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1.
Atherosclerosis ; 291: 107-113, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31706076

RESUMO

BACKGROUND AND AIMS: COPD is associated with an increased risk of cardiovascular morbidity and mortality, potentially by mechanisms of atherosclerosis. Insight into location-specific vulnerability to atherosclerosis in COPD, including intracranial arteries, is lacking. We aimed to investigate the relation between COPD and atherosclerosis in multiple vessel beds within a large population-based cohort study. METHODS: From 2003 to 2006, a random sample of 2187 elderly participants (mean age, 69.6 ±â€¯6.8 years; 50.9% female; 11.7% COPD) from the population-based Rotterdam Study underwent computed tomography to quantify atherosclerotic coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial carotid artery calcification (ECAC), and intracranial carotid artery calcification (ICAC). We investigated the association of COPD [ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) < 70%] with the presence of calcification and with calcification volumes in each vessel bed using logistic and linear regression, with adjustments for cardiovascular risk factors including smoking. RESULTS: The prevalence of CAC, AAC and ECAC was significantly higher in subjects with COPD compared to those without. After adjusting for age and smoking, COPD remained associated with the presence of ECAC (odds ratio 1.46 [95% confidence interval, 1.02-2.07, p = 0.037]). COPD was significantly associated with larger calcification volumes in all four vessel beds in people in whom calcification was present. CONCLUSIONS: The results of this study suggest that COPD plays a role in extracranial carotid artery atherosclerosis initiation and systemic atherosclerosis aggravation.

2.
PLoS Med ; 16(10): e1002957, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31652264

RESUMO

BACKGROUND: Variations in thyroid function within reference ranges are associated with increased risk of diseases and death. However, the impact of thyroid function on life expectancy (LE) with and without noncommunicable diseases (NCDs) remains unknown. We therefore aimed to investigate the association of thyroid function with total LE and LE with and without NCD among euthyroid individuals. METHODS AND FINDINGS: The study was embedded in the Rotterdam Study, a prospective population-based study carried out in the Netherlands. In total, 7,644 participants without known thyroid disease and with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels within reference ranges were eligible. NCDs were defined as presence of cardiovascular disease, diabetes mellitus type 2, or cancer. We used the demographic tool of multistate life tables to calculate LE estimates at the age of 50 years, using prevalence, incidence rates, and hazard ratios for three transitions (healthy to NCD, healthy to death, and NCD to death). The total LE and LE with and without NCD among TSH and FT4 tertiles were calculated separately in men and women. Analyses were adjusted for sociodemographic and cardiovascular risk factors. The mean (standard deviation) age of the participants was 64.5 (9.7) years, and 52.3% were women. Over a median follow-up of 8 years (interquartile range 2.7-9.9 years), 1,396 incident NCD events and 1,422 deaths occurred. Compared with those in the lowest TSH tertile, men and women in the highest TSH tertile were expected to live 1.5 years (95% confidence interval [CI] 0.8-2.3, p < 0.001) and 1.5 years (CI 0.8-2.2, p < 0.001) longer, respectively, of which 1.4 years (CI 0.5-2.3, p = 0.002) and 1.3 years (CI 0.3-2.1, p = 0.004) with NCD. Compared with those in the lowest FT4 tertile, the difference in LE for men and women in the highest FT4 tertile was -3.7 years (CI -5.1 to -2.2, p < 0.001) and -3.3 years (CI -4.7 to -1.9, p < 0.001), respectively, of which -1.8 years (CI -3.1 to -0.7, p = 0.003) and -2.0 years (CI -3.4 to -0.7, p = 0.003) without NCD. A limitation of the study is the observational design. Thus, the possibility of residual confounding cannot be entirely ruled out. CONCLUSIONS: In this study, we found that people with low-normal thyroid function (i.e., highest tertile of TSH and lowest tertile of FT4 reference ranges) are expected to live more years with and without NCD than those with high-normal thyroid function (i.e., lowest tertile of TSH and highest tertile of FT4 reference ranges). These findings provide support for a re-evaluation of the current reference ranges of thyroid function.

