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1.
Eur J Prev Cardiol ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512434

RESUMO

BACKGROUND: Sex-specific risk predictive performance of N-terminal pro B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase myocardial band (CK-MB), for individual and composite cardiovascular outcomes remains unclear. OBJECTIVES: To evaluate the sex-specific predictive value of NT-proBNP, hs-cTnT and CK-MB for 10-year risk prediction of coronary heart disease (CHD), stroke, heart failure (HF) and composite outcomes. METHODS: 5430 individuals (mean age 68.6 years, 59.9% women) from the Rotterdam Study, with biomarker measurements between 1997-2001, were included. Participants were followed until 2015. We fitted 'basic' models using traditional cardiovascular risk factors. Improvements in c-statistics and net reclassification improvement (NRI) for events and non-events were calculated. RESULTS: During a median follow-up of 14 years, 747 (13.8%), 563 (10.4%), and 664 (12.2%) participants were diagnosed with CHD, stroke, and HF respectively. NT-proBNP improved the discriminative performance of the 'basic' model for all endpoints (c-statistic improvements ranging from 0.007 to 0.050) and provided significant event-net reclassification improvement (NRI) for HF (14.3% in women; 10.7% in men) and for stroke in men (9.3%). The addition of hs-cTnT increased c-statistic for CHD in women by 0.029 (95%CI, 0.011-0.047) and for HF in men by 0.034 (95%CI, 0.014-0.053), and provided significant event-NRI for CHD (10.3%) and HF (7.8%) in women, and for stroke (8.4%) in men. The added predictive value of CK-MB was limited. CONCLUSION: NT-proBNP and hs-cTnT provided added predictive value for various cardiovascular outcomes above traditional risk factors. Sex differences were observed in the predictive performance of these biomarkers.

2.
Eur J Prev Cardiol ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512674

RESUMO

AIMS: To investigate sex-specific longitudinal trajectories of various obesity-related measures and blood pressure at population level and further assess the impact of these trajectories on new-onset atrial fibrillation (AF). METHODS: Participants with ≥2 repeated assessments for various risk factors from the population-based Rotterdam Study were included. Latent class linear mixed models were fitted to identify the potential classes. Cox proportional hazards models were used to assess the association between risk factors' trajectories and risk of new-onset AF, with the most favourable trajectory as reference. RESULTS: Among 7,367 participants (mean baseline age: 73 years, 58.8% women), after a median follow-up time of 8.9 years (interquartile range: 5.3-10.4), 769 (11.4%) participants developed new-onset AF. After adjustments for cardiovascular risk factors, persistent-increasing body mass index (BMI) trajectory carried higher risk for AF [hazard ratio, 95% confidence interval: (1.39; 1.05-1.85) in men, (1.60; 1.19-2.15) in women], compared with the lower-and-stable BMI trajectory. Trajectories of elevated-and-stable waist circumference (WC) in women (1.53; 1.09-2.15) and elevated-and-stable hip circumference (HC) in men (1.83; 1.11-3.03) were associated with incident AF. For systolic blood pressure (SBP), the initially hypertensive trajectory carried the largest risk for AF among women (1.79; 1.21-2.65) and men (1.82; 1.13-2.95). Diastolic blood pressure (DBP) trajectories were significantly associated with AF risk among women, but not men. CONCLUSIONS: Longitudinal trajectories of weight, BMI, WC, HC and SBP were associated with new-onset AF in both men and women. DBP trajectories were additionally associated with AF in women. Our results highlight the importance of assessing long-term exposure to risk factors for AF prevention among men and women.

