Association between anxiety and depression and all-cause mortality: a 50-year follow-up of the Population Study of Women in Gothenburg, Sweden.

OBJECTIVES: This study aimed to examine the association between anxiety disorders and/or major depression disorder (ADs/MDD) and all-cause mortality in a 50-year perspective and to examine specific risk and health factors that may influence such an association. DESIGN: Observational population study, 1968-2019. SETTING: The Population Study of Women in Gothenburg, Sweden (PSWG). PARTICIPANTS: In 1968-1969, 899 (out of 1462) women from PSWG were selected according to date of birth for a psychiatric investigation, including diagnostic evaluation. Eight hundred (89%) were accepted. Twenty-two women were excluded. Of the 778 included, 135 participants (17.4 %) had solely ADs, 32 (4.1%) had solely MDD and 25 (3.2%) had comorbid AD/MDD. PRIMARY AND SECONDARY OUTCOME MEASURES: Associations between ADs, MDD, comorbid AD/MDD and all-cause mortality with adjustments for potential confounding factors. Differences between the groups concerning health and risk factors and their association with mortality. RESULTS: In a fully adjusted model, ADs were non-significantly associated with all-cause mortality (HR 1.17, 95% CI 0.98 to 1.41). When examining age during risk time as separate intervals, a significant association between mortality and AD was seen in the group of participants who died at the age of 65-80 years (HR 1.70, 95% CI 1.26 to 2.29). In the younger or older age interval, the association did not reach significance at the 95% level of confidence. Among confounding factors, smoking and physical activity were the strongest contributors. The association between smoking and mortality tended to be further increased in the group with ADs versus the group without such disorders (HR 2.10, 95% CI 1.60 to 2.75 and HR 1.82, 95% CI 1.56 to 2.12, respectively). CONCLUSIONS: This study suggests potential links between ADs, age and mortality among women with 50 years of follow-up, but does not provide definitive conclusions due to the borderline significance of the results.

Trends in haemoglobin levels from 1968 to 2017 and association with hormonal contraceptives: observations from the population study of women in Gothenburg, Sweden.

AIM: To investigate trends in the haemoglobin (Hb) level in middle-aged Swedish women from 1968 to 2017 and to examine the potential association between Hb and the use of hormonal contraceptives (HCs). DESIGN: A prospective observational population study of representative 38- and 50-year-old women of Gothenburg, Sweden. SETTING: The population study of women in Gothenburg started in 1968-1969 and has continued since then with new examinations every 12 years, including both follow-ups and new recruited cohorts. The study consists of both physical examinations and questionnaires. SUBJECTS: Two thousand four hundred eighty-eight women aged 38 and 50 participated in the study from 1968 to 2017. STATISTICAL METHODS: Linear regression model analyses were used to analyse linear and non-linear trends in the level of Hb. Linear and logistic regression models were used to analyse possible associations between HC and Hb and possible associations between the use of HC and anaemia, respectively. MAIN OUTCOME MEASURES AND COVARIATES: Hb was measured in g/L. HC included any ongoing use of HC therapy. Covariates were smoking, body mass index (BMI), alcohol consumption and education. RESULTS: A non-linear U-shaped trend in mean Hb was seen in the two age groups, 38- and 50-years old. After adjusting for covariates, a significantly higher mean Hb was seen in the 2016-2017 examination compared to 1980-1981, 1992-1993 and 2004-2005. In 38-year-olds, using HC was associated with a reduced risk of anaemia (OR 0.35, 95% CI 0.13-0.75). In both age groups, the use of HC was significantly associated with having a higher Hb. CONCLUSIONS: Mean levels of Hb in middle-aged women of the general population seem to be increasing again after lower levels in the 1980s and 1990s. The use of HC was associated with having a higher Hb and a lower risk of anaemia in 38-year-old women.

Studies of trends in haemoglobin (Hb) in Swedish women are scarce, although many factors associated with Hb levels have changed during the last decades.The use of hormonal contraceptives was associated with higher Hb and decreased risk of anaemia in younger middle-aged women.This study shows there is a non-linear (U-formed) trend in mean Hb, with increasing values since 1992.