3.
Eur J Prev Cardiol ; : 2047487319877078, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619084

RESUMO

AIMS: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. METHODS AND RESULTS: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. CONCLUSION: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

4.
JCI Insight ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600170

RESUMO

BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (p<5E-8) locus in the KCND3 (potassium voltage gated channel subfamily D member 3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, p=7.7E-12), but did not reveal additional loci. Co-localization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery. CONCLUSIONS: In this study we identified for the first time a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene not only provide insights into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies. FUNDING: For detailed information per study, see Acknowledgments.

5.
Eur Respir J ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601717

RESUMO

Preserved Ratio Impaired Spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80%), PRISm (FEV1/FVC≥0.7, FEV1<80%), and COPD (FEV1/FVC<0.7) at two study visits. Hazard ratios (HR 95%CI) for mortality (until 30/12/2018) were adjusted for age, sex, BMI, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of PRISm subjects with re-examination, 15.7% transitioned to normal spirometry and 49.4% to COPD. Lung function decline (mL·year-1) was highest in subjects with incident PRISm (FEV1: -92.8[-131.9,-65.8]; FVC: -93.3[-159.8,-49.1]), but similar in persistent PRISm (FEV1: -30.2[-67.9,-7.5]; FVC: -20.1[-47.7,+21.7]) and persistent controls (FEV1: -39.6[-64.3,-12.7]; FVC: -20.0[-55.4,+18.8]). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD GOLD2-4 had increased all-cause and cardiovascular mortality (PRISm: HR 1.6[1.2, 2.0] and 2.8[1.5, 5.1]; COPD GOLD2-4: HR 1.7[1.4, 2.1] and 2.1[1.2, 3.6]). Mortality <1 year was highest in PRISm, often having cardiovascular comorbidity (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31638273

RESUMO

OBJECTIVES: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and to estimate 10-year CVD risk and cardiovascular health score. DESIGN: A cross sectional study. PARTICIPANTS: 200 women aged >45 with PCOS, and 200 age-matched controls. MEASUREMENTS: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome, and type-II-diabetes. Ten year Framingham risk score and the cardiovascular health score were calculated, and carotid intima media thickness (cIMT) was measured RESULTS: Mean age was 50.5 years (SD 5.5) in women with PCOS and 51.0 years (SD 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P<0.001). In women with PCOS the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P<0.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. CONCLUSIONS: Middle-aged women with PCOS exhibit only a moderately unfavorable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared to controls from the general population. Long term follow-up of women with PCOS is necessary to provide a definitive answer concerning long term risk for CVD.

7.
Heart ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551294

RESUMO

OBJECTIVE: To provide population-based distributions of thoracic aortic diameters in men and women aged 55 years or older and to identify determinants of thoracic aortic diameters. METHODS: From 2003 to 2006, 2505 participants (1208 men, mean age 69.1±6.8 years) from the prospective population-based Rotterdam Study underwent non-enhanced cardiac CT. The diameter of the ascending (AA) and descending aorta (DA) was measured at the level of the pulmonary bifurcation. RESULTS: The mean diameter of the ascending and descending aorta was substantially larger in men (38±4 mm and 30±2 mm) than in women (35±3 mm and 27±2 mm). An ascending aortic diameter of larger than 40 mm was found in 228 (18.9%) men and 76 (5.9%) women and a descending aortic diameter larger than 40 mm was found in two men and no women. Male sex was found to be independently associated with larger DA diameter (standardised ß 0.24, 95% CI 0.19 to 0.30), while a statistically non-significant trend was found for the AA diameter (standardised ß 0.06, 95% CI 0.00 to 0.12). Age, height, weight and traditional cardiovascular risk factors were also associated with larger AA and/or DA diameters. Diabetes was associated with smaller AA and DA diameters. We found no evidence for effect modification by sex. CONCLUSIONS: In persons aged 55 years or older, an ascending aortic diameter of 40 mm or larger was found in 18.9% of men and 5.9% of women. Given the importance of sex, sex-specific distribution values may prove useful in clinical practice, even when correcting for body surface area or height.

