Cecilia Björkelund

A 24-year follow-up of body mass index and cerebral atrophy

Objective: To investigate the longitudinal relationship between body mass index (BMI), a major vascular risk factor, and cerebral atrophy, a marker of neurodegeneration, in a population-based sample of middle-aged women. Methods: A representative sample of 290 women born in 1908, 1914, 1918, and 1922 was examined in 1968 to 1969, 1974 to 1975, 1980 to 1981, and 1992 to 1993 as part of the Population Study of Women in Göteborg, Sweden. At each examination, women completed a survey on a variety of health and lifestyle factors and underwent anthropometric, clinical, and neuropsychiatric assessments and blood collection. Atrophy of the temporal, frontal, occipital, and parietal lobes was measured on CT in 1992 when participants were age 70 to 84. Univariate and multivariate regression analyses were used to assess the relationship between BMI and brain measures. Results: Women with atrophy of the temporal lobe were, on average, 1.1 to 1.5 kg/m2 higher in BMI at all examinations than women without temporal atrophy (p < 0.05). Multivariate analyses showed that age and BMI were the only significant predictors of temporal atrophy. Risk of temporal atrophy increased 13 to 16% per 1.0-kg/m2 increase in BMI (p < 0.05). There were no associations between BMI and atrophy measured at three other brain locations. Conclusion: Overweight and obesity throughout adult life may contribute to the development of temporal atrophy in women.

A century of trends in adult human height

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Associations of serum lipid concentrations and obesity with mortality in women: 20 year follow up of participants in prospective population study in Gothenburg, Sweden.

OBJECTIVE--To examine association of different measures of serum lipid concentration and obesity with mortality in women. DESIGN--Prospective observational study initiated in 1968-9, follow up examination after 12 years, and follow up study based on death certificates after 20 years. SETTING--Gothenburg, Sweden. SUBJECTS--1462 randomly selected women aged 38-60 at start of study. MAIN OUTCOME MEASURES--Total mortality and death from myocardial infarction as predicted by serum cholesterol and triglyceride concentrations, body mass index, and ratio of circumference of waist to circumference of hips. RESULTS--170 women died during follow up, 26 from myocardial infarction. Serum triglyceride concentration and waist:hip ratio were significantly associated with both end points (relative risk of total mortality for highest quarter of triglyceride concentration v lower three quarters 1.86 (95% confidence interval 1.30 to 2.67); relative risk for waist:hip ratio 1.67 (1.18 to 2.36)). These associations remained after adjustment for background variables. Serum cholesterol concentration and body mass index were initially associated with death from myocardial infarction, but association was lost after adjustment for background variables. Serum triglyceride concentration and waist:hip ratio were independently predictive of both end points (logistic regression coefficient for total mortality for triglyceride 0.514 (SE 0.150), p = 0.0006; coefficient for waist:hip ratio 7.130 (1.92), p = 0.0002) whereas the other two risk factors were not (coefficient for total mortality for cholesterol concentration -0.102 (0.079), p = 0.20; coefficient for body mass index -0.051 (0.027), p = 0.05). CONCLUSIONS--Lipid risk profile appears to be different in men and women given that serum triglyceride concentration was an independent risk factor for mortality while serum cholesterol concentration was not. Consistent with previous observations in men, localisation of adipose tissue was more important than obesity per se as risk factor in women.

Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

The Prospective Population Study of Women in Gothenburg, Sweden, 1968-69 to 1992-93 A 24-year follow-up study with special reference to participation, representativeness, and mortality

OBJECTIVE To describe the fourth phase of the Prospective Population Study of Women in Gothenburg, Sweden, with special reference to participation and survival. DESIGN Prospective population study. SETTING City of Gothenburg with about 430,000 inhabitants. PARTICIPANTS 1462 participants and 128 refusers aged 38-60 years at the time of the initial study in 1968-69, 282 women who were sampled but not invited to the study in 1968-69, and 266 women participating since 1980-81 and 32 women for the first time in 1992-93. MAIN OUTCOME MEASURES Participation rate, survival, anthropometric and metabolic characteristics. RESULTS The participation rate throughout the study period was high. The participants were mainly characteristic of women of the same ages in the general population even after 24 years. The mortality after 24 years was higher in non-participants than in participants, while there was no difference in survival between women who were invited and women who were not invited to the study. CONCLUSIONS The initial participants were mainly characteristic of the general population, also after a long follow-up period. The long-term survival was lower in initial refusers than in initial participants.

Asymmetric Dimethylarginine Independently Predicts Fatal and Nonfatal Myocardial Infarction and Stroke in Women 24-Year Follow-Up of the Population Study of Women in Gothenburg

Objective—Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase is associated with cardiovascular disease (CVD). Our study examined the association of ADMA with CVD prospectively in a healthy population-based cohort of women. Methods and Results—We measured baseline ADMA of 880 women in the Population Study of Women in Gothenburg using high-performance liquid chromatography. After adjustment for traditional risk factors, creatinine clearance, and homocysteine using Cox models, the HR (95% CI in parentheses) of CVD end points at 24 years for a 0.15 &mgr;mol/L (1 SD) increase in ADMA were: all-cause mortality 1.12 (0.96, 1.32), fatal CVD 1.30 (1.04, 1.62), total CVD events 1.29 (1.09, 1.53). The top quintile (ADMA ≥0.71 &mgr;mol/L) compared with the bottom four-fifths, conferred a cumulative risk 22 versus 14%, relative risk 1.75 (95% CI 1.18, 2.59) and population attributable risk 12.7% of total CVD events, and further identified individuals who are at higher than expected risk based on the SCORE and Framingham systems. Conclusions—A 0.15 &mgr;mol/L increase in baseline ADMA levels is associated with approximately 30% increase in incident cardiovascular risk at 24 years in women after adjustment. ADMA levels ≥0.71 &mgr;mol/L enhances CVD risk assessment in women.

A longitudinal study of the treatment of hot flushes: the population study of women in Gothenburg during a quarter of a century.

ObjectiveTo describe the prevalence and treatment of hot flushes in premenopausal and postmenopausal women from the 1960s to the 1990s. DesignThis prospective study, based on a random sample of the total female population of 430,000 in Gothenburg, Sweden, was started in 1968, with follow-ups in 1974, 1980, and 1992. The participants were 1,462 women born in 1930, 1922, 1918, 1914, and 1908 (participation rate 90.1%) who were representative of women of the same age in the general population. For the purpose of analyzing secular trends, we included 122 participants who were 38 years old and 47 who were 50 years old in 1980–1981. ResultsThe prevalence of hot flushes increased from ∼11% at 38 years to a maximal prevalence of ∼60% at 52 to 54 years of age, then declined successively from ∼30% at 60 years of age to ∼15% at 66 years of age, and then to ∼9% at 72 years of age. The predominant type of medication being prescribed changed during the observation period from sedatives/anticholinergic drugs in the 1960s to hormone replacement therapy in the 1980s. Hormone replacement therapy was considered to be an effective form of treatment for hot flushes by 70% to 87% of the women. ConclusionsHot flushes were a common symptom, with a maximal prevalence of 64% at 54 years of age. Medical consultation and treatment did not increase in 50-year-old women from 1968–1969 to 1980–1981. Treatment changed and became more effective during the observation period.

Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease

IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

The 32-year relationship between cholesterol and dementia from midlife to late life

Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38–60 years, was initiated in 1968–1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974–1975, 1980–1981, 1992–1993, and 2000–2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimers Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000–2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94–8.43) among those who survived to and participated in the 2000–2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22–4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.