Snorri Bjorn Rafnsson

Cognitive decline and markers of inflammation and hemostasis: The Edinburgh Artery Study

OBJECTIVES: To determine whether circulating markers of activated inflammation and hemostasis are associated with cognitive decline in older people.

Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality

Objective Sepsis is a complex and hard-to-define condition with many different interactions with other disorders. Presently, there are no estimates of the burden of sepsis and septicaemia at the global level and it was not included in the initial Global Burden of Disease study. Non-maternal sepsis has only recently received attention as a substantial global public health problem. The aim of this study was to assess available data on the burden of non-maternal sepsis, severe sepsis and septic shock in the community and to identify key gaps in information needed to estimate the global burden of sepsis. Methods Literature review of English language-based studies reporting on the incidence, prevalence, mortality or case-fatality of sepsis, severe sepsis and septic shock. The available literature was searched using the MEDLINE database of citations and abstracts of biomedical research articles published between 1980 and 2008. Findings 8 studies reported incidence of sepsis, severe sepsis or septic shock at the national level (4 from the USA and 1 from Brazil, the UK, Norway and Australia). No studies on the incidence, prevalence, mortality or case-fatality from sepsis in developing countries were found. The population sepsis incidence ranged from 22 to 240/100 000 (most plausible estimates ranged from 149 to 240/100 000); of severe sepsis from 13 to 300/100 000 (most of the estimates were between 56 and 91/100 000); and of septic shock 11/100 000. Case-fatality rate depends on the setting and severity of disease. It can reach up to 30% for sepsis, 50% for severe sepsis and 80% for septic shock. While the data were compiled using strict inclusion and exclusion criteria, a degree of uncertainty still exists regarding the reported estimates. Conclusion The few national-level reports available allow only a very crude estimation of the incidence of sepsis in developed countries while there is apparent lack of data from developing countries. A clear and universal definition of sepsis as well as the development of a sound epidemiological framework to begin addressing the magnitude of this problem is urgently needed through research in developing countries.

Large-scale epidemiological data on cardiovascular diseases and diabetes in migrant and ethnic minority groups in Europe.

BACKGROUND Data on differences by ethnicity in cardiovascular diseases (CVDs) and diabetes, reflecting the influence of diverse cultural, social and religious factors, are important to providing clues to disease aetiology and directing public health interventions and health care resources. METHODS Through a network of European public health researchers and searches of bibliographic databases and internet sites, we determined the availability and characteristics of ethnically relevant data on mortality and morbidity from coronary heart disease (CHD), stroke and diabetes, in current European Union countries; data from the four countries comprising the UK were assessed separately. RESULTS In total, 25 countries had one or more relevant data sets (72 in total); however, two-thirds (n = 47) of the data sources came from only eight Nordic and Western European countries. For several countries, no data could be identified. Ethnically relevant, national death registers were available in 24 countries. Country of birth was the most common indicator of ethnicity. Data on CHD, stroke and diabetes morbidity among migrant and ethnic minority populations are currently scarce; both between and within countries, there are important differences in how ethnicity as well as disease outcomes are defined and measured which limits data comparability. CONCLUSION Reliable routine data are key to evidence-based public health policies at both national and EU level. EU countries have a relatively weak base for assessing needs and planning health care interventions for its migrant and ethnic minority populations. The lack of ethnically relevant data on CVD and diabetes across the EU needs to be addressed urgently.

Cardiovascular Diseases and Decline in Cognitive Function in an Elderly Community Population: The Edinburgh Artery Study

Objective: To investigate cognitive performance and 4-year change in cognitive function in relation to different clinical manifestations of atherosclerotic disease in an elderly community population. Methods: The Edinburgh Artery Study is a population cohort study of men and women who were recruited to a baseline survey in 1987 and 1988. From the time of study entry, the participants have been invited to two follow-up clinical examinations and continuously monitored for major fatal and nonfatal vascular events. All alive and eligible subjects were invited for cognitive testing in two study years when the mean age of the sample was 73.1 (standard deviation = 5.0) years. A follow-up cognitive assessment was performed in 2002 and 2003 on 452 survivors. Results: In multivariate analyses controlling for demographic characteristics, depression, and major atherosclerotic risk factors, stroke was associated with a significantly worse performance on tests of verbal memory (p = .02) and letter fluency (p = .002). In addition, stroke was related to a significantly steeper 4-year decline in verbal memory performance (p = .04). Among the subjects who had not had an overt stroke, those with symptomatic peripheral arterial disease experienced a significantly greater 4-year decline in verbal memory functioning (p = .04). Conclusions: In older people, stroke is associated with both worse performance on cognitive tests and progressive verbal memory decline. Elderly individuals with vascular diseases other than stroke may also be vulnerable to a greater decline in verbal memory function. A relationship between vascular diseases and verbal memory decline may exist independently of depressed mood and major atherosclerotic risk factors. CVD = cardiovascular disease; PAD = peripheral arterial disease; IC = intermittent claudication; MI = myocardial infarction; WHO = World Health Organization; ECG = electrocardiogram; MRI = magnetic resonance imaging; LMT = logical memory test; RPM = Raven’s progressive matrices; VFT = verbal fluency test; DST = digit symbol test; NART = national adult reading test; GCF = general cognitive factor; SD = standard deviation; MMSE = mini-mental state examination; CHD = coronary heart disease; SBP = systolic blood pressure.