9.
PLoS One ; 14(9): e0222809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536581

RESUMO

OBJECTIVES: Cardiovascular disease (CVD) is one of the major causes of death worldwide. For improved accuracy of CVD prediction, risk classification was performed using national time-series health examination data. The data offers an opportunity to access deep learning (RNN-LSTM), which is widely known as an outstanding algorithm for analyzing time-series datasets. The objective of this study was to show the improved accuracy of deep learning by comparing the performance of a Cox hazard regression and RNN-LSTM based on survival analysis. METHODS AND FINDINGS: We selected 361,239 subjects (age 40 to 79 years) with more than two health examination records from 2002-2006 using the National Health Insurance System-National Health Screening Cohort (NHIS-HEALS). The average number of health screenings (from 2002-2013) used in the analysis was 2.9 ± 1.0. Two CVD prediction models were developed from the NHIS-HEALS data: a Cox hazard regression model and a deep learning model. In an internal validation of the NHIS-HEALS dataset, the Cox regression model showed a highest time-dependent area under the curve (AUC) of 0.79 (95% CI 0.70 to 0.87) for in females and 0.75 (95% CI 0.70 to 0.80) in males at 2 years. The deep learning model showed a highest time-dependent AUC of 0.94 (95% CI 0.91 to 0.97) for in females and 0.96 (95% CI 0.95 to 0.97) in males at 2 years. Layer-wise Relevance Propagation (LRP) revealed that age was the variable that had the greatest effect on CVD, followed by systolic blood pressure (SBP) and diastolic blood pressure (DBP), in that order. CONCLUSION: The performance of the deep learning model for predicting CVD occurrences was better than that of the Cox regression model. In addition, it was confirmed that the known risk factors shown to be important by previous clinical studies were extracted from the study results using LRP.

10.
J Am Med Dir Assoc ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31399361

RESUMO

OBJECTIVES: Cardiovascular disease may be linked to hearing loss through narrowing of the nutrient arteries of the cochlea, but large-scale population-based evidence for this association remains scarce. We investigated the association of carotid atherosclerosis as a marker of generalized cardiovascular disease with hearing loss in a population-based cohort. DESIGN: Cross-sectional. SETTING: A population-based cohort study. PARTICIPANTS: 3724 participants [mean age: 65.5 years, standard deviation (SD): 7.5, 55.4% female]. METHODS: Ultrasound and pure-tone audiograms to assess carotid atherosclerosis and hearing loss. RESULTS: We investigated associations of carotid plaque burden and carotid intima-media thickness (IMT) (overall and side-specific carotid atherosclerosis) with hearing loss (in the best hearing ear and side-specific hearing loss) using multivariable linear and ordinal regression models. We found that higher maximum IMT was related to poorer hearing in the best hearing ear [difference in decibel hearing level per 1-mm increase in IMT: 2.09 dB, 95% confidence interval (CI): 0.08, 4.10]. Additionally, third and fourth quartile plaque burden as compared to first quartile was related to poorer hearing in the best hearing ear (difference: 1.06 dB, 95% CI: 0.04, 2.08; and difference: 1.55 dB, 95% CI: 0.49, 2.60, respectively). Larger IMT (difference: 2.97 dB, 95% CI: 0.79, 5.14), third quartile plaque burden compared to first quartile (difference: 1.24 dB, 95% CI: 0.14, 2.35), and fourth plaque quartile compared to first quartile (difference: 2.12 dB, 95% CI: 0.98, 3.26) in the right carotid were associated with poorer hearing in the right ear. CONCLUSIONS AND IMPLICATIONS: Carotid atherosclerosis is associated with poorer hearing in older adults, almost exclusively with poorer hearing in the right ear. Based on our results, it seems that current therapies for the prevention of cardiovascular disease may also prove beneficial for hearing loss in older adults by promoting and maintaining inner ear health.

11.
Korean Circ J ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31456363

RESUMO

BACKGROUND AND OBJECTIVES: We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression. METHODS: Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included. RESULTS: Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886-0.907) in men and 0.921 (0.908-0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860-0.876) in men and 0.889 (0.876-0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824-0.897) in men and 0.867 (0.830-0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women). CONCLUSIONS: A DL algorithm exhibited greater discriminative accuracy than Cox model approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02931500.

12.
Sci Rep ; 9(1): 9439, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263163

RESUMO

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10-8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.

