Separating the genetics of childhood and adult obesity: a validation study of genetic scores for body mass index in adolescence and adulthood in the HUNT Study.

From a life-course perspective, genetic and environmental factors driving childhood obesity may have a lasting influence on health later in life. However, how obesity trajectories vary throughout the life-course remains unknown. Recently, Richardson et al. created powerful early life and adult gene scores for body mass index (BMI) in a comprehensive attempt to separate childhood and adult obesity. The childhood score was derived using questionnaire-based data administered to adults aged 40-69 regarding their relative body size at age 10, making it prone to recall and misclassification bias. We therefore attempted to validate the childhood and adult scores using measured BMI data in adolescence and adulthood among 66 963 individuals from the HUNT Study in Norway from 1963 to 2019. The predictive performance of the childhood score was better in adolescence and early adulthood, whereas the predictive performance of the adult score was better in adulthood. In the age group 12-15.9 years, the variance explained by the childhood polygenic risk score (PRS) was 6.7% versus 2.4% for the adult PRS. In the age group 24-29.9 years, the variance explained by the adult PRS was 3.9% versus 3.6% for the childhood PRS. Our findings support that genetic factors driving BMI differ at young age and in adulthood. Within the framework of multivariable Mendelian randomization, the validated childhood gene score can now be used to determine the consequence of childhood obesity on later disease.

Use of general practitioner services among youth and young adults in Norway from 2006 to 2021.

OBJECTIVE: To describe the frequency and content of contacts with general practitioners (GPs) among youth and young adults by sex, age and time, emphasizing mental health, sexual health and respiratory tract infections. DESIGN: Registry-based population-wide cohort study. SETTING: General practice in Norway 2006-2021. SUBJECTS: Norwegian residents aged 13-25 within the study period. MAIN OUTCOME MEASURES: Contacts with GPs and out-of-hours services, including type of contact, specific procedures and diagnoses. RESULTS: Average number of GP consultations increased over the study period for all age groups. Conversation therapy and time-consuming consultations increased over time, while chlamydia testing and contraceptive guidance decreased among young women. Consultations with mental health diagnoses increased substantially over the study period for all age groups. Use of GP and out-of-hours services increased with age, with a peak at the end of upper secondary school. Youth more often met their own regular GP when consulting for mental health diagnoses than for respiratory tract infections. CONCLUSION: This study confirmed the continuing trend of increasing use of general practice services among youth, with an increase in conversation therapy and consultations with mental health diagnoses. Procedures related to sexual health became less common. Youth usually meet their regular GP for consultations, in particular those whose diagnosis indicates the highest need of continuity.

Youth are a healthy group with relatively low GP use. However, consultation rates have been increasing in later years.We found that consultation rates increased more over time than can likely be attributed to known policy changes.Consultations with mental diagnoses and conversational therapy increased substantially among youth aged 13­25, while family planning consultations and related procedures decreased.The youth usually meet their own regular GP, particularly if they have diagnoses indicating higher need for follow-up.

Prescription of potentially addictive medications after a multilevel community intervention in general practice.

OBJECTIVE: To evaluate the long-term effects of a multilevel community intervention to improve the quality of prescription practice of potentially addictive medications (PAMs). DESIGN: We conducted a retrospective study, using anonymized data from the Norwegian prescription registry. SETTING: Based on an initiative from the GPs in Molde Municipality in Norway, a multilevel community intervention was initiated by the municipal chief physician in 2018. The intervention targeted GPs, patients, and the public. SUBJECTS: We retrieved prescription data from 26 of 36 GPs. MAIN OUTCOME MEASURES: By using the standardized defined daily dose (DDD), we compared prescription of three groups of PAMs from before the intervention (2017) throughout the intervention in 2018, and through 2020 to determine long-term effects. RESULTS: Three years after the intervention, the GPs in our study sample prescribed 26% less opioids, 38% less benzodiazepines, and 16% less z-hypnotics. Overall prescription of PAMs decreased by 27%. The number of individuals receiving at least 90 DDD of benzodiazepines and z-hypnotics were reduced from 9 to 7 and 34 to 24 per 1000, respectively. Also, the number of individuals receiving two and three PAMs concomitantly were reduced. CONCLUSION: Addressing prescription practice among GPs in a community as a joint intervention, combined with addressing patients and the public may be a feasible method to obtain long-term reduction of PAM prescriptions.Key pointsNon-therapeutic prescriptions of potentially addictive medications (PAMs) are both a public health concern and a frequent challenge in general practice.A multilevel community intervention, targeting general practitioners, patients, and the public, led to 27% reduction in prescription of PAMs.Both the number of daily users and concomitant use of several PAMs were reduced.The reduction in prescription persisted for three years.