Peripheral arterial disease and cognitive function.

Abstract As a marker of generalized atherosclerosis, peripheral arterial disease (PAD) has implications not only for the affected lower extremity but also to overall cardiovascular health. It confers an increased risk of non-fatal and fatal vascular events which increases with the severity of the disease. Patient-based studies have shown that individuals with advanced PAD tend to perform poorly on cognitive tests compared to controls. In population studies, PAD is associated with an increased cognitive decline independently of previous cerebrovascular disease and cardiovascular risk factors. A low ankle–brachial index (ABI) may be an early predictor of cognitive decline and of potential value in identifying individuals at increased risk of cognitive impairment. In patients with PAD, secondary preventive measures directed at decreasing the long-term systemic vascular complications may also be important to the preservation of cognitive health. However, evidence suggests that PAD patients may be undertreated with regard to atherosclerotic risk factors, as demonstrated by an undue emphasis on symptom relief rather than essential risk factor reduction. More research needs to be carried out to determine the predictors of cognitive function in PAD patients, whether subtle cognitive disturbances are related to activities of daily living, including medical treatment compliance, and whether neuroprotective strategies and atherosclerotic risk factor control positively influence cognitive function in these high-risk patients.

Mortality from circulatory diseases by specific country of birth across six European countries: Test of concept

BACKGROUND Important differences in cardiovascular disease (CVD) mortality by country of birth have been shown within European countries. We now focus on CVD mortality by specific country of birth across European countries. METHODS For Denmark, England and Wales, France, The Netherlands, Scotland and Sweden mortality information on circulatory disease, and the subcategories of ischaemic heart disease, and cerebrovascular disease, was analysed by country of birth. Information on population was obtained from census data or population registers. Directly age-standardized rates per 100 000 were estimated by sex for each country of birth group using the WHO World Standard population 2000-25 structure. For differences in the results, at least one of the two 95% confidence intervals did not overlap. RESULTS Circulatory mortality was similar across countries for men born in India (355.7 in England and Wales, 372.8 in Scotland and 244.5 in Sweden). For other country of birth groups-China, Pakistan, Poland, Turkey and Yugoslavia-there were substantial between-country differences. For example, men born in Poland had a rate of 630.0 in Denmark and 499.3 in England and Wales and 153.5 in France; and men born in Turkey had a rate of 439.4 in Denmark and 231.4 in The Netherlands. A similar pattern was seen in women, e.g. Poland born women had a rate of 264.9 in Denmark, 126.4 in England and Wales and 54.4 in France. The patterns were similar for ischaemic heart disease mortality and cerebrovascular disease mortality. CONCLUSION Cross-country comparisons are feasible and the resulting findings are interesting. They merit public health consideration.

Migrant mortality from diabetes mellitus across Europe: the importance of socio-economic change

The first objective of this study was to determine and quantify variations in diabetes mortality by migrant status in different European countries. The second objective was to investigate the hypothesis that diabetes mortality is higher in migrant groups for whom the country of residence (COR) is more affluent than the country of birth (COB). We obtained mortality data from 7 European countries. To assess migrant diabetes mortality, we used direct standardization and Poisson regression. First, migrant mortality was estimated for each country separately. Then, we merged the data from all mortality registers. Subsequently, to examine the second hypothesis, we introduced gross domestic product (GDP) per capita of COB in the models, as an indicator of socio-economic circumstances. The overall pattern shows higher diabetes mortality in migrant populations compared to local-born populations. Mortality rate ratios (MRRs) were highest in migrants originating from either the Caribbean or South Asia. MRRs for the migrant population as a whole were 1.9 (95% CI 1.8–2.0) and 2.2 (95% CI 2.1–2.3) for men and women respectively. We furthermore found a consistently inverse association between GDP of COB and diabetes mortality. Most migrant groups have higher diabetes mortality rates than the local-born populations. Mortality rates are particularly high in migrants from North Africa, the Caribbean, South Asia or low-GDP countries. The inverse association between GDP of COB and diabetes mortality suggests that socio-economic change may be one of the key aetiological factors.