3.
J Am Heart Assoc ; 11(10): e025303, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579615

RESUMO

Background Consensus lacks concerning a bidirectional association between kidney function and atrial fibrillation (AF), but this is crucial information for prevention/treatment efforts for both chronic kidney disease and AF. Therefore, we investigated the bidirectional association between kidney function and AF. Methods and Results This study was a prospective cohort study including 9228 participants (mean age, 64.9 years; 57.2% women) with information on kidney function (estimated glomerular filtration rate [eGFR] based on serum creatinine [eGFRcreat], cystatin C [eGFRcys], or both [eGFRcreat-cys], and urine albumin-to-creatinine ratio) and AF. Reduced kidney function was defined as eGFRcreat <60 mL/min per 1.73 m2. Cox proportional-hazards, logistic regression, linear mixed, and joint models were used to investigate the association of kidney function with AF and vice versa. During follow-up (median of 8.0 years), 780 events of incident AF occurred. Lower eGFRcys and eGFRcreat-cys were associated with increased AF risk (hazard ratio [HR], 1.08 [95% CI, 1.03-1.14] and HR, 1.07 [95% CI, 1.01-1.14], respectively, per 10 mL/min per 1.73 m2 eGFR decrease). For eGFRcys and eGFRcreat-cys, 10-year cumulative incidence of AF was 16% (eGFR <60) and 6% (eGFR ≥60). Prevalent AF (versus no prevalent AF) was associated with 2.85 mL/min per 1.73 m2 lower eGFRcreat and with a faster decline of eGFRcreat with age. Prevalent AF was associated with a 1.3-fold increased risk of incident reduced kidney function. Conclusions Kidney function, especially eGFRcys, and AF are bidirectionally associated. There are currently no targeted prevention efforts for AF in patients with mild chronic kidney disease and vice versa. Our results could provide the first step to improve prediction/prevention of both conditions.

4.
Heart ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35483871

RESUMO

OBJECTIVE: Longitudinal data on age-related changes in the diameters of the thoracic aorta are scarce. To better understand normal variation and to identify factors influencing this process, we aimed to report male-female-specific and age-specific aortic growth rate in the ageing general population and identify factors associated with growth rate. METHODS: From the prospective population-based Rotterdam Study, 943 participants (52.0% females, median age at baseline 65 years (62-68)) underwent serial non-enhanced cardiac CT. We measured the diameters of the ascending (AA) and descending aorta (DA) at two time points and expressed absolute and relative differences. Linear mixed effects analysis was performed to identify determinants associated with change in aortic diameters. RESULTS: Mean AA diameter at baseline was 37.3±3.6 mm in male population and 34.7±3.2 mm in female population, mean DA diameter was 29.6±2.3 in male population and 26.9±2.2 mm in female population. The median absolute change in diameters during follow-up (mean scan interval 14.1±0.3 years) was 1 mm (0-2) for both the AA and DA. Absolute change per decade in AA diameter was significantly larger in males than in females (0.72 mm/decade (0.00-1.43) vs 0.70 mm/decade (0.00-1.41), p=0.006), as well as absolute change in AD diameter (0.71 mm/decade (0.00-1.42) vs 0.69 mm/decade (0.00-1.36), p=0.008). There was no significant difference between male and female population in relative change of their aortic diameters during follow-up. Age, male sex, higher body mass index (BMI) and higher diastolic blood pressure (DBP) showed a statistically significant independent association with increase in AA and DA diameters over time. CONCLUSIONS: Some degree of increase in thoracic aortic diameters is typical in both men and women of an aging population. Factors associated with this change in thoracic aortic diameters were sex, age, BMI and DBP.

