Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?

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.

Nondipping blood pressure pattern predicts cardiovascular events and mortality in patients with atherosclerotic peripheral vascular disease.

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 (χ2 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).

Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes: Meta-Analyses and Mendelian Randomization Analyses.

[Figure: see text].

Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction.

A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (<0.9 or >1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

Do self-reported pregnancy complications add to risk evaluation in older women with established cardiovascular disease?

BACKGROUND: In postmenopausal women with established cardiovascular disease (CVD), it is unknown whether a history of pregnancy complications are related to multisite artery disease (MSAD), defined as atherosclerotic lesions in at least two major vascular beds. Pregnancy complications are an established risk factor for CVD. This study aimed to investigate the frequency of pregnancy complications and their association to specific atherosclerotic manifestations and prediction of MSAD in older women with and without CVD. METHODS: In total, 556 women were invited to participate in the study. Of these women 307 reported former pregnancy from a cohort of women with (n = 233) and without CVD (n = 74). The self-reported frequency of pregnancy complications were surveyed retrospectively by a questionnaire that included miscarriage, subfertility, gestational hypertension (GHT) and/or preeclampsia (PE), low birth weight, preterm birth, bleeding in late pregnancy, gestational diabetes mellitus and high birth weight. Three vascular beds were examined, the peripheral, carotid and coronary arteries. RESULTS: The mean age was 67.5 (SD 9.5) years. GHT and/or PE tended to be more common, but not significant, in women with CVD than in women without (20.3% vs 10.8%, p = 0.066). Among women with GHT and/or PE, hypertension later in life were more frequent than in women without (66.7% vs 47.4%, p = 0.010). GHT and/or PE were not associated with specific atherosclerotic manifestations or prediction of MSAD. CONCLUSIONS: In older women with established CVD, pregnancy complications was not associated to specific atherosclerotic manifestations and may not provide additional value to the risk evaluation for MSAD.

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes.

AIMS/HYPOTHESIS: Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. METHODS: We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. RESULTS: Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. CONCLUSIONS/INTERPRETATION: We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

Socioeconomic characteristics and comorbidities of diverticular disease in Sweden 1997-2012.

PURPOSE: This study aimed to evaluate the association of socioeconomic status and comorbidities with uncomplicated and complicated diverticular disease (DD) in Sweden. METHODS: We identified all individuals aged ≥30 years in Sweden diagnosed with DD between 1997 and 2012 using the Swedish National Population and Housing Census and the Hospital Discharge Register. Data were analyzed by multivariable logistic regression, with individual-level characteristics as covariates. RESULTS: A total of 79,481 patients (median age 66 [range 30-86] years) were hospitalized for DD, 15,878 (20%) of whom for complicated DD. Admissions for both uncomplicated and complicated DD were more common in women (p < 0.001). A low education level was identified as a risk factor for uncomplicated (unadjusted hazard ratio [HR] 1.79, 95% confidence interval [CI] 1.75-1.82; adjusted HR 1.22, 95% CI 1.19-1.24) and complicated DD (unadjusted HR 1.84, 95% CI 1.77-1.92; adjusted HR 1.26, 95% CI 1.21-1.32). Patients with the lowest income had a lower risk of hospitalization for uncomplicated (adjusted HR 0.94, 95% CI 0.91-0.96) and complicated DD (adjusted HR 0.87, 95% CI 0.83-0.92) than those with the highest income. The correlation coefficient between income and education was 0.25. Diabetes and cardiovascular disease were identified as protective factors against uncomplicated DD (adjusted HR 0.68, 95% CI 0.66-0.69 and HR 0.79, 95% CI 0.74-0.84, respectively). CONCLUSIONS: Patients with the lowest education level had an increased risk of hospitalization for DD. Further studies are needed to explore the association of diabetes and cardiovascular disease with uncomplicated DD.

Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy.

BACKGROUND: The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA. METHODS: The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1:1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time ≤5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study. RESULTS: In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99). CONCLUSION: In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

A case-control study of self-reported health, quality-of-life and general functioning among recent immigrants and age- and sex-matched Swedish-born controls.