Effects of GP characteristics on unplanned hospital admissions and patient safety. A 9-year follow-up of all Norwegian out-of-hours contacts.

BACKGROUND: There are substantial differences in hospital referrals between general practitioners (GPs); however, there is little research on the consequences for patient safety and further healthcare use. OBJECTIVE: To investigate associations between out-of-hours GP characteristics, unplanned hospital admissions, and patient safety. METHODS: This cohort study included all Norwegian out-of-hours services contacts from 2008 to 2016, linked to registry data on patient characteristics, healthcare use and death, and GP age, sex, specialist status, out-of-hours service experience, and prior admission proportion. We estimated the impact from GP characteristics on (i) immediate unplanned hospital admissions for "all conditions," (ii) immediate unplanned hospital admissions for "critical conditions," (iii) 30-day unplanned hospital admissions, (iv) 30-day hospital costs, and (v) 30-day risk of death. To limit confounding, we matched patients in groups by age, time, and location, with an assumption of random assignment of GPs to patients with this design. RESULTS: Patients under the care of older and male GPs had fewer immediate unplanned hospital admissions, but the effects on cumulative 30-day unplanned hospital admissions and costs were small. The GPs' prior admission proportion was strongly associated with both immediate and 30-day unplanned hospital admissions. Higher prior admission proportion was also associated with admitting more patients with critical conditions. There was little evidence of any associations between GP characteristics and 30-day risk of death. CONCLUSIONS: GPs' prior admission proportion was strongly associated with unplanned hospital admissions. We found little effects on 30-day mortality, but more restrictive referral practices may threaten patient safety through missing out on critical cases.

Referral for specialized health services is a key part of the general practitioner (GP) role. Differences in referrals between primary care physicians have been widely studied, as they represent a target for reducing the use of specialized health services. However, the potential consequences beyond the actual referral have received little attention. Studying associations between physician characteristics and clinical decisions are difficult because physicians often systematically see different patient populations with different morbidity. Previous findings showing large differences in clinical decisions regarding referrals and hospital admissions may suffer from confounding. With our carefully matched study design, we could assume that the assignment of physicians to patients was random. We found substantial differences in referrals associated with GP characteristics. Seeing older and male GPs and specialists in family medicine were associated with fewer immediate unplanned hospital admissions but did not substantially influence unplanned hospital costs within 30 days. However, GPs with a history of admitting many of their recent patients had a substantial higher tendency to admit their future patients and represented a higher use of health services and costs. These GPs also referred more critically ill patients, an essential aspect of patient safety. The differences in referrals had minor impact on the patients' 30-day risk of death.

Body mass index and healthcare costs: using genetic variants from the HUNT study as instrumental variables.