Anaemia in patients with self-reported use of iron supplements in the BAriatric surgery SUbstitution and nutrition study: A prospective cohort study.

BACKGROUND AND AIMS: After bariatric surgery, micronutrient deficiencies may lead to anaemia. To prevent post-operative deficiencies, patients are recommended lifelong micronutrient supplementation. Studies investigating the effectiveness of supplementation to prevent anaemia after bariatric surgery are scarce. This study aimed to investigate the relationship between nutritional deficiencies and anaemia in patients who report use of supplementation two years after bariatric surgery versus patients who do not. METHODS AND RESULTS: Obese (BMI≥35 kg/m2) individuals (n = 971) were recruited at Sahlgrenska University Hospital in Gothenburg, Sweden between 2015 and 2017. The interventions were Roux-en-Y gastric bypass (RYGB), n = 382, sleeve gastrectomy (SG), n = 201, or medical treatment (MT), n = 388. Blood samples and self-reported data on supplements were collected at baseline and two years post treatment. Anaemia was defined as haemoglobin <120 g/L for females and <130 g/L for males. Standard statistical methods, including a logistic regression model and a machine learning algorithm, were used to analyse data. The frequency of anaemia increased from baseline in patients treated with RYGB (3·0% vs 10·5%; p < 0·05). Neither iron-dependent biochemistry nor frequency of anaemia differed between participants who reported use of iron supplements and those who did not at the two-year follow-up. Low preoperative level of haemoglobin and high postoperative percent excessive BMI loss increased the predicted probability of anaemia two years after surgery. CONCLUSION: The results from this study indicate that iron deficiency or anaemia may not be prevented by substitutional treatment per current guidelines after bariatric surgery and highlights there is reason to ensure adequate preoperative micronutrient levels. TRIAL REGISTRATION: March 03, 2015; NCT03152617.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Perception of higher frequency of daily hot flashes in 50-year-old women today: a study of trends over time during 48 years in the Population Study of Women in Gothenburg, Sweden.

OBJECTIVE: The aim of this study was to examine if there are any differences in the prevalence of daily hot flashes in 50-year-old women in a longitudinal perspective (from 1968 to 2017). METHODS: Cohort comparisons of four population-based samples of 50-year-old women born in 1918, 1930 (earlier-born cohorts), 1954, and 1966 (later-born cohorts) from the Prospective Population Study of Women in Gothenburg examined in 1968-1969, 1980-1981, 2004-2005, and 2016-2017. Questions about frequency of hot flashes have been formulated in the same way throughout all follow-up examinations. Changes between four generations of 50-year-old women were studied. RESULTS: In the unadjusted model, we found an increased prevalence of daily hot flashes in 50-year-old women born in 1954 and 1966 compared with 50-year-old women born in 1918 and 1930 (odds ratio, 1.74; 95% confidence interval, 1.37-2.22). When considering potential predictors for daily hot flashes (smoking, perceived level of high stress, BMI, waist-to-hip ratio, hormone therapy, and hormonal contraceptives) in the adjusted model, there was a notable difference; odds ratio increases from 1.74 to 1.92 (95% confidence interval, 1.46-2.52). Smoking frequency was substantially lower in the later-born cohorts, 39% compared with 17%. CONCLUSIONS: In this prospective longitudinal study of 50-year-old women, we found nearly twice as high odds of reporting daily hot flashes in the later-born women compared with earlier-born. When controlling for potential predictors, there was still an obvious difference, which cannot be explained in our study. These findings have not earlier been described, and there is a need for further longitudinal population studies investigating the prevalence of hot flashes over time. Moreover, additional research is required exploring the underlying mechanism of hot flashes, as well as studies that take into account potential risk factors in the environment and societal development over time, that is, impacts of endocrine-disrupting chemicals changes in lifestyle, environmental, and dietary factors, as well as working conditions.

Forty-four-year longitudinal study of stroke incidence and risk factors - the Prospective Population Study of Women in Gothenburg.