AIM: To examine whether new immigrants had inferior quality-of-life, well-being and general functioning compared with Swedish age- and sex-matched controls. METHODS: A prospective case-control study was designed including immigrants from non-European countries, 18-65 years of age, with recent Permanent Permits to Stay (PPS) in Sweden, and age- and sex-matched Swedish-born (SB) persons from the general population in Västmanland County, Sweden. The General Health Questionnaire (GHQ-12), the brief version of the World Health Organization Quality-of-Life (WHOQOL-BREF) Scale and the General Activity Functioning Assessment Scale (GAF) from DSM-IV were posted (SB), or applied in personal interviews (PPS) with interpreters. Differences between the PPS and SB groups were measured using McNemar's test and Wilcoxon signed-rank test conducted separately for observations at baseline, 6- and 12-month follow-up. RESULTS: There were 93 pairs (mean age 36 years). Persons from Somalia (67%) and Iraq (27%) dominated the PPS group. The differences between the groups were statistically significant for all time points for the Psychological health and Social relationship domains of WHOQOL-BREF, and for the baseline and 6-month follow-up time points of GHQ-12 where the PPS-group had a higher degree of well-being, health and quality-of-life than the SB. This tendency applied for both sexes in the immigrant group. CONCLUSIONS: These new immigrants did not have inferior physical or psychological health, quality-of-life, well-being or social functioning compared with their age- and sex-matched Swedish born pairs during a 1-year follow-up. Thus, there is reason to advocate immigrants' fast integration into society.

Transcription Factor Activating Protein-2ß (TFAP-2ß) genotype and symptoms of attention deficit hyperactivity disorder in relation to symptoms of depression in two independent samples.

The Transcription Factor Activating Protein-2ß (TFAP-2ß) gene has been shown to influence monoaminergic neurotransmission, and several genes important for monoaminergic function have binding sites for TFAP-2ß. Familial studies of attention deficit hyperactivity disorder (ADHD) suggest a hereditary-determined subtype of ADHD with comorbid depression. We examined a functional variation of the TFAP-2ß gene in the context of co-occurring symptoms of ADHD and depression in two independent population-based samples of adolescents (Group A, n = 175 and Group B, n = 1,506) from Sweden. Results indicated 6.1 to 7.8% of adolescents screened positively for ADHD and depression symptoms. Symptoms of depression were more common among girls who screened positively for ADHD and did not carry the nine-repeat allele of the TFAP-2ß intron 1 Variable Number Tandem Repeat (VNTR) polymorphism. The presence of the nine-repeat variant of the TFAP-2ß intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression.

Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults.

PURPOSE: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific 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.

Cohort profile: The Obesity and Disease Development Sweden (ODDS) study, a pooled cohort.

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.

Type D personality is a risk factor for psychosomatic symptoms and musculoskeletal pain among adolescents: a cross-sectional study of a large population-based cohort of Swedish adolescents.

BACKGROUND: Type D personality, or the "distressed personality", is a psychosocial factor associated with negative health outcomes, although its impact in younger populations is unclear. The purpose of this study was to investigate the prevalence of Type D personality and the associations between Type D personality and psychosomatic symptoms and musculoskeletal pain among adolescences. METHODS: A population-based, self-reported cross-sectional study conducted in Västmanland, Sweden with a cohort of 5012 students in the age between 15-18 years old. The participants completed the anonymous questionnaire Survey of Adolescent Life in Västmanland 2008 during class hour. Psychosomatic symptoms and musculoskeletal pain were measured through index measuring the presence of symptoms and how common they were. DS14 and its two component subscales of negative affectivity (NA) and social inhibition (SI) were measured as well. RESULTS: There was a difference depending on sex, where 10.4% among boys and 14.6% among girls (p = < 0.001) were defined as Type D personality. Boys and girls with a Type D personality had an approximately 2-fold increased odds of musculoskeletal pain and a 5-fold increased odds of psychosomatic symptoms. The subscale NA explained most of the relationship between Type D personality and psychosomatic symptoms and musculoskeletal pain. No interaction effect of NA and SI was found. CONCLUSIONS: There was a strong association between Type D personality and both psychosomatic symptoms and musculoskeletal pain where adolescent with a type D personality reported more symptoms. The present study contributes to the mapping of the influence of Type D on psychosomatic symptoms and musculoskeletal pain among adolescents.

Self-reported family socioeconomic status, the 5-HTTLPR genotype, and delinquent behavior in a community-based adolescent population.