5.
Atherosclerosis ; 348: 44-50, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35452865

RESUMO

BACKGROUND AND AIMS: We aimed to determine associations of plasma amyloid-ß40 (Aß40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. METHODS: Between 2002 and 2005, plasma Aß40 was measured by single molecule array (SiMoA®) in 3879 participants of the population-based Rotterdam Study (mean age: 71 years, 61% female). Subclinical atherosclerosis was quantified as computed tomography-assessed calcification volumes. We determined the association of Aß40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals. RESULTS: Higher levels of Aß40 were associated with increased volumes of calcification in the coronary arteries and to a lesser extent extracranial carotid arteries, independent of traditional cardiovascular risk factors. Of all 3879 participants, 748 developed ASCVD during a median 9.7 years of follow-up. In age- and sex-adjusted models, higher Aß40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02-1.21] per 1-SD increase in Aß40), driven by coronary heart disease (HR: 1.17[1.05-1.29]) rather than stroke (HR: 1.04[0.93-1.16]). However, excess risk of clinical outcomes was largely explained by baseline differences in cardiovascular risk factors and attenuated after further adjustment (for ASCVD- HR: 1.05[0.96-1.15] and for CHD- HR: 1.08[0.96-1.20]). Results were similar in the replication cohort, with highest risk estimates for CHD (HR: 1.24[1.04-1.48]) in age- and sex-adjusted models, attenuated after adjustment for cardiovascular risk factors (HR: 1.15[0.96-1.39]). CONCLUSIONS: In this population-based study, higher plasma amyloid-ß40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Doença das Coronárias , Idoso , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Vasos Coronários , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco
6.
Radiology ; : 210861, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412363

RESUMO

Background Thoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events. Purpose To evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality. Materials and Methods Study participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters. Results A total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes. Conclusion Larger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men. Clinical trial registration no. NTR6831 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Williams in this issue.

7.
Int J Cardiol ; 355: 15-22, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35278573

RESUMO

BACKGROUND: The potential bidirectional causal association between kidney function and atrial fibrillation (AF) remains unclear. METHODS: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis. From multiple genome-wide association studies (GWAS), we retrieved genetic variants associated with kidney function (estimated glomerular filtration rate based on creatinine (eGFRcreat), blood urea nitrogen (BUN), chronic kidney disease (CKD stage ≥G3): n = 1,045,620, eGFR based on cystatin C: n = 24,063-32,861, urine albumin-to-creatinine ratio (UACR), and microalbuminuria: n = 564,257), and AF (n = 1,030,836). The inverse-variance weighted method was used as our main analysis. RESULTS: MR analyses supported a causal effect of CKD (n = 9 SNPs, odds ratio (OR): 1.10, 95% confidence interval (CI): 1.04-1.17, p-value = 1.97 × 10-03), and microalbuminuria (n = 5 SNPs, OR: 1.26, 95% CI: 1.10-1.46, p-value = 1.38 × 10-03) on AF risk. We also observed a causal effect of AF on eGFRcreat (n = 97 SNPs, OR: 1.00, 95% CI: 1.00-1.00, p-value = 6.78 × 10-03), CKD (n = 107 SNPs, OR: 1.06, 95% CI: 1.03-1.09, p-value = 2.97 × 10-04), microalbuminuria (n = 83 SNPs, OR: 1.07, 95% CI: 1.04-1.09, p-value = 2.49 × 10-08), and a suggestive causal effect on eGFRcys (n = 103 SNPs, OR: 0.99, 95% CI: 0.99-1.00, p-value = 4.61 × 10-02). Sensitivity analyses, including weighted median estimator, MR-Egger, the MR pleiotropy residual sum and outlier test, and excluding genetic variants associated with possible confounders and/or horizontal mediators (myocardial infarction/coronary artery disease, heart failure) indicated that these findings were robust. CONCLUSIONS: Our results supported a bidirectional causal association between kidney function and AF. The shared genetic architecture between kidney dysfunction and AF might represent potential important therapeutic targets to prevent both conditions in the general population.


Assuntos
Fibrilação Atrial , Análise da Randomização Mendeliana , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular/genética , Humanos , Rim , Polimorfismo de Nucleotídeo Único/genética
8.
Hum Mol Genet ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234888

RESUMO

Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of Abdominal Aortic Aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in ten cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects (PBIO) as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In GWAS on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, p-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (p-value = 8.19 × 10-4). In exome-array single-variant analysis (p-value threshold = 9 × 10-7), the lowest p-value was found for rs239259 located in SLC22A20 (beta = 0.007, p-value =1.2 × 10-5). In the gene-based analysis (p-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (p-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, p-value = 0.02), triglycerides (beta = -0.16, p-value = 0.008) and height (beta = 0.03, p-value<0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.

