Jostein Holmen

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

International Comparison of the Relationship of Chronic Kidney Disease Prevalence and ESRD Risk

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.

Cohort Profile: The HUNT Study, Norway

The HUNT Study includes large total population-based cohorts from the 1980ies, covering 125 000 Norwegian participants; HUNT1 (1984-86), HUNT2 (1995-97) and HUNT3 (2006-08). The study was primarily set up to address arterial hypertension, diabetes, screening of tuberculosis, and quality of life. However, the scope has expanded over time. In the latest survey a state of the art biobank was established, with availability of biomaterial for decades ahead. The three population based surveys now contribute to important knowledge regarding health related lifestyle, prevalence and incidence of somatic and mental illness and disease, health determinants, and associations between disease phenotypes and genotypes. Every citizen of Nord-Trøndelag County in Norway being 20 years or older, have been invited to all the surveys for adults. Participants may be linked in families and followed up longitudinally between the surveys and in several national health- and other registers covering the total population. The HUNT Study includes data from questionnaires, interviews, clinical measurements and biological samples (blood and urine). The questionnaires included questions on socioeconomic conditions, health related behaviours, symptoms, illnesses and diseases. Data from the HUNT Study are available for researchers who satisfy some basic requirements (www.ntnu.edu/hunt), whether affiliated in Norway or abroad.

Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trøndelag Health Study (HUNT), Norway.

BACKGROUND To date, there are few large follow-up studies of apparently healthy subjects with microalbuminuria (MA). The aim of this study is to examine the association between MA and all-cause mortality in nondiabetic nonhypertensive individuals. METHODS We conducted a 4.4-year mortality follow-up of 2,089 men and women (> or =20 years) without diabetes and treated hypertension, randomly selected from the population-based Nord-Trøndelag Health Study (1995 to 1997; n = 65,258). Main outcome measures were adjusted relative risk (RR) for all-cause mortality according to increasing albuminuria, defined at different albumin-creatinine ratio (ACR) levels and in 1/2 or 3 urine samples. The main analysis was performed after exclusion of those with cardiovascular disease. RESULTS There was a positive association between all-cause mortality and MA. The lowest ACR level associated with increased RR for mortality was the 60th percentile (> or =6.7 microg/mg [0.76 mg/mmol]; RR, 2.4; 95% confidence interval, 1.1 to 5.2), applying 3 urine samples with an ACR greater than the cutoff level. We found a positive association between mortality and increasing numbers of urine samples with an ACR greater than different cutoff levels, in which 3 urine samples were superior. Results persisted after adjusting for several confounders and excluding individuals with untreated hypertension (systolic blood pressure > or = 140 mm Hg/diastolic blood pressure > or = 90 mm Hg) and those who died during the first year of follow-up. CONCLUSION Although this study confirms the association of all-cause mortality and ACR level in apparently healthy individuals, intervention trials are necessary before clinical cutoff levels of ACR are established and before screening programs are recommended.

Epidemiology of Stroke in Innherred, Norway, 1994 to 1996 Incidence and 30-Day Case-Fatality Rate

BACKGROUND AND PURPOSE In Norway, as well as other industrialized countries, mortality from stroke has declined over the past decades. Data on stroke morbidity are lacking. This study was conducted to determine the incidence, case fatality, and risk factors of stroke in a defined Norwegian population. METHODS During the period 1994 to 1996, a population-based stroke registry collected uniform information about all cases of first-ever and recurrent stroke occurring in people aged > or = 15 years in the region of Innherred in the central part of Norway (target population 70,000), where the prevalence of cardiovascular risk factors was screened in 1984 to 1986 and 1995 to 1997. RESULTS During the 2 years of registration (September 1, 1994, to August 31, 1996), 432 first-ever (72.8%) and 161 recurrent (27.2%) strokes were registered. The crude annual incidence rate was 3.12/1000 (2.85/1000 for males and 3.38/1000 for females). Adjusted to the European population, the annual incidence rate of first-ever stroke was 2.21/1000. The annual incidence rate of cerebral infarction was 2.32/1000, intracerebral hemorrhage 0.32/1000, subarachnoid hemorrhage 0.19/1000, and unspecified stroke 0.38/1000. The 30-day case-fatality rate was 10.9% for cerebral infarction, 37.8% for intracerebral hemorrhage, and 50.0% for unspecified stroke. Fourteen percent of the patients were found outside the hospital, and only 50% of the suspected stroke cases in the hospital (at admission or reviewed discharge diagnosis of ICD-9 codes 430 to 438) fitted the final inclusion criteria. CONCLUSIONS This first population-based stroke register in Norway revealed incidence rates of stroke similar to other Scandinavian countries, and comparison between other European countries did not indicate regional variations within Western Europe.

Analgesic use: A predictor of chronic pain and medication overuse headache The Head–HUNT Study

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The HUNT study: participation is associated with survival and depends on socioeconomic status, diseases and symptoms

BackgroundPopulation based studies are important for prevalence, incidence and association studies, but their external validity might be threatened by decreasing participation rates. The 50 807 participants in the third survey of the HUNT Study (HUNT3, 2006-08), represented 54% of the invited, necessitating a nonparticipation study.MethodsQuestionnaire data from HUNT3 were compared with data collected from several sources: a short questionnaire to nonparticipants, anonymous data on specific diagnoses and prescribed medication extracted from randomly selected general practices, registry data from Statistics Norway on socioeconomic factors and mortality, and from the Norwegian Prescription Database on drug consumption.ResultsParticipation rates for HUNT3 depended on age, sex and type of symptoms and diseases, but only small changes were found in the overall prevalence estimates when including data from 6922 nonparticipants. Among nonparticipants, the prevalences of cardiovascular diseases, diabetes mellitus and psychiatric disorders were higher both in nonparticipant data and data extracted from general practice, compared to that reported by participants, whilst the opposite pattern was found, at least among persons younger than 80 years, for urine incontinence, musculoskeletal pain and headache. Registry data showed that the nonparticipants had lower socioeconomic status and a higher mortality than participants.ConclusionNonparticipants had lower socioeconomic status, higher mortality and showed higher prevalences of several chronic diseases, whilst opposite patterns were found for common problems like musculoskeletal pain, urine incontinence and headache. The impact on associations should be analyzed for each diagnosis, and data making such analyses possible are provided in the present paper.

