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Prostate cancer (PCa) incidence has steadily increased in Sweden, more steeply in the mid-1990s caused by increased opportunistic prostate-specific antigen (PSA) testing. Tallness, normal weight, and non-smoking are associated with more PSA testing, which increases detection of low-risk and localised PCa. We investigated time trends of height, body mass index (BMI), and smoking with PCa risk in 171,889 men in Sweden aged 50-64 years at baseline, who were linked to nationwide cancer registers during follow-up. Cox regression determined the association of these factors assessed before 1980, 1980-1994, and 1995-2004 with PCa risk. During 15 follow-up years, 8,049 men were diagnosed with PCa. The association of height with PCa was weakly positive across all calendar periods. For obesity (BMI >= 30 kg/m2) vs. normal weight (BMI 18.5-24.9 kg/m2) and current vs. never smoking, the associations changed from null before 1980 (HR 1.03, 95% CI 0.86-1.23, and 1.11, 95% CI 0.97-1.27) to negative in 1995-2004 (HR 0.83, 95% CI 0.74-0.93, and 0.86, 95% CI 0.79-0.93; pinteraction between periods = 0.05 and 0.001). In men with clinical characteristics available, height was positively associated with both aggressive and non-aggressive PCa whilst obesity and smoking showed negative associations only with non-aggressive PCa. These findings likely reflect differences in PSA testing by BMI and smoking habits and contribute important knowledge for etiological studies of PCa.

Background

General adiposity, assessed by body mass index (BMI), is a well-established cancer risk factor. This study compared waist circumference (WC), a measure of abdominal adiposity, with BMI as a risk factor for obesity-related cancers, and assessed whether WC provides additional information beyond BMI.

Methods

We analyzed data from 339 190 individuals in a pooled Swedish cohort with baseline BMI and WC assessments from 1981 to 2019 (61% objectively measured, mean age 51.4 years). Cancer diagnoses were obtained from the Swedish Cancer Register. Hazard ratios (HRs) for WC and BMI were calculated using multivariable-adjusted Cox regression. To account for WC’s greater variability, we corrected HRs using regression dilution ratios. To assess WC’s additional contribution beyond BMI, we analyzed WC residuals in multivariable, BMI-adjusted models.

Results

During a median follow-up of 13.9 years (interquartile range: 8.0-22.5), 18 185 IARC-established obesity-related cancers were recorded. In men, a 1-standard deviation (SD) increase in WC was associated with a 25% higher risk of obesity-related cancers (HR_1-SD = 1.25, 95% CI = 1.21 to 1.30), compared to a 19% increase for BMI (HR_1-SD = 1.19, 95% CI = 1.15 to 1.23, P = 0.014 for heterogeneity). Among women, associations were weaker and similar for both WC (HR_1-SD = 1.13, 95% CI = 1.11 to 1.16) and BMI (HR_1-SD = 1.13, 95% CI = 1.11 to 1.15, P = 0.357 for heterogeneity). Waist circumference residuals were more strongly associated with obesity-related cancer risk in men (HR_1-SD = 1.09, 95% CI = 1.06 to 1.12) than in women (HR_1-SD = 1.03, 95% CI = 1.02 to 1.05). Including an additional 6893 potential obesity-related cancers yielded similar patterns of associations.

Conclusion(s)

Waist circumference is a stronger risk factor than BMI for obesity-related cancer in men, conveying additional risk information, whereas this is less evident in women.

BACKGROUND: The CHA₂DS₂-VASc score predicts poor prognosis in patients with acute myocardial infarction (AMI), with or without atrial fibrillation. In this observational study, we aimed to evaluate the CHA₂DS₂-VASc score by itself and extended with clinical data to predict adverse events in patients after AMI.