13.
J Hypertens ; 37(8): 1729-1730, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31246771
14.
Diabetologia ; 62(9): 1581-1590, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183505

RESUMO

AIMS/HYPOTHESIS: Both visceral and truncal fat have been associated with metabolic disturbances. We aimed to investigate the associations of several novel metabolic indices, combining anthropometric and lipid measures, and dual-energy x-ray absorptiometry (DXA) measurements of body fat, with incident type 2 diabetes among women and men from the large population-based Rotterdam Study. METHODS: Cox proportional hazards models were used to investigate associations of visceral adiposity index (VAI), lipid accumulation product (LAP), the product of triacylglycerol and glucose (TyG), their formula components and DXA measures with incident type 2 diabetes. Associations were adjusted for traditional diabetes risk factors. RESULTS: Among 5576 women and 3988 men free of diabetes, 511 women and 388 men developed type 2 diabetes during a median follow-up of 6.5 years. In adjusted models, the three metabolic indices VAI (per 1 SD naturally log-transformed HR; 95% CI) (1.49; 1.36, 1.65 in women; 1.37; 1.22, 1.53 in men), LAP (1.35; 1.16, 1.56 in women; 1.19; 1.01, 1.42 in men) and TyG (1.73; 1.52, 1.98 in women; 1.43; 1.26, 1.62 in men), gynoid fat mass (0.63; 0.45, 0.89) and android to gynoid fat ratio (1.51; 1.16, 1.97) in women were associated with incident type 2 diabetes. BMI (1.45; 1.28, 1.65) was the strongest predictor of type 2 diabetes in men. CONCLUSIONS/INTERPRETATION: Among women, novel combined metabolic indices were stronger risk markers for type 2 diabetes than the traditional anthropometric and laboratory measures and were comparable with DXA measures. Neither combined metabolic indices nor DXA measures were superior to traditional anthropometric and lipid measures in association with type 2 diabetes among men.

16.
Atherosclerosis ; 286: 46-52, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100619

RESUMO

BACKGROUND AND AIMS: Arteriosclerosis in the vertebrobasilar arteries may play an important role in the etiology of posterior circulation strokes, but little is known on its prevalence, its correlation with arteriosclerosis in other major arteries, and its risk factors. Hence, we investigated these aspects of vertebrobasilar artery calcification (VBAC) as marker of vertebrobasilar arteriosclerosis. METHODS: To quantify VBAC, 2483 participants (mean age: 69.2 years, 52% female) from the Rotterdam Study underwent non-enhanced computed tomography. We determined the presence and volume of VBAC. Next, using Spearman's rank correlation, we examined the correlation between the volume of VBAC and the volume of coronary artery calcification (CAC), aortic arch calcification (AAC), and both extracranial- (ECAC), and intracranial carotid artery calcification (ICAC). Finally, we investigated associations of cardiovascular risk factors with the presence and volume of VBAC using logistic and linear regression models. RESULTS: The overall prevalence of VBAC was 21.0% (median volume: 7.3 mm3 [IQR: 2.0-25.6]). Correlations between VBAC and CAC, AAC, ECAC, and ICAC were weak to moderate (men: 0.33, 0.28, 0.30, 0.36; women: 0.26, 0.24, 0.24, 0.35, respectively). Hypertension, diabetes, and current smoking were associated with the presence of VBAC in both sexes (men: OR 1.67 [95%-CI, 1.14-2.46], 1.60 [95%-CI, 1.10-2.34], 1.48 [95%-CI, 1.02-2.14]; women: OR 1.51 [95%-CI, 1.01-2.26], 1.56 [95%-CI, 1.02-2.39], 1.53 [95%CI, 1.00-2.33], respectively). In men, obesity was also associated with VBAC (1.42 [95%-CI, 1.00-2.02]). CONCLUSIONS: VBAC occurs in over 20% of elderly community dwelling persons. Cardiovascular risk factors are associated with VBAC with similar patterns for men and women.

17.
Eur Heart J ; 40(34): 2883-2896, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31102408

RESUMO

AIMS: To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). METHODS AND RESULTS: We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05). CONCLUSION: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis.

