Immunisation of healthcare workers in the Nordic countries: Variation in recommendations and practices and a lack of assessment

Healthcare workers (HCWs) are at increased risk of both exposure and transmission of infectious disease. Two European Union (EU) directives state that health services are responsible for assessing their employees’ potential exposure to infectious diseases and offering immunisation free of charge. We assessed current policy for immunisation of HCWs and the availability of vaccine coverage data in the Nordic countries by surveying national vaccination experts in Denmark, Finland, Iceland, Norway and Sweden, as well as Swedish county medical officers (CMOs). All national experts and 17 of 21 Swedish CMOs responded. All EU countries had transposed the European directives into national law, while Norway and Iceland had similar national legislation. Recommendations or guidelines were issued in Denmark, Finland, Iceland, Norway and 15 of 17 responding Swedish counties. The range of diseases covered differed by countries and Swedish counties. HCW vaccine coverage data were not systematically collected; incomplete estimates were only available for Finland and two Swedish counties. In conclusion, recommendations or guidelines exist in the Nordic countries, but their impact cannot be assessed, as vaccine uptake among HCWs is not currently measured. Systematic collection of data is a necessary step towards improving HCW immunisation policy and practice in the Nordic countries.     

Interaction of the cholesteryl ester transfer protein I405V polymorphism with alcohol consumption in smoking and non-smoking healthy men, and the effect on plasma HDL cholesterol and apoAI concentration

Three hundred and sixteen healthy Icelandic men and women were examined for the effect of the cholesteryl ester transfer protein (CETP) I405V polymorphism on plasma triglycerides, HDL cholesterol (HDLC) and apoAI concentration. Genotyping was performed using an allele specific oligomelting assay and the frequency of the V allele was 0.31 (95 CI for men 0.23–0.33 and for women 0.29–0.39). In women no significant difference was associated with the V405 genotype for any plasma lipid trait. However, men who were homozygous for the V405 allele had 9% higher apoAI and 14% higher HDLC levels (p < 0.05) than those homozygous for the common 1405 allele. The genotype effect was seen only in the non-smokers (p = 0.07 and <0.05, respectively), and in those consuming alcohol (p < 0.05 for both). Analysis of interaction between the environmental, life-style factors and genotype in men for the traits of HDLC and apoAI showed statistically significant interaction of the genotype only with alcohol consumption. The non-smoking men who reported alcohol consumption and who were homozygous for the CETP V405 allele had 16% higher plasma apoAI concentration than those who carried the 1405 allele, and up to 20% higher apoAI level than smokers. On the basis of prospective studies carried out on the Icelandic population, non-smoking, alcohol-consuming men who are homozygous for the V405 allele could have from 32% to 40% lower risk of having a heart attack.     

Six DNA polymorphisms in the low density lipoprotein receptor gene: their genetic relationship and an example of their use for identifying affected relatives of patients with familial hypercholesterolaemia.

We have determined the relative allele frequency and estimated linkage disequilibrium between six DNA polymorphisms of the low density lipoprotein (LDL) receptor gene. Polymorphisms were detected using the enzymes SfaNI, TaqI, StuI, HincII, AvaII, and NcoI after DNA amplification by the polymerase chain reaction. Strong linkage disequilibrium was detected between many of the pair wise comparisons in a sample of 60 patients heterozygous for familial hypercholesterolaemia (FH). Using the enzymes HincII, NcoI, and SfaNI, 85% of patients were heterozygous for at least one polymorphism and thus potentially informative for cosegregation studies. The polymorphisms were used to follow the inheritance of the defective allele of the LDL receptor gene in the relatives of a patient with FH. Assays of LDL receptor activity on lymphoblastoid cell lines from two members of the family was used to confirm that the proband, but not the hypercholesterolaemic brother, had a defect in the LDL receptor. In the family, none of the children had inherited the allele of the LDL receptor gene inferred to be defective. The problems associated with this cosegregation approach to identify relatives of patients with a clinical diagnosis of FH are discussed.     

APOE ε4 and late-life cognition: mediation by structural brain imaging markers

European Journal of Epidemiology - The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer’s disease....     