Twin and adoption studies have demonstrated a significant contribution of both genetic and environmental factors to antisocial and delinquent behavior. Associations have been reported between the serotonin transporter (5-HTT) and aggression, and between socioeconomic status (SES), aggression, and serotonergic functions of the brain. We aimed to investigate associations between the 5-HTTLPR genotype and family SES in relation to delinquent behavior among adolescents. A total of 1,467 17- to 18-year-old students in the county of Västmanland, Sweden, anonymously completed a questionnaire and gave a saliva sample. Family SES had a U-shaped relation to delinquency, where adolescents with low and high family SES were the most delinquent. There were curvilinear interactions between the 5-HTTLPR genotype and family SES in relation to delinquency. Among individuals having high family SES, boys with the LL (homozygous for the long allele) or LS (heterozygous) genotypes and girls with the SS (homozygous for the short allele) or LS (heterozygous) genotypes showed the highest delinquency scores. Among individuals having low family SES, boys with the LL (homozygous for the long allele) genotype and girls with the LS (heterozygous) genotype showed the highest delinquency scores. The present study suggests evidence for an interaction between family SES and the 5-HTTLPR genotype in relation to juvenile delinquency.

Intelligence level in late adolescence is inversely associated with BMI change during 22 years of follow-up: results from the WICTORY study.

The objective of this population-based retrospective cohort study was to examine the association between intelligence (IQ) at late adolescence and changes in body mass index (BMI) during 22 years of follow-up until 40 years of age, taking education level into account. Data from 5,286 males born 1950-1959 who had participated in the Westmannia Cardiovascular Risk Factors Study at 40 years of age and attended the Swedish military conscription examination between the ages of 17 and 22 were used. From a mean age of 18 years until follow-up at 40 years of age, BMI increased with a mean (95 % confidence interval (CI)) of 4.36 (4.28-4.43) kg/m(2), equalling 0.20 kg/m(2) per year. The difference in BMI change between IQ levels was strongly statistically significant (P < 0.001), with a strictly inverse relationship between IQ and BMI change. The lowest IQ level (<74) had a mean (95 % CI) BMI increase of 5.19 (4.63-5.74) kg/m(2), equalling 0.24 kg/m(2) per year, compared with 3.73 (3.40-4.07) kg/m(2), equalling 0.17 kg/m(2) per year, for the highest IQ level (>126). Education level also had a strictly inverse relationship with BMI change. After adjusting for confounding variables, including education level, IQ still had a strictly inverse relationship to BMI change, with all IQ levels < 111 having a significantly larger BMI change than IQ > 126 (P < 0.01 for all levels). Education level at 40 years of age but not at 18 years of age had a significant association with BMI change after adjusting for IQ.

Enigma of the cholesterol paradox in acute myocardial infarction: lessons from an 8-year follow-up of all-cause mortality in an age-matched and sex-matched case-control study with controls from the patients' recruitment area.

OBJECTIVE: To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls. DESIGN: Matched case-control study with 8-year follow-up. SETTING: Vastmanland County Hospital, Vasteras, Sweden. PARTICIPANTS: Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population. OUTCOME MEASURES: ACM. RESULTS: Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern. PATIENTS: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality. CONTROLS: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled ≤12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls. CONCLUSIONS: In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox.

Blood pressure screening in midlife aids in prediction of dementia later in life.

BACKGROUND: There is substantial evidence that midlife hypertension is a risk factor for late life dementia. Our aim was to investigate if even high blood pressure at a single timepoint in midlife can predict an increased risk for all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) later in life. METHODS: The community-based study population comprised 30,102 dementia-free individuals from the Westmannia Cardiovascular Risk Factors Study. The participants were aged 40 or 50 years when the health examination took place in 1990-2000. Diagnose registers from both hospitals and primary healthcare centers were used to identify individuals who after inclusion to the study developed dementia. The association between midlife high blood pressure (defined as systolic blood pressure >140 and/or diastolic blood pressure >90 mmHg) at a single timepoint and dementia was adjusted for age, gender, body mass index (BMI), fasting blood glucose, education, smoking, and physical activity level. Multivariate binary cox regression analyses were used. RESULTS: After a mean follow-up time of 24 years resulting in 662,244 person/years, 761 (2.5%) individuals had been diagnosed with dementia. Midlife high blood pressure at a single timepoint predicted all-cause dementia (hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.02-1.45) and VaD (HR: 2.10, 95% CI: 1.47-3.00) but not AD (HR: 1.06, 95% CI: 0.81-1.38). CONCLUSION: This study suggests that even midlife high blood pressure at a single timepoint predicts all-cause dementia and more than doubles the risk for VaD later in life independently of established confounders. Even though there was no such association with AD, this strengthens the importance of midlife health examinations in order to identify individuals with hypertension and initiate treatment.

MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption.

