uncemented revisions both with (relative risk (RR) = 0.66; 95% CI 0.43 to 0.99) and without (RR = 0.37; 95% CI 0.22 to 0.61) allograft. For femoral components, we found a significantly reduced risk of failure for uncemented revisions, both with (RR = 0.27; 95% CI 0.16 to 0.46) and without (RR = 0.22; 95% CI 0.11 to 0.46) unimpacted allograft. This reduced risk of failure also applied to cemented revision components with allograft (RR = 0.53; 95% CI 0.33 to 0.84) and with impaction bone grafting (RR = 0.34; 95% CI 0.19 to 0.62). Revision prostheses have generally inferior results when compared with primary prostheses. Recementation without allograft, and uncemented revision with bone impaction, were associated with worse results than the other revision techniques which we studied.

Distribution and determinants of serum creatinine in the general population: the Hordaland Health Study.

BACKGROUND: Serum creatinine is a well-recognized risk factor for cardiovascular disease (CVD) and is also a rough measure of glomerular filtration rate. The purpose of the present study was to investigate determinants of serum creatinine in the general population. METHODS: The participants were recruited as a part of the Hordaland Health Study, and included 6952 men aged 41-49 years, 8218 women aged 41-49 years, 1470 men aged 71-74 years and 1865 women aged 71-74 years. Data on lifestyle factors, medical history and medication were obtained through questionnaires. Body size and blood pressure measurements as well as non-fasting blood samples were obtained during a health examination. Determinants of serum creatinine were identified using multiple linear and logistic regression analyses. RESULTS: Male and older participants had higher levels of serum creatinine than female and middle-aged participants. For older participants, creatinine was associated with serum triglycerides, CVD, upper-arm circumference and use of antihypertensive drugs as well as inversely associated with cigarette smoking. For middle-aged participants, creatinine was associated with upper-arm circumference, serum lipids and physical exercise, as well as inversely associated with smoking and alcohol intake. The associations with CVD risk factors were much stronger for older participants than for middle-aged participants and most associations were significant after adjustments as well as present within the reference range of serum creatinine. CONCLUSIONS: In this general population sample, high serum creatinine levels were associated with risk factors for CVD. These associations were stronger in older subjects, whereas in middle-aged subjects lifestyle variables were relatively more important.

Homocysteine and its relation to B-vitamins in Graves' disease before and after treatment: effect modification by smoking.

OBJECTIVES: To investigate plasma total homocysteine levels and its relation to B-vitamins and smoking in Graves' disease before and after antithyroid therapy. DESIGN: A longitudinal study taking place at four hospitals in Norway. METHODS AND SUBJECTS: Plasma total homocysteine, serum folate, serum cobalamin and riboflavin, flavin mononucleotide and flavin adenine dinucleotide in plasma were investigated in 182 patients with hyperthyroidism before treatment. The same parameters were reinvestigated in 112 of these patients after attaining euthyroid state. RESULTS: In hyperthyroidism, plasma total homocysteine was low, and inversely related to folate, cobalamin and riboflavin, and positively related to serum creatinine and age. Following antithyroid therapy, total homocysteine increased and the concentration of folate, cobalamin, riboflavin, flavin mononucleotide and flavin adenine dinucleotide decreased significantly. The most pronounced reduction (35%) was observed for flavin mononucleotide. In the hyperthyroid state, smokers had lower levels of folate and flavin mononucleotide than non-smokers. After restoration of euthyroidism, both folate and riboflavin were significantly lower in smokers than non-smokers. Plasma total homocysteine increased according to decreasing quartiles of B-vitamins. For riboflavin, this relation was confined to smokers. CONCLUSION: Plasma total homocysteine changes according to thyroid status. These changes may be partly attributable to altered folate, cobalamin but also riboflavin status, particularly in smokers.