Cigarette smoking gives more respiratory symptoms among women than among men The Nord-Trøndelag Health Study (HUNT)

STUDY OBJECTIVE Studies have indicated that women are more vulnerable to the effect of tobacco smoking compared with men. The aim of this study was to explore the prevalence of reported respiratory symptoms and diseases according to smoking burden, age and sex. DESIGN Questionnaire in a cross sectional population based study. SETTING The BONT (Bronchial obstruction in Nord-Trøndelag) study is part of a comprehensive health survey of all inhabitants aged above 19 years in the county of Nord-Trøndelag, Norway, which was carried out from 1995 to 1997. PARTICIPANTS A total of 65 717 subjects, 71.3% of the total population aged 20–100, answered the main questionnaire. MAIN RESULTS In all, 12.7% men and 12.1% women reported episodes of wheezing or breathlessness during the past 12 months, 8.8% men and 8.4% women reported that they had or had had asthma, 7.5% men and 8.2% women had ever used asthma medication, and 4.0% men and 3.0% women reported chronic bronchitis. Thirty per cent of men and 31% of women were smokers, and average pack years of smoking were 15.9 and 10.3, respectively. Among previous and current smokers, significant more women reported episodes of wheezing or breathlessness, current asthma and persistent coughing compared with men with the same smoke burden (pack years) and daily number of cigarettes. CONCLUSION The prevalence of reported asthma and use of asthma medication was higher than reported in previous Scandinavian studies. Respiratory symptoms increased by smoking burden. Comparing the prevalence of symptoms and current asthma among women and men with the same smoke burden or daily cigarette consumption, women seemed to be more susceptible to the effect of tobacco smoking than men.

Cohort Profile: Cohort of Norway (CONOR)

A number of large population-based cardiovascular surveys have been conducted in Norway since the beginning of the 1970s. The surveys were carried out by the National Health Screening Service in cooperation with the universities and local health authorities. All surveys comprised a common set of questions, standardized anthropometric and blood pressure measurements and non-fasting blood samples that were analysed for serum lipids at the Ulleval Hospital Laboratory. These surveys provided considerable experience in conducting large-scale population-based surveys, thus an important background for the Cohort of Norway (CONOR). In the late 1980s the Research Council of Norway established a programme in epidemiology. This also gave stimulus to the idea of establishing a cohort including both core survey data and stored blood samples. In the early 1990s, all universities, the National Health Screening Service, The National Institute of Public Health and the Cancer Registry discussed the possibility of a national representative cohort. The issue of storing blood samples for future analyses raised some concern and it was discussed in the parliament. In 1994, the Ministry of Health appointed the Steering Committee for the CONOR collaboration. In 1994–95, the fourth round of the Tromso Study was conducted, and became the first survey to provide data and blood samples for CONOR. During the years 1994–2003, a number of health surveys that were carried out in other counties and cities also provided similar data for the network. So far, 10 different surveys have provided data and blood samples for CONOR (Figure 1). The administrative responsibility for CONOR was given to the Norwegian Institute of Public Health (NIPH) in 2002. The CONOR collaboration is currently a research collaboration between the NIPH and the Universities of Bergen, Oslo, Tromso and Trondheim.

Change in body mass index and its impact on blood pressure: a prospective population study

BACKGROUND:Overweight and obesity increase the risk of elevated blood pressure, but the knowledge of the effect of weight change on blood pressure is sparse.OBJECTIVE:To investigate the association between change in body mass index (BMI) and change in diastolic blood pressure (DBP), systolic blood pressure (SBP), and hypertension status.DESIGN:Two population-based cross-sectional studies, one in 1984–86 and the other in 1995–97.SETTING:The Nord-Trøndelag Health Study (HUNT).PARTICIPANTS:We included 15 971 women and 13 846 men who were 20 y or older at the first survey, without blood pressure medication at both surveys and without diabetes, cardiovascular disease or dysfunction in daily life at baseline.MEASUREMENTS:Weight, height and blood pressure were measured standardised. Change in BMI was categorised as stable (initial BMI±0.1 kg/m2 each follow-up year), increased or decreased, and BMI was categorised by using World Health Organisations categorisation (underweight BMI: <18.5 kg/m2, normal weight BMI: 18.5–24.9 kg/m2, overweight BMI: 25.0–29.9 kg/m2, obesity BMI≥30 kg/m2).RESULTS:An increase in BMI and a decrease in BMI were significantly associated with increased and decreased SBP and DBP, respectively, compared to a stable BMI in both genders and all age groups, although the strongest effect was found among those who were 50 y and older. The adjusted odds ratio for having hypertension at HUNT 2 was 1.8 (95% confidence interval (CI): 1.5, 2.2) among women and 1.6 (95% CI: 1.4,1.8) among men aged 20–49 y who increased their BMI compared to those who had stable BMI. A similar, but weaker association was found among women and men aged 50 y or more. The mean change in both SBP and DBP was higher for those who changed BMI category from first to the second survey than for those who were in the same BMI class at both surveys.CONCLUSIONS:Our result supports an independent effect of change in BMI on change in SBP and DBP in both women and men, and that people who increase their BMI are at increased risk for hypertension.