9.
Nutrients ; 14(3)2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35276774

RESUMO

Evidence suggests neutral or moderately beneficial effects of dairy intake on type 2 diabetes mellitus risk. Nevertheless, evidence on associations with early phases of type 2 diabetes remains inconsistent. We aimed to examine associations between dairy-type intake with prediabetes risk and longitudinal insulin resistance. The analytic sample consisted of 6770 participants (aged 62 ± 4 years, 59% female) free of (pre-)diabetes at baseline from the prospective population-based Rotterdam Study. Dairy intake was measured at baseline using food frequency questionnaires. Data on prediabetes (fasting blood glucose 6.1-6.9 mmol/L or non-fasting 7.7-11.1 mmol/L) and the longitudinal homeostatic model assessment of insulin resistance (HOMA-IR) were available from 1993-2015. Associations with these outcomes were analyzed with dairy intake in quartiles (Q4 vs. Q1) and continuous using multivariable Cox proportional hazard models and linear mixed models. During a mean follow-up of 11.3 ± 4.8 years, 1139 incident prediabetes cases were documented (18.8%). In models adjusting for sociodemographic, lifestyle and dietary factors, a higher intake of high-fat yogurt was associated with lower prediabetes risk (HRQ4vsQ1 0.70, 95% CI 0.54-0.91 and HRserving/day 0.67, 0.51-0.89). In addition, a higher intake of high-fat milk was associated with lower prediabetes risk (HRQ4vsQ1 0.81, 0.67-0.97, HRserving/day 0.88, 0.79-0.99). Associations were found for low-fat dairy, low-fat milk and total cheese with a higher prediabetes risk (HRserving/day ranging from 1.05-1.07, not significant in quartiles). Associations with longitudinal HOMA-IR were similar to prediabetes for high-fat yogurt, low-fat dairy and low-fat milk. Fermented dairy, low-fat yogurt, high-fat cheese, cream and ice cream were not associated with the outcomes. In conclusion, a higher intake of high-fat yogurt was associated with a lower prediabetes risk and lower longitudinal insulin resistance. Additionally, high-fat milk was associated with a lower prediabetes risk. Some low-fat dairy types were inconsistently associated with these outcomes. Studies are needed to confirm associations and to examine the influence of confounding by population characteristics.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Idoso , Animais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leite , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos
11.
Circ Cardiovasc Imaging ; 15(3): e013602, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35196868