METHODS: In this longitudinal observational study, we used a cohort of 955 patients hospitalised for AMI at Västmanland County Hospital, Västerås, Sweden, to derive prediction models. The CHA₂DS₂-VASc score alone and combined with clinical data (systolic blood pressure, creatinine level, ST-segment elevation and diuretic use at discharge) was analysed using Cox regression to evaluate the risk of major adverse events (MAE), defined as all-cause death or hospitalisation due to recurrent MI, heart failure or ischaemic stroke. Discriminatory performance was presented as the time-dependent area under the curve (tdAUC). The prediction models were validated in 416 patients with AMI hospitalised at Uppsala University Hospital, Uppsala, Sweden.

RESULTS: During a median of 2.5 years, 287 (30.1%) patients experienced MAE. CHA₂DS₂-VASc scores of 2, 4 and 6 were associated with fourfold, ninefold and 18-fold increases in the relative risk of MAE, respectively, with a tdAUC of 0.76 at a 2-year follow-up. Extending the CHA₂DS₂-VASc score with clinical data significantly improved the prediction model (p<0.001), yielding a tdAUC of 0.81. The models performed well in the validation cohort, with satisfactory calibration and tdAUC values of 0.70-0.78.

CONCLUSION: The addition of clinical data to the CHA₂DS₂-VASc score was superior to a model with CHA₂DS₂-VASc alone in predicting adverse events in patients after AMI, and the model performed well in external validation.

Purpose: The Obesity and Disease Development Sweden (ODDS) study was designed to create a large cohort to study body mass index (BMI), waist circumference (WC) and changes in weight and WC, in relation to morbidity and mortality.

Participants: ODDS includes 4 295 859 individuals, 2 165 048 men and 2 130 811 women, in Swedish cohorts and national registers with information on weight assessed once (2 555 098 individuals) or more (1 740 761 individuals), in total constituting 7 733 901 weight assessments at the age of 17-103 years in 1963-2020 (recalled weight as of 1911). Information on WC is available in 152 089 men and 212 658 women, out of whom 108 795 have repeated information on WC (in total 512 273 assessments). Information on morbidity and mortality was retrieved from national registers, with follow-up until the end of 2019-2021, varying between the registers.

Findings to date: Among all weight assessments (of which 85% are objectively measured), the median year, age and BMI (IQR) is 1985 (1977-1994) in men and 2001 (1991-2010) in women, age 19 (18-40) years in men and 30 (26-36) years in women and BMI 22.9 (20.9-25.4) kg/m2 in men and 23.2 (21.2-26.1) kg/m2 in women. Normal weight (BMI 18.5-24.9 kg/m2) is present in 67% of assessments in men and 64% in women and obesity (BMI >= 30 kg/m2) in 5% of assessments in men and 10% in women. The median (IQR) follow-up time from the first objectively measured or self-reported current weight assessment until emigration, death or end of follow-up is 31.4 (21.8-40.8) years in men and 19.6 (9.3-29.0) years in women. During follow-up, 283 244 men and 123 457 women died.

Future plans: The large sample size and long follow-up of the ODDS Study will provide robust results on anthropometric measures in relation to risk of common diseases and causes of deaths, and novel findings in subgroups and rarer outcomes.

Background: Growth differentiation factor 15 (GDF-15) is a robust prognostic biomarker in patients with cardiovascular (CV) disease, and a better understanding of its clinical determinants is desirable. We aimed to study the associations between GDF-15 levels and traditional CV risk factors, indicators of atherosclerotic burden, and cardiac geometry and dysfunction in outpatients with peripheral arterial disease (PAD).

Methods: An explorative cross-sectional study (Study of Atherosclerosis in Vastmanland, Västerås, Sweden) included 439 outpatients with carotid or lower extremity PAD. The mean age was 70 years (standard deviation [SD] 7), and 59% of the patients were men. Plasma levels of GDF-15 were obtained along with potential determinants, including medical history, biochemical data, echocardiographic measures of cardiac geometry and function, ankle-brachial index (ABI), and carotid ultrasonographic data on intima-media thickness (IMT) and occurrence of carotid stenosis. The relations between GDF-15 concentrations (transformed with the natural logarithm) and the different determinants were evaluated using uni- and multivariable linear regression models. All pre-specified variables were included in the multivariable models.