BACKGROUND: Past studies have found associations between obesity and healthcare costs, however, these studies have suffered from bias due to omitted variables, reverse causality, and measurement error. METHODS: We used genetic variants related to body mass index (BMI) as instruments for BMI; thereby exploiting the natural randomization of genetic variants that occurs at conception. We used data on measured height and weight, genetic information, and sociodemographic factors from the Nord-Trøndelag Health Studies (HUNT), and individual-level registry data on healthcare costs, educational level, registration status, and biological relatives. We studied associations between BMI and general practitioner (GP)-, specialist-, and total healthcare costs in the Norwegian setting using instrumental variable (IV) regressions, and compared our findings with effect estimates from ordinary least squares (OLS) regressions. The sensitivity of our findings to underlying IV-assumptions was explored using two-sample Mendelian randomization methods, non-linear analyses, sex-, healthcare provider-, and age-specific analyses, within-family analyses, and outlier removal. We also conducted power calculations to assess the likelihood of detecting an effect given our sample 60,786 individuals. RESULTS: We found that increased BMI resulted in significantly higher GP costs; however, the IV-based effect estimate was smaller than the OLS-based estimate. We found no evidence of an association between BMI and specialist or total healthcare costs. CONCLUSIONS: Elevated BMI leads to higher GP costs, and more studies are needed to understand the causal mechanisms between BMI and specialist costs.

Do they cope or mope? A survey of GPs' experiences with the changes in the Norwegian Cervical Cancer Screening Programme.

OBJECTIVE: To explore Norwegian general practitioners' (GPs) experiences with the changes in the cervical cancer screening programme and to uncover which aspects of the programme they find most challenging. DESIGN: We conducted an electronic cross-sectional survey. SETTING: Norwegian GPs were invited to participate in the survey between February and September in 2020. SUBJECTS: One hundred and fifty-five of 429 invited Norwegian GPs responded. MAIN OUTCOME MEASURES: Self-reported measures were used to analyse GPs experiences and beliefs related to the screening programme. RESULTS: Most GPs did not find it particularly challenging to keep up with the changes in the screening programme, regardless of whether they came from areas with HPV-based or cytology-based cervical cancer screening implemented. Challenges concerning the follow-up of patients after an abnormal test were a frequently reported issue. We did not find any differences in how often GPs were uncertain of the follow-up of an abnormal test result in areas with HPV-based compared to cytology-based screening. CONCLUSIONS: The implementation of HPV-based cervical cancer screening in women 34-69 years does not seem to have affected how challenging the GPs perceive the screening programme.Key PointsHow Norwegian general practitioners (GPs) keep up with changes in the Norwegian Cervical Cancer Screening Programme (NCCSP) has not been assessed previously.Most GPs did not find it particularly challenging to keep up with changes in the NCCSP regardless of whether they belonged to an area of HPV-based or cytology-based screening.The follow-up of patients with an abnormal test result was one of the main challenges reported by the GPs.

Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study).

BACKGROUND: Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design. METHODS AND FINDINGS: A total of 67,110 individuals aged 13-80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2). The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data. CONCLUSIONS: In the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic.

Evidence of a causal relationship between body mass index and psoriasis: A mendelian randomization study.

BACKGROUND: Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis. METHODS AND FINDINGS: Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied. CONCLUSIONS: Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.

Temporal changes in health within 5 years before and after disability pension-the HUNT Study.

Background: Health status has been reported to change before, during and after disability pension receipt. These associations might be subject to temporal changes according to changes in policy, incidence of disability pensions and other contextual factors. We compared the perceived health around time of disability retirement among persons receiving disability pension in the 1990 s and 2000 s in Norway. Methods: We linked data from two consecutive cross-sectional population based Norwegian health surveys, HUNT2 (1995-97) and HUNT3 (2006-08), to national registries, identifying those who received disability pension within 5 years before or after participation in the survey (HUNT2: n = 5362, HUNT3: n = 4649). We used logistic regression to assess associations of time from receiving a disability pension with self-rated health, insomnia, depression and anxiety symptoms and subsequently estimated adjusted prevalence over time. Results: Prevalence of poor self-rated health peaked around time of receiving disability pension in both decades. For those aged 50+, prevalence the year before disability pension was slightly lower in 2006-08 (74%, 95% CI 70-79%) than in 1995-97 (83%, 95% CI 79-87%), whereas peak prevalence was similar between surveys for those younger than 50. Depression symptoms peaked more pronouncedly in 1995-97 than in 2006-08, whereas prevalence of anxiety symptoms was similar at time of receiving disability pension between surveys. Conclusions: We found no strong evidence of differences in health selection to disability pension in the 2000 s compared to the 1990 s. However, we found indication of less depression symptoms around time of disability pension in the 2000 s compared to the 1990 s.