RESUMO

BACKGROUND: Whether information on carotid plaque composition contributes to prediction of incident atherosclerotic cardiovascular disease (ASCVD) remains to be investigated. We determined the sex-specific added value of carotid plaque components for predicting incident ASCVD events, beyond traditional cardiovascular risk factors. METHODS: Between 2007 and 2012, participants from the population-based Rotterdam Study with asymptomatic carotid wall thickening >2.5 mm on ultrasonography were invited for carotid magnetic resonance imaging. Among 1349 participants (mean age: 72 years [SD±9.3], 49.5% women) without cardiovascular disease, we assessed plaque thickness, luminal stenosis (>30%), presence of intraplaque hemorrhage, lipid-rich necrotic core, and calcification. Follow-up for ASCVD was complete until January 1, 2015. Using Cox proportional hazards models, we fitted sex-specific prediction models including traditional cardiovascular risk factors (base model). We extended the base model by single and simultaneous additions of plaque characteristics and calculated improvement of model performance by the C statistics. RESULTS: During a median follow-up of 4.8 years, 60 men and 48 women developed ASCVD. In women, presence of intraplaque hemorrhage was associated with incident ASCVD (adjusted hazard ratio, 3.37 [95% CI, 1.81-6.25]). The C statistic (95% CI) improved from 0.73 (0.66-0.79) to 0.76 (0.70-0.83) after single addition of intraplaque hemorrhage to the base model. Simultaneous addition of plaque components, plaque thickness, and stenosis did not change the results. In men, only carotid stenosis was statistically significantly associated with incident ASCVD (adjusted hazard ratio, 1.75 [95% CI, 1.00-3.08]); yet, the association diminished after the addition of other plaque characteristics, and no improvements were observed in C statistics. CONCLUSIONS: Presence of intraplaque hemorrhage contributes to the prediction of incident ASCVD in women, beyond traditional cardiovascular risk factors, other plaque components, plaque size, and stenosis.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Estenose das Carótidas , Placa Aterosclerótica , Idoso , Aterosclerose/patologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/epidemiologia , Constrição Patológica/complicações , Constrição Patológica/patologia , Feminino , Hemorragia/diagnóstico por imagem , Hemorragia/epidemiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Fatores de Risco
12.
Environ Epidemiol ; 6(1): e184, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35169663

RESUMO

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

13.
BMC Med ; 20(1): 91, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189879

RESUMO

BACKGROUND: HRV has mostly shown associations with systolic dysfunction and more recently, with diastolic dysfunction in Heart failure (HF) patients. But the role of sympathetic nervous system in changes of left ventricular (LV) systolic and diastolic function and new-onset HF has not been extensively studied. METHODS: Among 3157 men and 4405 women free of HF and atrial fibrillation retrospectively included from the population-based Rotterdam Study, we used linear mixed models to examine associations of RR-interval differences and standard deviation of RR-intervals corrected for heart rate (RMSSDc and SDNNc) with longitudinal changes of LV ejection fraction (LVEF), E/A ratio, left atrial (LA) diameter, E/e' ratio. Afterwards, using cox regressions, we examined their association with new-onset HF. RESULTS: Mean (SD) age was 65 (9.95) in men and 65.7 (10.2) in women. Every unit increase in log RMSSDc was accompanied by 0.75% (95%CI:-1.11%;-0.39%) and 0.31% (- 0.60%;-0.01%) lower LVEF among men and women each year, respectively. Higher log RMSSDc was linked to 0.03 (- 0.04;-0.01) and 0.02 (- 0.03;-0.003) lower E/A and also - 1.76 (- 2.77;- 0.75) and - 1.18 (- 1.99;-0.38) lower LVM index in both sexes and 0.72 mm (95% CI: - 1.20;-0.25) smaller LA diameters in women. The associations with LVEF in women diminished after excluding HF cases during the first 3 years of follow-up. During a median follow-up of 8.7 years, hazard ratios (95%CI) for incident HF were 1.34 (1.08;1.65) for log RMSSDc in men and 1.15 (0.93;1.42) in women. SDNNc showed similar associations. CONCLUSIONS: Indices of HRV were associated with worse systolic function in men but mainly with improvement in LA size in women. Higher HRV was associated with higher risk of new-onset HF in men. Our findings highlight potential sex differences in autonomic function underlying cardiac dysfunction and heart failure in the general population.


Assuntos
Insuficiência Cardíaca , Função Ventricular Esquerda , Diástole , Feminino , Insuficiência Cardíaca/epidemiologia , Frequência Cardíaca , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
14.
Eur J Epidemiol ; 37(3): 271-281, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34989970

RESUMO

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women's lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (ß = 0.14, 95% CI = 0.09-0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.

15.
Eur Heart J ; 43(20): 1901-1916, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35089333

RESUMO

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.