Hemodynamics of increased pulse pressure in older women in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study

Pulse pressure increases with advancing age particularly in women. As a result, women have a higher pulse pressure than men from midlife onward. Higher pulse pressure in older women as compared to men is often attributed to increased aortic wall stiffness and premature wave reflection. To evaluate this hypothesis, we measured central aortic input impedance, pulse wave velocity, and wave reflection in 408 older men and women (age range, 69 to 94 yr, mean 75 yr) participating in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik). Women as compared to men had higher pulse pressure (75.8+/-18.7 versus 69.5+/-16.8 mm Hg, P<0.001) and smaller aortic diameters (2.74+/-0.24 versus 2.97+/-0.28 cm, P<0.001). Augmentation index (AI) was higher (11.0+/-15.9 versus 7.9+/-12.9%, P=0.032) in women whereas proximal aortic elastance-wall thickness product (Eh) did not differ (P=0.61). In a stepwise model for pulse pressure that included age and sex and offered aortic diameter, Eh, mean pressure, AI, pulse wave velocity, height, weight, and body surface area as additional covariates, higher pulse pressure was associated with increased wall stiffness, smaller aortic diameter, higher mean pressure, and increased AI (Model R(2)=0.59, P<0.001). The sex difference in pulse pressure (6.6+/-1.7 mm Hg, P<0.001) persisted after Eh entered the model (6.9+/-1.5 mm Hg, P<0.001) but not after aortic diameter entered the model (-0.4+/-1.4 mm Hg, P=0.75). Thus, reduced aortic diameter and impaired matching between diameter and flow accounts for the sex difference in pulse pressure in an unselected community-based cohort of older people.     

Do lipids,blood pressure,diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study

BACKGROUND: Studies on coronary risk factors in men and women are mainly based on mortality data and few compare results of both sexes with consistent study design and diagnostic criteria. This study assesses the major risk factors for coronary events in men and women from the Reykjavik Study. DESIGN: Within a prospective, population-based cohort study individuals without history of myocardial infarction were identified and the relative risk of baseline variables was assessed in relation to verified myocardial infarction or coronary death during follow-up. METHODS: Of the 9681 women and 8888 men who attended risk assessment from 1967-1991, with follow-up period of up to 28 years, 706 women and 1700 men suffered a non-fatal myocardial infarction or coronary death. RESULTS: Serum cholesterol was a significant risk factor for both sexes, with hazard ratios (HR) decreasing with age. Systolic blood pressure was a stronger risk factor for women as was ECG-confirmed left ventricular hypertrophy (women HR 2.89, 95% confidence interval [CI] 1.67-5.01; men HR 1.11 [CI 0.86-1.43]). Fasting blood glucose > or =6.7 mmol/L identified significantly higher risk for women (HR 2.65) than men (HR 2.08) as did self-reported diabetes. Triglyceride risk was significantly higher for women and decreased significantly with age. Smoking increased risk two- to five-fold, increasing with dose, for women, which was significantly higher than the doubling in risk for men. CONCLUSIONS: This large study of the major risk factors compared between the sexes demonstrates similar relative risk of myocardial infarction associated with cholesterol for both sexes, however, the relative risk is higher in women for many other risk factors such as smoking, diabetes, elevated triglycerides and left ventricular hypertrophy.     

Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change

There are no definitive explanations as to why individuals with hypercholesterolemia, a major cardiovascular risk factor, respond differently to dietary change. Fifty five free-living individuals completed a double crossover trial with two dietary regimens, a high saturated fat diet (providing 21% energy from saturated fat and 3% energy from polyunsaturated fat) and a high polyunsaturated fat diet (providing 11% energy as saturated fat and 10% energy as polyunsaturated fat), each phase continuing for 4 weeks. Extensive genotyping and several measures of dietary compliance have provided further insights regarding the determinants of extent of cholesterol response to changes in the nature of dietary fat. Individuals with the CETP B1B1 genotype and the LPL X447+ allele showed an average 0. 44 (95% CI: 0.22, 0.66) and 0.45 (95% CI: 0.18, 0.72) mmol/l greater change in total cholesterol, respectively, than those with one or more CETP B2 allele or homozygous for the LPL S447 allele when comparing diets high and low in saturated fat. Indices of dietary compliance including changes in reported saturated and polyunsaturated fat intake and change in triglyceride linoleate were not significantly different between the CETP genotypes. Change in reported saturated (r=0.36, P=0.04) and polyunsaturated (r=0.22, P=0. 05) fat intake and change in triglyceride linoleate (reflecting polyunsaturated fat intake) (r=0.21, P=0.07), also predicted total cholesterol response to dietary fat changes. In multivariate analyses, variation in the cholesterol ester transfer protein and lipoprotein lipase genes predicted response independent of measures of dietary compliance, suggesting that these two genes are important determinants of variation in cholesterol response to dietary change in free-living individuals.     

Mediation Analysis of Aortic Stiffness and Renal Microvascular Function

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular–microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72–92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=−2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, −1.35 to −0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, −2.22 to −0.40; 95% confidence interval of indirect effect including renal vascular resistance, −2.51 to −0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.