The Health Hazards of Marriage. A cohort study of work related disability within 12,500 Norwegian couples - the HUNT Study.

AIMS: Work disability and sickness absence increase following partner's retirement, which similarities in spouses' health could explain. We therefore studied the risk of work disability within couples, taking account of baseline health, lifestyle and socioeconomic factors. METHODS: A cohort of 12,511 couples from the HUNT Study (aged 20-67 years in HUNT2, 1995-1997) was linked to national registries, identifying all new cases of disability pension up until December 2007. Data were analysed with discrete time multilevel logistic regression and Cox regression models. Partners' disability pension was included as a time-varying covariate. Follow-up time was split to examine the association dependent of time. Analyses were adjusted for age only, adjusted for health, and for lifestyle and education along with health. RESULTS: About 15% of an individual's propensity to receive a disability pension could be attributed couple similarity. There was an increased risk of work disability following the spouse's disability retirement [HR (hazard ratio) 1.43 (95% confidence interval 1.20-1.71) for men, HR 1.49 (95% confidence interval 1.28-1.74) for women]. The association was somewhat attenuated after adjustments for health, lifestyle and education. CONCLUSION: There was a substantial clustering of disability pensions within couples, which cannot be explained by similarities in health, lifestyle and education. This suggests partners influence each other's work ability. From a clinical perspective, the family situation needs to be taken into account when addressing health promotion and work participation.

Impact of altering referral threshold from out-of-hours primary care to hospital on patient safety and further health service use: a cohort study.

OBJECTIVES: To estimate the impact of altering referral thresholds from out-of-hours services on older patients' further use of health services and risk of death. DESIGN: Cohort study using patient data from primary and specialised health services and demographic data from Statistics Norway and the Norwegian Cause of Death Registry. SETTING: Norway PARTICIPANTS: 491 653 patients aged 65 years and older contacting Norwegian out-of-hours services between 2008 and 2016. ANALYSIS: Multivariable adjusted and instrumental variable associations between referrals to hospital from out-of-hours services and further health services use and death for up to 6 months.Physicians' proportions of acute referrals of older, unknown patients from out-of-hours work were used as an instrumental variable ('physician referral preference') for their threshold of referral for such patients whose clinical presentations were less clear cut. RESULTS: For older patients, whose referrals could be attributed to their physicians' threshold for referral, mean length of stay in hospital increased 3.30 days (95% CI 3.13 to 3.27) within the first 10 days, compared with non-referred patients. Such referrals also increased 6 months use of outpatient specialist clinics and primary care physicians. Importantly, patients with referrals attributable to their physicians' threshold had a substantially reduced risk of death the first 10 days (HR 0.53, 95% CI 0.31 to 0.91), an effect sustaining through the 6-month follow-up period (HR 0.72, 95% CI 0.54 to 0.97). CONCLUSIONS: Out-of-hours patients whose referrals are affected by physician referral threshold contribute substantially to the use of health services. However, the referral seems protective by reducing the risk of death in the first 6 months after the referral. Thus, raising the threshold for referral to lower pressure on overcrowded emergency departments and hospitals should not be encouraged without ensuring the accuracy of the referral decisions, ideally through high-quality randomised controlled trial evidence.

Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses.

Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.

Quantifying the impact of genes on body mass index during the obesity epidemic: longitudinal findings from the HUNT Study.