Assuntos
Cardiologia , Cardiomiopatias , Cardiomiopatias/genética , Predisposição Genética para Doença/genética , Testes Genéticos , Genômica , Humanos , Fenótipo
16.
Eur J Epidemiol ; 37(2): 205-214, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35083603

RESUMO

Several lifestyle factors have been linked to risk for heart failure (HF) and premature mortality. The aim of this study was to estimate the impact of a healthy lifestyle on life expectancy with and without HF among men and women from a general population. This study was performed among 6113 participants (mean age 65.8 ± 9.7 years; 58.9% women) from the Rotterdam Study, a large prospective population-based cohort study. A continuous lifestyle score was created based on five lifestyle factors: smoking status, alcohol consumption, diet quality, physical activity and weight status (assessed 1995-2008). The lifestyle score was categorized into three levels: unhealthy (reference), intermediate and healthy. Gompertz regression and multistate life tables were used to estimate the effects of lifestyle on life expectancy with and without HF in men and women separately at ages 45, 65 and 85 years (follow-up until 2016). During an average follow-up of 11.3 years, 699 incident HF events and 2146 deaths occurred. At the age of 45 years, men in the healthy lifestyle category had a 4.4 (95% CI: 4.1-4.7) years longer total life expectancy than men in the unhealthy lifestyle category, and a 4.8 (95% CI: 4.4-5.1) years longer life expectancy free of HF. Among women, the difference in total life-expectancy at the age of 45 years was 3.4 (95% CI: 3.2-3.5) years and was 3.4 (95% CI: 3.3-3.6) years longer for life expectancy without HF. This effect persisted also at older ages. An overall healthy lifestyle can have a positive impact on total life expectancy and life expectancy free of HF.


Assuntos
Insuficiência Cardíaca , Expectativa de Vida , Idoso , Estudos de Coortes , Feminino , Estilo de Vida Saudável , Insuficiência Cardíaca/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
Eur J Prev Cardiol ; 28(16): 1850-1857, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583386

RESUMO

AIMS: Data on the lifetime risk of type 2 diabetes (T2D) incidence across different cardiovascular health (CVH) categories are scarce. Moreover, it remains unclear whether a genetic predisposition modifies this association. METHODS AND RESULTS: Using data from the prospective population-based Rotterdam Study, a CVH score (body mass index, blood pressure, total cholesterol, smoking status, diet, and physical activity) was calculated and further categorized at baseline. Genetic predisposition to T2D was assessed and divided into tertiles by creating a genetic risk score (GRS). We estimated the lifetime risk for T2D within different CVH and GRS categories. Among 5993 individuals free of T2D at baseline [mean (standard deviation) age, 69.1 (8.5) years; 58% female], 869 individuals developed T2D during follow-up. At age 55 years, the remaining lifetime risk of T2D was 22.6% (95% CI: 19.4-25.8) for ideal, 28.3% (25.8-30.8) for intermediate, and 32.6% (29.0-36.2) for poor CVH. After further stratification by GRS tertiles, the lifetime risk for T2D was still the lowest for ideal CVH in the lowest GRS tertiles [21.5% (13.7-29.3)], in the second GRS tertile [20.8% (15.9-25.8)], and in the highest tertile [23.5% (18.5-28.6)] when compared with poor and intermediate CVH. CONCLUSION: Our results highlight the importance of favourable CVH in preventing T2D among middle-aged individuals regardless of their genetic predisposition.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Idoso , Pressão Sanguínea/genética , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
18.
Pharmacogenomics J ; 22(1): 55-61, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34616002