OBJECTIVE: To assess stroke incidence over 44 years and association with risk factors. To study total stroke incidence at 60-82 years of age and risk factors. DESIGN: Prospective population study. SETTING: Gothenburg, Sweden, with ∼450,000 inhabitants. SUBJECTS: A representative sample of a general population of women (1462 in total) in 5 age strata aged 38-60 years in 1968-1969 (the Population Study of Women in Gothenburg, PSWG) were followed up to the ages of 82-104 years in 2012. Further, analysis was also performed for the age interval 60-82 years. MAIN OUTCOME MEASURES: Incidence of total stroke (TS), ischaemic (IS), haemorrhagic (HS), non-specified (NS) and fatal (FS) strokes and association with baseline classic risk factors (such as hypertension, atrial fibrillation, low physical activity, diabetes, high waist-hip-ratio, hyperlipidaemia, smoking), low education, mental stress, pre-eclampsia and oral health as expressed by loss of teeth and bone score. Blood pressure in levels 1-3 according to modern guidelines. Associations with atrial fibrillation, diabetes and myocardial infarction shown in survival analyses. The five cohorts contributed to risk time data concerning associations with TS in the 60-82 age interval from the examination performed when they were 60. RESULTS: Three hundred and thirty-seven (23%) women had a first-ever stroke, 64 (19%) fatal. TS was associated with physical inactivity, high triglycerides and low education in multivariable analysis. The main sub-type IS was associated with systolic blood pressure, physical inactivity and low education. Pre-eclampsia showed association with IS only in the univariable analysis. FS was associated with systolic blood pressure and smoking. During 60-82 years of age, having <20 teeth (HR 1.74, CI 1.25-2.42), diabetes (HR 2.28 CI 1.09-4.76), WHR (HR 1.29 per 0.1 units CI 1.01-1.63), systolic blood pressure (HR 1.11 per 10 units CI 1.04-1.18) and smoking (HR 1.57, CI 1.14-2.16), were associated with TS in the combined five cohorts. CONCLUSIONS: Several classic risk factors showed independent associations with stroke. Vulnerability factors as low education and oral health, reflected by loss of teeth, also showed association with stroke. All these factors are possible to target in primary care preventive interventions.Key PointsStroke is a common disease and the risk of stroke is a key issue demanding preventive strategies in primary health care. The present prospective population study of women showsOut of 1460 women, almost a quarter got a stroke. The stroke incidence 60-82 years of age was rather stable between the first four age cohorts but somewhat lower in the latest cohort, born 1930.Hypertension, low physical activity, low education and high triglyceride levels but not cholesterol were associated with stroke in women.Low education and loss of teeth are vulnerability factors that should need particular attention.

Associations between alcohol and liver enzymes are modified by coffee, cigarettes, and overweight in a Swedish female population.

PURPOSE: To examine whether positive associations between alcohol and liver enzymes were modified by coffee consumption, smoking, or weight status in a female population. METHODS: Regular consumption of beer, wine, and spirits was assessed in a representative cohort of 1462 Swedish women aged 38-60 in 1968, and re-assessed in 1974. In 1980, gamma-glutamyltransferase (GGT) and aspartase transaminase (AST) were measured in 1130 women. Exposures were averaged over values obtained in 1968 and 1974. Multivariable linear regression linked total ethanol intake to log-transformed enzyme values, including interactions by coffee, smoking, and overweight in mutually adjusted models. RESULTS: Coffee consumption significantly modified the association between ethanol intake and liver enzymes. One g/day higher ethanol intake was associated with 5.5 (3.5, 7.5)% higher values of GGT, and 1.2 (0.4, 2.1)% higher values of AST in women consuming 0-1 cups of coffee per day, while smaller or no effects were observed in women consuming ≥2 cups/day. Synergistic interactions were observed for ethanol and smoking, and for ethanol and overweight. Average alcohol-related effects on GGT in smokers and non-smokers were given by 3.8 (2.7, 4.9)% and 2.1 (0.9, 3.2)% per g ethanol/day, and by 0.9 (0.4, 1.4)% and 0.2 (-0.3, 0.7)% for AST. Similarly, in overweight women, 1 g/day higher ethanol intake was associated with 4.3 (3.0, 5.6)% higher GGT compared to 1.6 (0.7, 2.5)% in non-overweight women. CONCLUSIONS: The results suggest that coffee consumption reduces the enzyme-raising effect of ethanol in the presence of synergistic interactions with smoking and overweight, specifically in women.