Results: The multivariable analysis identified independent relations of GDF-15 with several of the included variables (adjusted R² = 0.48). Diabetes (beta coefficient [β] of 0.37, 95% confidence interval [95% CI] 0.25 to 0.50), low-density lipoprotein (LDL) cholesterol (β = −0.22, 95% confidence interval [CI]: −0.34 to −0.09), and physical activity (β = −0.16, 95% CI: −0.25 to −0.06) had the strongest associations. In contrast, no significant independent associations with GDF-15 level were observed for cardiac geometry and function, ABI, IMT, or carotid stenosis.

Conclusions: Circulating GDF-15 is more strongly associated with traditional CV risk factors, especially diabetes, LDL cholesterol, and physical activity than with specific indicators of atherosclerotic burden or cardiac dysfunction. To better understand the pathophysiological role of GDF-15 and its link to clinical outcomes in patients with PAD, future studies should focus on the metabolic processes involved in atherosclerotic disease.

Objectives: We examined how asymptomatic metabolic syndrome (MetS) in midlife affects cardiovascular (CV) morbidity and all-cause mortality later in life and studied difference in time to event and from the individual components related to MetS.

Design: Population-based matched cohort study including data from a screening programme for identification of CV risk factors.

Setting: Primary care, County of Vastmanland, Sweden.

Participants: All inhabitants turning 40 or 50 years between 1990 and 1999 were invited to a health screening. Total 34 269 (60.1%) individuals completed the health examination. Participants that met a modified definition of MetS were individually matched to two controls without MetS with regard to age, sex and date of health examination.

Interventions: None.

Main outcome measures: CV events and all-cause mortality from the index examination to June 2022.

Results: All 5084 participants with MetS were matched to two controls. There were 1645 (32.4%) CV events in the MetS group and 2321 (22.8%) CV events for controls. 1317 (25.9%) MetS and 1904 (18.7%) control subjects died. The adjusted HRs (aHR) for CV event and death were significantly higher when MetS was present (aHR) 1.39*** (95% CI 1.28 to 1.50) and 1.27*** (95% CI 1.16 to 1.40) respectively. The factor analysis identified three dominating factors: blood pressure, cholesterol and blood glucose. Mean time for first CV event and death was 2.6 years and 1.5 years shorter respectively for participants within the highest quartile compared with participants with lower mean arterial blood pressure (MAP). The aHR for each 10 mm Hg increased MAP were 1.19*** (95% CI 1.15 to 1.23) for CV event and 1.16*** (95% CI 1.11 to 1.21) for death.

Conclusion: The risk of a CV event and premature death is significantly increased when MetS is present. Early detection of metabolic risk factors, especially, high blood pressure, opens a window of opportunity to introduce preventive treatment to reduce CV morbidity and all-cause mortality.

Purpose: We investigated time trends of the obesity-mortality association, accounting for age, sex, and causespecific deaths.

Methods: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17-39 years at baseline in 1963-2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975-1985, ≥1985 and women: <1985, 1985-1994, ≥1995).

Results: Comparing men with obesity vs. normal weight, all-cause and "other-cause" mortality associations decreased over periods; HR (95% CI) 1.92 (1.83-2.01) and 1.70 (1.58-1.82) for all-cause and 1.72 (1.58-1.87) and 1.40 (1.28-1.53) for "other-cause" mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51-2.94) and 3.91 (3.37-4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women.

Conclusions: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

Background: We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays.

Methods: We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs).

Results: For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77.

Conclusion: Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.

Introduction: The metabolic syndrome (MetS) represents a cluster of risk factors that predict cardiovascular disease (CVD) and type 2 diabetes. Early detection of MetS opens up for a successful treatment of the cardiovascular (CV) risk factors involved, hopefully leading to later advent of CVD in the general population.

Purpose: In this long-term, population-based study we aimed to investigate how presence of MetS, in middle-aged men and women, was associated with all-cause mortality and non-fatal CVD later in life.