RESUMO

Digoxin is characterized by a small therapeutic window and a QT-interval shortening effect. Moreover, it has been shown that the genetic variants of the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. We investigated whether the rs10494366 variant of the NOS1AP gene decreases the QT-interval shortening effect of digoxin in patients using this drug. We included 10,057 individuals from the prospective population-based cohort of the Rotterdam Study during a median of 12.2 (interquartile range (IQR) 6.7-18.1) years of follow-up. At study entry, the mean age was 64 years and almost 59% of participants were women. A total of 23,179 ECGs were longitudinally recorded, of which 334 ECGs were from 249 individuals on digoxin therapy. The linear mixed model analysis was used to estimate the effect of the rs10494366 variant on the association between digoxin use and QT-interval duration, adjusted for age, sex, RR interval, diabetes, heart failure, and history of myocardial infarction. In non-users of digoxin, the GG genotype was associated with a significant 6.5 ms [95% confidence interval (CI) 5.5; 7.5] longer QT-interval duration than the TT variant. In current digoxin users, however, the GG variant was associated with a significantly -23.9 [95%CI -29.5; -18.5] ms shorter mean QT-interval duration than in those with the TT variant with -15.9 [95%CI -18.7; -13.1]. This reduction was strongest in the high digoxin dose category [≥0.250 mg/day] with the GG genotype group, with -40.8 [95%CI -52.5; -29.2] ms changes compared to non-users. Our study suggests that the minor homozygous GG genotype group of the NOS1AP gene rs10494366 variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin in a population of European ancestry.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Cardiotônicos/uso terapêutico , Digoxina/efeitos adversos , Digoxina/uso terapêutico , Síndrome do QT Longo/genética , Idoso , Idoso de 80 Anos ou mais , Digoxina/administração & dosagem , Eletrocardiografia , Feminino , Seguimentos , Variação Genética , Genótipo , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
19.
Clin Res Cardiol ; 111(1): 96-104, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34559294

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF. METHODS: From 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors. RESULTS: We followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93-1.08) for fibrinogen, 1.04 (0.97-1.12) for von Willebrand factor, 1.00 (1.00-1.01) for ADAMTS13, and 1.01 (0.94-1.09) for NETs]. In addition, we found no differences in associations between men and women. CONCLUSION: We found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/imunologia , /imunologia , Idoso , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Imunidade Inata , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Risco , /epidemiologia
20.
Stroke ; 53(4): 1339-1347, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34802249

RESUMO

BACKGROUND: Accumulating evidence highlights the existence of distinct morphological subtypes of intracranial carotid arteriosclerosis. So far, little is known on the prevalence of these subtypes and subsequent stroke risk in the general population. We determined the prevalence of morphological subtypes of intracranial arteriosclerosis and assessed the risk of stroke associated with these subtypes. METHODS: Between 2003 and 2006, 2391 stroke-free participants (mean age 69.6, 51.7% women) from the population-based Rotterdam Study underwent noncontrast computed tomography to visualize calcification in the intracranial carotid arteries as a proxy for intracranial arteriosclerosis. Calcification morphology was evaluated according to a validated grading scale and categorized into intimal, internal elastic lamina (IEL), or mixed subtype. Follow-up for stroke was complete until January 1, 2016. We used multivariable Cox regression to assess associations of each subtype with incident stroke. RESULTS: The prevalence of calcification was 82% of which 39% had the intimal subtype, 48% IEL subtype, and 13% a mixed subtype. During a median follow-up of 10.4 years, 155 participants had a stroke. All 3 subtypes were associated with a higher risk of stroke (adjusted hazard ratio [95% CI] for intimal: 2.11 [1.07-4.13], IEL: 2.66 [1.39-5.11], and mixed subtype 2.57 [1.18-5.61]). The association of the IEL subtype with stroke was strongest among older participants. The association of the intimal subtype with stroke was noticeably stronger in women than in men. CONCLUSIONS: Calcification of the IEL was the most prevalent subtype of intracranial arteriosclerosis. All 3 subtypes were associated with an increased risk of stroke, with noticeable age and sex-specific differences.


Assuntos
Arteriosclerose Intracraniana , Acidente Vascular Cerebral , Artéria Carótida Interna/diagnóstico por imagem , Feminino , Humanos , Arteriosclerose Intracraniana/epidemiologia , Masculino , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Tomografia Computadorizada por Raios X
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