Cholesterol and triglyceride levels in midlife and risk of heart failure in women, a longitudinal study: the prospective population study of women in Gothenburg.

OBJECTIVE: To examine the association between triglycerides and cholesterol serum values and risk of developing heart failure in women. DESIGN: Longitudinal observational study of four cohorts 50-year-old women examined in 1968-1969, 1980-1981, 1992-1993 and 2004-2005, and followed until 2012. S-triglycerides and s-cholesterol were measured at baseline and heart failure morbidity and mortality data collected from 1980 to 2012. SETTING: Prospective population study Gothenburg, Sweden. Primary care. PARTICIPANTS: 1143 women 50 year old without history of heart failure or myocardial infarction. MAIN OUTCOME MEASURE: Association among s-triglycerides, s-cholesterol and heart failure expressed as HR for heart failure, adjusted for smoking, body mass index (BMI), physical activity and age. RESULTS: For 50-year-old women examined in 1968-1969, there was an independent association between level of s-triglycerides and heart failure and a significantly higher risk of developing heart failure (HR 1.8; CI 1.16 to 2.80, for each increment of 1.0 mmol/L in s-triglycerides), adjusted for smoking, BMI, physical activity and age. There was no significant association between s-cholesterol and risk of heart failure (HR 0.9; CI 0.77 to 1.15). In the cohorts of 50-year-old women examined in 1980 and 1992, there were no significant associations between neither s-triglycerides or s-cholesterol and the risk of heart failure. In the pooled analyses of the cohorts examined in 1968, 1980 and 1992, a significantly increased risk of heart failure was found (HR 1.49; CI 1.10 to 2.03) for s-triglycerides independently, but not for s-cholesterol. None of the 50-year-old women examined in 2004-2005 developed heart failure by 2012 and were excluded from further analyses. CONCLUSIONS: High levels of s-triglycerides but not s-cholesterol may be a risk marker for later development of heart failure in 50-year-old women.

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Differences in medical services in Nordic general practice: a comparative survey from the QUALICOPC study.

OBJECTIVE: We aim to describe medical services provided by Nordic general practitioners (GPs), and to explore possible differences between the countries. DESIGN AND SETTING: We did a comparative analysis of selected data from the Nordic part of the study Quality and Costs of Primary Care in Europe (QUALICOPC). SUBJECTS: A total of 875 Nordic GPs (198 Norwegian, 80 Icelandic, 97 Swedish, 212 Danish and 288 Finnish) answered identical questionnaires regarding their practices. MAIN OUTCOME MEASURES: The GPs indicated which equipment they used in practice, which procedures that were carried out, and to what extent they were involved in treatment/follow-up of a selection of diagnoses. RESULTS: The Danish GPs performed minor surgical procedures significantly less frequent than GPs in all other countries, although they inserted IUDs significantly more often than GPs in Iceland, Sweden and Finland. Finnish GPs performed a majority of the medical procedures more frequently than GPs in the other countries. The GPs in Iceland reported involvement in a more narrow selection of conditions than the GPs in the other countries. The Finnish GPs had more advanced technical equipment than GPs in all other Nordic countries. CONCLUSIONS: GPs in all Nordic countries are well equipped and offer a wide range of medical services, yet with a substantial variation between countries. There was no clear pattern of GPs in one country doing consistently more procedures, having consistently more equipment and treating a larger diversity of medical conditions than GPs in the other countries. However, structural factors seemed to affect the services offered.

Obesity in Middle Age Increases Risk of Later Heart Failure in Women-Results From the Prospective Population Study of Women and H70 Studies in Gothenburg, Sweden.