OBJECTIVES: To study the trajectories of body mass index (BMI) in Norway over five decades and to assess the differential influence of the obesogenic environment on BMI according to genetic predisposition. DESIGN: Longitudinal study. SETTING: General population of Nord-Trøndelag County, Norway. PARTICIPANTS: 118 959 people aged 13-80 years who participated in a longitudinal population based health study (Nord-Trøndelag Health Study, HUNT), of whom 67 305 were included in analyses of association between genetic predisposition and BMI. MAIN OUTCOME MEASURE: BMI. RESULTS: Obesity increased in Norway starting between the mid-1980s and mid-1990s and, compared with older birth cohorts, those born after 1970 had a substantially higher BMI already in young adulthood. BMI differed substantially between the highest and lowest fifths of genetic susceptibility for all ages at each decade, and the difference increased gradually from the 1960s to the 2000s. For 35 year old men, the most genetically predisposed had 1.20 kg/m2 (95% confidence interval 1.03 to 1.37 kg/m2) higher BMI than those who were least genetically predisposed in the 1960s compared with 2.09 kg/m2 (1.90 to 2.27 kg/m2) in the 2000s. For women of the same age, the corresponding differences in BMI were 1.77 kg/m2 (1.56 to 1.97 kg/m2) and 2.58 kg/m2 (2.36 to 2.80 kg/m2). CONCLUSIONS: This study provides evidence that genetically predisposed people are at greater risk for higher BMI and that genetic predisposition interacts with the obesogenic environment resulting in higher BMI, as observed between the mid-1980s and mid-2000s. Regardless, BMI has increased for both genetically predisposed and non-predisposed people, implying that the environment remains the main contributor.

The effect of smoking intensity on all-cause and cause-specific mortality-a Mendelian randomization analysis.

BACKGROUND: Smoking is an important cause of mortality and recent studies have suggested that even low-intensity smoking might be associated with increased mortality. Still, smoking is associated with lower socio-economic status as well as other potential risk factors, and disease onset might motivate smoking cessation, thus residual confounding and reverse causality might bias results. We aimed to assess the evidence of a causal relationship between smoking intensity and cause-specific as well as all-cause-mortality using Mendelian randomization analyses. METHODS: We included 56 019 participants from the Norwegian HUNT2 Study and 337 103 participants from UK Biobank, linked to national registry data on causes of death. We estimated associations of self-reported smoking as well as the genetic variant rs1051730 as an instrument for smoking intensity with all-cause and cause-specific mortality. We subsequently meta-analysed the results from the two cohorts. RESULTS: Each effect allele of the rs1051730 was associated with a 9% increased hazard of all-cause mortality [95% confidence interval (CI) 6-11] among ever smokers. Effect alleles were also associated with death by neoplasms [hazard ratio (HR) 1.11, 95% CI 1.06-1.15], circulatory diseases (HR 1.06, 95% CI 1.01-1.11) and respiratory diseases (HR 1.15, 95% CI 1.05-1.26) among ever smokers. The association was stronger among ever than never smokers for all-cause mortality (p < 0.001), neoplasms (p = 0.001) and respiratory diseases (p = 0.038). CONCLUSIONS: Our results indicate a causal effect of smoking intensity on all-cause mortality and death by neoplasms and respiratory diseases. There was weaker evidence of a causal effect of smoking intensity on death by circulatory diseases.

Cardiovascular mortality - Comparing risk factor associations within couples and in the total population - The HUNT Study.

BACKGROUND: To compare associations of conventional risk factors with cardiovascular death within couples and in the population as a whole. METHODS: We analysed baseline data (1995-97) from the HUNT2 Study in Norway linked to the national Causes of Death Registry. We compared risk within couples using stratified Cox regression. RESULTS: During 914776 person-years, 3964 cardiovascular deaths occurred, and 1658 of the deaths occurred among 1494 couples. There were consistently stronger associations of serum lipids and blood pressure with cardiovascular mortality within couples compared to the population as a whole. For instance, for systolic blood pressure (per 20mmHg), the hazard ratio (HR) within couples was 1.28 (95% confidence interval: 1.17, 1.40) compared to 1.16 (1.12, 1.20) in the total population, and for diastolic pressure (per 10mmHg), the corresponding HRs were 1.16 (1.07, 1.26) and 1.11 (1.08, 1.13). Anthropometric factors (BMI, waist circumference, waist-hip ratio) as well as diabetes, smoking, physical activity, and education, showed nearly identical positive associations within couples and in the total population. CONCLUSIONS: Prospective population studies may tend to slightly underestimate associations of these factors with cardiovascular mortality.