Methods: Between 1990 -1999 a screening program was conducted among 40- and 50-year-old inhabitants in the County of Västmanland, Sweden. Data on lifestyle habits and socio-economic status were collected. Total cholesterol, fasting blood glucose, blood pressure, weight, height, waist and hip circumference were measured. Individuals that met three or more of the following risk factors were classified with MetS: waist circumference: ≥102 cm (men) and ≥88 cm (women), total cholesterol: ≥6.1 mmol/ l, blood pressure: ≥130 and/ or ≥85 mm Hg (or previous diagnosis of hypertension) or fasting plasma glucose: ≥5.6 mmol/ l (or previous diagnosis of type 2 diabetes). A control group was identified with individuals from the same population, without MetS diagnosis. Each participant with MetS was matched to two controls regarding sex, age and date for the health examination. The association between midlife MetS and all-cause mortality and non-fatal CV events (stroke and myocardial infarction) was adjusted for age, sex, smoking, physical inactivity, educational level, BMI, hip circumference and living alone or with family members. Multivariable cox regression and Kaplan-Meier analyses were used.

Results: A total number of 5084 individuals met the criteria for MetS and a control group of 10 168 individuals was identified. The median (Q1, Q3) follow-up time was 27 years (24.6, 30.1), corresponding to 130 820 and 269 696 person-years at risk in the MetS and the control group respectively. During follow up, 1317 MetS and 1904 control subjects died, implying 10 deaths in the MetS group and 7 deaths in the controls per 1000 person-years at risk (fig. 1). Cox analysis showed increased mortality in the MetS group compared to the controls, hazard ratio (HR) 1.30 (95% CI: 1.20-1.40); p<0.001. Non-fatal CV events in the MetS group and in the controls were 32.4% vs 22.8%, respectively (p<0.001); HR 1.35 (CI;1.25–1.46) (fig 2). Median time (Q1, Q3) for first non-fatal CV event was 16.8 years (9.9,22.3) in the MetS group and 19.1 (12.2, 23.6) for the controls.

Conclusions: Results from this long-term, population-based study underline that the risk of non-fatal CVD and all-cause mortality was significantly higher in individuals with asymptomatic MetS. Present results support previous studies that early identification of MetS with screening programs might open a window of opportunity for prevention of CVD and premature death in the general population.

Background: Patients with peripheral vascular disease (PVD) are often underdiagnosed and undertreated. Nocturnal nondipping blood pressure (BP) pattern, as diagnosed by ambulatory BP monitoring (ABPM), is associated with increased cardiovascular risk, but has not been studied in patients with PVD. We aimed to investigate if a nondipping BP pattern predicts cardiovascular events or all-cause death in outpatients with PVD.

Methods: Consecutive outpatients with carotid or lower-extremity PVD were examined with 24-hour ABPM (n = 396). Nondipping was defined as a < 10% fall in systolic BP level during night-time. We used Cox regression models adjusting for potential confounders. We also evaluated the incremental prognostic value of dipping status in the COPART risk score. Our primary composite outcome was cardiovascular events or all-cause death.

Results: In the cohort (mean age 70; 40% women), 137 events occurred during a 5.1-year median follow-up; incident rate of 7.35 events per 100 person-years. Nondipping was significantly associated with outcome (hazard ratio 1.55, 95% CI 1.07-2.26, p = 0.021) in a fully adjusted model. When adding nondipping to the risk markers in the COPART risk score, the model fit significantly improved (chi(2) 7.91, p < 0.005) and the C-statistic increased from 0.65 to 0.67.

Conclusion: In a cohort of outpatients with PVD, nondipping was an independent risk factor for future cardiovascular events or mortality and seemed to be a strong predictor in patients with carotid artery disease but not in lower-extremity PVD. Additional studies are needed to evaluate the clinical utility of ABPM for improved prevention in these high-risk patients. (ClinicalTrials.gov Identifier: NCT01452165)