OBJECTIVE: Obesity has been shown to be a risk factor for heart failure (HF), but whether the association varies by age is not understood. The aim was to examine the impact of obesity/overweight on the risk of developing heart failure in women of different ages by analysing prospective data from 2 population studies. METHODS: Data were obtained from the Population Study of Women in Gothenburg and the Gerontologic and Geriatric Population Studies concerning body mass index (BMI) collected in 1980 or later. Follow-up ended in 2006. Cox proportional hazard methods were used to determine associations between developing HF and BMI in 2574 women, 1243 aged 26-65 years and 1331 aged 66-76 years, at baseline. RESULTS: Women aged 26-65 years at baseline with BMI ≥30 kg/m2 had an increased risk of developing HF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.56-4.35) even when controlling for age, glucose, smoking, alcohol consumption, serum triglycerides, and systolic blood pressure (reference group: women with BMI 18.5-22.4 kg/m2). Obese women aged 66-76 years at baseline did not show increased risk of developing HF (HR 0.55, 95% CI 0.23-1.29). CONCLUSIONS: Obesity in middle-age women increases their risk of developing HF later in life. In contrast, obesity later in life shows no association with HF.

A primary care lifestyle programme suitable for socioeconomically vulnerable groups - an observational study.

OBJECTIVE: To explore whether a primary health care (PHC) health promotion programme reaches and engages socioeconomically vulnerable groups in a community to the same extent as higher socioeconomic groups. DESIGN: Comparison of level of engagement and lifestyle improvements stratified by socioeconomic vulnerability level. SETTING: Hisingen PHC catchment area (130,000 inhabitants) Gothenburg, Sweden. PARTICIPANTS: Men and women aged 18-79, visiting any of the eight public PHC centres during an eight-month period 2007-2008, were presented with a short intervention health questionnaire and offered a health dialogue with a nurse, including a health profile, p-glucose and blood pressure check. Participants were classified according to four socioeconomic vulnerability factors: education, employment, ethnicity and living situation. RESULTS: Out of 3691 participants, 27% had low education (Hisingen community level 23%), 18% were unemployed (community level 22%), and 16% were born outside Scandinavia (community level 22%). At the one-year follow-up, 2121 (57%) attended. At baseline, 3% of the individuals in the sample had three out of four socioeconomic vulnerability factors, 17% had two vulnerability factors, 43% had one vulnerability factor, and 37% had no vulnerability factors. Improved biological markers were seen in all vulnerability groups (1-3) and odds ratios for improvement were significantly higher in the most socioeconomically vulnerable group for smoking and stress compared to the group with no vulnerability factors. CONCLUSION: Socioeconomically vulnerable groups were reached and lifestyle changes were accomplished to the same extent as in the higher socioeconomic groups in a PHC lifestyle intervention programme. KEY POINTS Primary care plays a major part in prevention of chronic diseases. However, non-pharmacological primary and secondary prevention is often less successful, especially concerning socioeconomically vulnerable groups. The health promoting intervention programme "Pro-Health" reached and engaged socioeconomically vulnerable groups. Participants from the socioeconomically vulnerable groups had comparable odds for lifestyle improvements after one year, compared to participants without vulnerability factors.

Patients' perspectives on the use of the Montgomery-Asberg depression rating scale self-assessment version in primary care.

OBJECTIVE: The aim of the current study was to better understand how patients with depression perceive the use of MADRS-S in primary care consultations with GPs. DESIGN: Qualitative study. Focus group discussion and analysis through Systematic Text Condensation. SETTING: Primary Health Care, Region Västra Götaland, Sweden. SUBJECTS: Nine patients with mild/moderate depression who participated in a RCT evaluating the effects of regular use of the Montgomery-Åsberg Depression Self-assessment scale (MADRS-S) during the GP consultations. MAIN OUTCOME MEASURE: Patients' experiences and perceptions of the use of MADRS-S in primary care. RESULTS: Three categories emerged from the analysis: (I) confirmation; MADRS-S shows that I have depression and how serious it is, (II) centeredness; the most important thing is for the GP to listen to and take me seriously and (III) clarification; MADRS-S helps me understand why I need treatment for depression. CONCLUSION: Use of MADRS-S was perceived as a confirmation for the patients that they had depression and how serious it was. MADRS-S showed the patients something black on white that describes and confirms the diagnosis. The informants emphasized the importance of patient-centeredness; of being listened to and to be taken seriously during the consultation. Use of self-assessment scales such as MADRS-S could find its place, but needs to adjust to the multifaceted environment that primary care provides. Key Points Patients with depression in primary care perceive that the use of a self-assessment scale in the consultation purposefully can contribute in several ways. The scale contributes to Confirmation: MADRS-S shows that I have depression and how serious it is. Centeredness: The most important thing is for the GP to listen to and take me seriously. Clarification: MADRS-S helps me understand why I need treatment for depression.