The aim of the present study was to investigate MAOA gene-environment (G*E) interactions in relation to adolescent alcohol consumption. In the county of Västmanland, Sweden, all 17-18-year-old students were asked to complete an anonymous questionnaire and provide a saliva sample during class hours. A total of 2263 students completed the questionnaire (77.4%) and a saliva sample was provided by 2131 participants. Failed MAOA u-variable number of tandem repeats (VNTR) genotype analyses and internal non-responses left 851 boys and 735 girls (total n=1586) to be investigated. Alcohol use disorder identification test was used to measure hazardous alcohol consumption. MAOA u-VNTR was used to measure biological risk in interaction with poor family relations and experience of sexual abuse. The model was also adjusted for non-independent socioeconomic variables, separated parents, type of housing and parental unemployment. Results showed that the MAOA u-VNTR, in interaction with psychosocial risk factors, such as the quality of family relations and sexual abuse, was related to high alcohol consumption among adolescents. Girls, carrying the long MAOA u-VNTR variant showed a higher risk of being high alcohol consumers, whereas among boys, the short allele was related to higher alcohol consumption. The present study supports the hypothesis that there is a relation between MAOA u-VNTR and alcohol consumption and that this relation is modulated by environmental factors. Furthermore, the present study also supports the hypothesis that there is a sex difference in the G*E interaction.

Symptoms of ADHD and depression in a large adolescent population: co-occurring symptoms and associations to experiences of sexual abuse.

BACKGROUND: Symptoms of either attention-deficit hyperactivity disorder (ADHD) or depression constitute the most common reasons for contact with child and adolescent psychiatry. The development of psychiatric symptoms can be explained by a combination of environmental stress events and genetic vulnerability. One common form of environmental stress with high impact on health is sexual abuse. AIMS: To investigate the prevalence and co-occurrence of symptoms of ADHD and depression in relation to experiences of sexual abuse in a large adolescent general population. METHOD: All 15- and 18-year-old students (n = 4910) in the Swedish county of Vestmanland answered a school-based screening instrument including the six-question ADHD self-rating scale (ASRS), the Depression Self-Rating Scale (DSRS) and questions relating to experiences of sexual abuse. RESULTS: The prevalence of co-occurring symptoms of ADHD and depression was 2.4% (boys 1.0%, girls 3.9%). The prevalence of experience of any sexual abuse was 20.9% (boys 13.3%, girls 28.7%). Of those with co-occurring symptoms, 48% of the boys and 47% of the girls reported a history of sexual abuse. CONCLUSIONS: School-based screening for co-occurring symptoms of ADHD and depression might be a method that identifies students at psychiatric and psychosocial risk.

Poorly controlled ambulatory blood pressure in outpatients with peripheral arterial disease.

BACKGROUND: Patients with peripheral arterial disease (PAD) are generally less intensively managed than patients with coronary heart disease (CHD), despite that their risk of complications is believed to be equivalent. Identification of PAD patients at risk of poorly controlled blood pressure (BP) could lead to improved treatment, thus lowering the risk of cardiovascular (CV) complications. We aimed to describe the prevalence of poorly controlled cardiovascular (CV) risk factors, focusing on BP, in outpatients with PAD diagnosed in a vascular ultrasound laboratory. METHODS: Consecutive outpatients with carotid and/or lower extremity PAD were included (n = 402) and examined with blood sampling, clinical BP, and 24-h ambulatory BP measurements. A poorly controlled clinical BP was defined as ≥140/90 mmHg, ambulatory BP ≥130/80 mmHg, low-density lipoprotein (LDL)-cholesterol level ≥2.5 mmol/L, and glycated hemoglobin (HbA1c) level >53 mmol/mol in those with diabetes. RESULTS: Most of the patients had poorly controlled clinical (76.6%) and ambulatory BP (51.7%) profiles. Antihypertensive medications were prescribed in 84% of the patients. However, >40% of them used only 0-1 medication, and <25% of them used three or more agents. Clinical BP, a low number of medications, body mass index, and the presence of diabetes independently predicted a poorly controlled ambulatory BP. Nearly one-third of the patients were smokers, and most of the cohort had an LDL-cholesterol level of ≥2.5 mmol/L. An HbA1c level of >53 mmol/mol was present in 55% of diabetic patients. CONCLUSION: Poorly controlled clinical and ambulatory systolic BP profiles were common. In addition, suboptimal control of other important CV risk factors was detected. The findings of this study highlight the need for better preventive efforts against CV risk factors in outpatients with PAD.