Sizable variations in circulatory disease mortality by region and country of birth in six European countries

BACKGROUND Circulatory disease mortality inequalities by country of birth (COB) have been demonstrated for some EU countries but pan-European analyses are lacking. We examine inequalities in circulatory mortality by geographical region/COB for six EU countries. METHODS We obtained national death and population data from Denmark, England and Wales, France, the Netherlands, Scotland and Sweden. Mortality rate ratios (MRRs) were constructed to examine differences in circulatory, ischaemic heart disease (IHD) and cerebrovascular disease mortality by geographical region/COB in 35-74 years old men and women. RESULTS South Asians in Denmark, England and Wales and France experienced excess circulatory disease mortality (MRRs 1.37-1.91). Similar results were seen for Eastern Europeans in these countries as well as in Sweden (MRRs 1.05-1.51), for those of Middle Eastern origin in Denmark (MRR = 1.49) and France (MRR = 1.15), and for East and West sub-Saharan Africans in England and Wales (MRRs 1.28 and 1.39) and France (MRRs 1.24 and 1.22). Low ratios were observed for East Asians in France, Scotland and Sweden (MRRs 0.64-0.50). Sex-specific analyses showed results of similar direction but different effect sizes. The pattern for IHD mortality was similar to that for circulatory disease mortality. Two- to three-fold excess cerebrovascular disease mortality was found for several foreign-born groups compared with the local-born populations in some countries. CONCLUSIONS Circulatory disease mortality varies by geographical region/COB within six EU countries. Excess mortality was observed for some migrant populations, less for others. Reliable pan-European data are needed for monitoring and understanding mortality inequalities in Europes multiethnic populations.

Prevalence of vitamin B-12 insufficiency during pregnancy and its effect on offspring birth weight: a systematic review and meta-analysis.

BACKGROUND Vitamin B-12 and folate are micronutrients essential for normal embryogenesis. Vitamin B-12 insufficiency in pregnancy is high in certain parts of the world, such as India, and although this has been linked to low birth weight (LBW) in these populations, the relation between vitamin B-12 and birth weight (BW) elsewhere is unknown. OBJECTIVES We performed a systematic review to assess 1) the worldwide prevalence of vitamin B-12 insufficiency in pregnancy and 2) its association with BW. DESIGN A search of 5 electronic databases was performed to identify eligible articles. Random-effects meta-analysis was conducted according to geographic regions and pregnancy trimesters for the prevalence subreview and by categorical measures of BW. RESULTS A total of 57 and 23 articles were included for the prevalence and BW subreviews, respectively. The pooled estimates of vitamin B-12 insufficiency were 21%, 19%, and 29% in the first, second, and third trimesters, respectively, with high rates for the Indian subcontinent and the Eastern Mediterranean. The large heterogeneity between studies was partially addressed by creating a standardized score for each study (mean vitamin B-12 insufficiency ÷ cutoff value), which internally corrected for geographic region, trimester, and assay type. Twelve of the 13 longitudinal studies included showed a decrease in mean or median vitamin B-12 across trimesters. Pooled analysis showed nonsignificantly lower maternal vitamin B-12 concentrations in LBW than in normal-BW infants and higher odds of LBW with lower vitamin B-12 values (adjusted OR: 1.70; 95% CI: 1.16, 2.50), but studies from India largely contributed to the latter. CONCLUSIONS Our review indicates that vitamin B-12 insufficiency during pregnancy is common even in nonvegetarian populations and that concentrations of vitamin B-12 decrease from the first to the third trimester. There is no consistent association between vitamin B-12 insufficiency and LBW. However, given the long-term risks of LBW, this observation warrants further cohort studies and randomized controlled trials.

Longitudinal associations between social connections and subjective wellbeing in the English Longitudinal Study of Ageing

Objective: The role of social relationships in determining well-being may be particularly salient in ageing populations. There is only limited longitudinal research examining the relationship between different dimensions of social relationships and change in well-being over time. The present analysis explores the association between isolation, loneliness and two measures of subjective well-being over six years using data from the English Longitudinal Study of Ageing. Design: Measures of social relationships were obtained at baseline and associations with well-being over the following six years were analysed using mixed models. Main outcome measures: Hedonic and evaluative well-being assessed every two years over the six-year period. Results: Levels of well-being showed a U-shaped relationship with time. At baseline, higher isolation and loneliness were associated with lower levels of hedonic and evaluative well-being. Individuals with high levels of isolation and loneliness initially showed a smaller decrease in evaluative well-being. The subsequent rise in well-being was, however, also diminished in this group. In contrast, loneliness was not associated with rate of change in hedonic well-being, while high levels of isolation were associated with a sustained decrease in hedonic well-being. Conclusion: Social isolation and loneliness show different associations with changes in evaluative and hedonic well-being over time.