A 32-year longitudinal study of alcohol consumption in Swedish women: Reduced risk of myocardial infarction but increased risk of cancer.

OBJECTIVE: To assess associations between the intake of different types of alcoholic beverages and the 32-year incidence of myocardial infarction, stroke, diabetes, and cancer, as well as mortality, in a middle-aged female population. DESIGN: Prospective study. SETTING: Gothenburg, Sweden, population about 430 000. SUBJECTS: Representative sample of a general population of women (1462 in total) aged 38 to 60 years in 1968-1969, followed up to the ages of 70 to 92 years in 2000-2001. MAIN OUTCOME MEASURES: Associations between alcohol intake and later risk of mortality and morbidity from myocardial infarction, stroke, diabetes, and cancer, studied longitudinally. RESULTS: During the follow-up period, 185 women developed myocardial infarction, 162 developed stroke, 160 women became diabetic, and 345 developed cancer. Women who drank beer had a 30% lower risk (hazards ratio (HR) 0.70, 95% confidence interval (CI) 0.50-0.95) of developing myocardial infarcion and almost half the risk (HR 0.51 CI 0.33-0.80). A significant association between increased risk of death from cancer and high spirits consumption was also shown (hazards ratio [HR] 1.47, CI 1.06-2.05). CONCLUSIONS: Women with moderate consumption of beer had a reduced risk of developing myocardial infarction. High spirits consumption was associated with increased risk of cancer mortality.

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.

Stroke incidence and association with risk factors in women: a 32-year follow-up of the Prospective Population Study of Women in Gothenburg.

OBJECTIVE: To study stroke incidence among women over 32 years of age with a focus on subdividing by stroke type, to consolidate end points and associations with risk factors. DESIGN: Prospective population study initiated in 1968-1969 with follow-ups in 1974, 1980, 1992 and 2001. SETTING: Gothenburg, Sweden. PARTICIPANTS: A sample of 1462 women from five age strata examined in 1968-1969, representative of women in the general population. MAIN OUTCOME MEASURES: Main types of first-ever stroke and fatal stroke during 1968-2001 identified and validated. Stroke incidence rates in different age strata. Association with baseline smoking, body mass index (BMI), waist-hip ratio, hypertension, serum lipids, physical inactivity, perceived mental stress and education. Associations with atrial fibrillation (AF), diabetes, baseline hypertension and myocardial infarction (MI). Blood pressure (BP) levels 1-3, corresponding to modern guidelines, in relation to stroke risk. RESULTS: 184 (12.6%) cases of first-ever stroke, 33 (18%) of them fatal. Validation reduced unspecified stroke diagnoses from 37% to 11%. Age-standardised incidence rate per 100,000 person-years was 448. A multivariate model showed a significant association between ischaemic stroke and high BMI: HR 1.07 (95% CI 1.02 to 1.12), smoking 1.78 (1.23 to 2.57) and low education 1.17 (1.01 to 1.35). Significant association was seen between haemorrhagic stroke and, besides age, physical inactivity 2.18 (1.04 to 4.58) and for total stroke also hypertension 1.45 (1.02 to 2.08). Survival analysis showed a significantly increased risk of stroke in participants with diabetes (p<0.001), AF (p<0.001) and hypertension (p=0.001), but not MI. Stroke risk increased with increasing BP levels but was already seen for diastolic pressure grade 1 and particularly when combined with systolic BP grade 1; 1.62 (1.17 to 2.25). CONCLUSIONS: Hypertension, smoking, AF, diabetes and high BMI were associated with increased stroke risk. Low education was associated with stroke. Validation of National Patient Registry diagnoses to increase specified diagnoses improved data quality.

Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women.

AIM: To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. METHODS: A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. RESULTS: The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. CONCLUSIONS: Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women.

Perceived mental stress in women associated with psychosomatic symptoms, but not mortality: observations from the Population Study of Women in Gothenburg, Sweden.

PURPOSE: To investigate possible association between mental stress and psychosomatic symptoms, socioeconomic status, lifestyle, as well as incident mortality in a middle-aged female population followed over 37 years. METHODS: A prospective observational study initiated in 1968-1969, including 1462 women aged 60, 54, 50, 46, and 38 years, with follow-ups in 1974-1975, 1980-1981, and 2000-2001, was performed. Measures included self-reported mental stress as well as psychosomatic symptoms and smoking, physical activity, total cholesterol, S-triglycerides, body mass index, waist-hip ratio, blood pressure, socioeconomic status and mortality. RESULTS: Smoking, not being single, and not working outside home were strongly associated with reported mental stress at baseline. Women who reported high mental stress in 1968-1969 were more likely to report presence of abdominal symptoms (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.39-2.46), headache/migraine (OR = 2.04, 95% CI: 1.53-2.72), frequent infections (OR = 1.75, 95% CI: 1.14-2.70), and musculoskeletal symptoms (OR = 1.70, 95% CI: 1.30-2.23) than women who did not report mental stress. Women without these symptoms at baseline 1968-1969, but with perceived mental stress were more likely to subsequently report incident abdominal symptoms (OR = 2.15, 95% CI: 1.39-3.34), headache/migraine (OR = 2.27, 95% CI: 1.48-3.48) and frequent infections (OR = 2.21, 95% CI: 1.12-4.36) in 1974-1975 than women without mental stress in 1968-1969. There was no association between perceived mental stress at baseline and mortality over 37 years of follow-up. CONCLUSION: Women reporting mental stress had a higher frequency of psychosomatic symptoms than women who did not report these symptoms. Not working outside home and smoking rather than low socioeconomic status per se was associated with higher stress levels. Perception of high mental stress was not associated with increased mortality.

Mercury in serum predicts low risk of death and myocardial infarction in Gothenburg women.

PURPOSE: Markers of mercury (Hg) exposure have shown both positive and negative associations with cardiovascular disease (CVD). We assessed the association between serum Hg (S-Hg) and risk of cardiovascular disease in a prospective population-based cohort, with attention to the roles of dental health and fish consumption. METHODS: Total mortality, as well as morbidity and mortality from acute myocardial infarction (AMI) and stroke, was followed up for 32 years in 1,391 women (initially age 38-60), in relation to S-Hg at baseline, using Cox regression models. Potential confounders (age, socioeconomic status, serum lipids, alcohol consumption, dental health, smoking, hypertension, waist-hip ratio, and diabetes) and other covariates (e.g., fish consumption) were also considered. RESULTS: Hazard ratios (HR) adjusted only for age showed strong inverse associations between baseline S-Hg and total mortality [highest quartile: hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.59-0.97], incident AMI (HR 0.56; CI 0.34-0.93), and fatal AMI (HR 0.31; CI 0.15-0.66). Adjustment for potential confounding factors, especially dental health, had a strong impact on the risk estimates, and after adjustment, only the reduced risk of fatal AMI remained statistically significant. CONCLUSIONS: There was a strong inverse association between Hg exposure and CVD. Likely, reasons are confounding with good dental health (also correlated with the number of amalgam fillings in these age groups) and/or fish consumption. The results suggest potential effects of dental health and/or fish consumption on CVD that deserve attention in preventive medicine.

C-reactive protein, fibrinogen, and cardiovascular disease prediction.

BACKGROUND: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS: The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS: In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).