18.
Cephalalgia ; 39(8): 1041-1048, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30961370

RESUMO

BACKGROUND: To explore the role of large-artery atherosclerosis in migraine, we investigated the association between migraine and arterial calcification in different intracranial and extracranial vessels. METHODS: 1856 participants were included, mean age (standard deviation) 67.4 (5.8) years, from the population-based Rotterdam Study cohort. Migraine was assessed by validated questionnaire and vascular calcification was assessed by computed tomography (expressed in Agatston score for the coronary arteries and volume in mm3 for the aortic arch, intracranial, and extracranial carotid arteries). Per vessel, the association of migraine with calcification was investigated by linear regression, adjusted for age, sex, cardiovascular risk factors, and calcification in other vessels. RESULTS: Of the participants, 279 (15%) were identified as persons with lifetime migraine. In multivariable adjusted models, migraine was associated with smaller intracranial carotid artery calcification volume (difference in log-transformed calcification volume in persons with migraine compared to persons without migraine: -0.19[-0.29, -0.08]). While subjects with migraine also showed a lower calcification burden in the remaining arterial beds, those associations did not reach statistical significance. CONCLUSIONS: Persons with migraine, compared to those without, had less arterial calcification in the intracranial carotid artery, but not in other arterial beds. Future studies are needed to confirm these findings.

19.
Heart ; 105(18): 1414-1422, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30936410

RESUMO

OBJECTIVE: To evaluate changes in left ventricular diastolic function (LVDF) parameters and their associated risk factors over a period of 11 years among community-dwelling women and men. METHODS: Echocardiography was performed three times among 870 women and 630 men (age 67±3 years) from the prospective population-based Rotterdam Study during a period of 11-year follow-up. Changes in six continuous LVDF parameters were correlated with cardiovascular risk factors using a linear-mixed effect model (LMM). RESULTS: In women, smoking was associated with deleterious longitudinal changes in deceleration time (DT) (Beta (ß): 7.73; 95% CI 2.56 to 12.9) and high-density lipoprotein cholesterol was associated with improvement of septal e' (ß: 0.37; 95% CI 0.13 to 0.62) and E/e' ratio (ß: -0.46; 95% CI -0.84 to -0.08) trajectories. Among men, diabetes was associated with deleterious longitudinal changes in A wave (ß: 3.83; 95% CI 0.06 to 7.60), septal e' (ß: -0.40; 95% CI -0.70 to -0.09) and E/e' ratio (ß: 0.60; 95% CI 0.14 to 1.06) and body mass index was associated with deleterious longitudinal changes in A wave (ß: 1.25; 95% CI 0.84 to 1.66), E/A ratio (ß: -0.007; 95% CI -0.01 to -0.003), DT (ß: 0.86; 95% CI 0.017 to 1.71) and E/e' ratio (ß: 0.12; 95% CI 0.06 to 0.19). CONCLUSIONS: Smoking among women and metabolic factors (diabetes mellitus and body mass index) among men showed larger deleterious associations with longitudinal changes in LVDF parameters. The favourable association of HDL was mainly observed among women. This study, for the first time, evaluates risk factors associated with changes over time in continuous LVDF parameters among women and men and generates new hypothesis for further medical research.

20.
J Clin Endocrinol Metab ; 104(8): 3203-3212, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30938758

RESUMO

CONTEXT: Mechanisms linking high and high-normal thyroid function to increased cardiovascular risk remain unclear. Hypothetically, coagulation can play a role. OBJECTIVE: To investigate (i) the association of thyroid function with coagulation factors and (ii) whether coagulation factors mediate the association of thyroid function with cardiovascular disease (CVD). DESIGN AND SETTING: Rotterdam Study, a population-based prospective study. PARTICIPANTS AND MAIN OUTCOME MEASURES: In 5918 participants (mean age, 69.1 years), we measured TSH, free T4 (FT4), and coagulation factors [von Willebrand factor antigen (VWF:Ag), ADAMTS13 activity, fibrinogen]. Participants were followed up for the occurrence of cardiovascular events and deaths. Associations of thyroid function with coagulation factors (standardized z scores) and CVD were assessed through linear regression and Cox proportional hazards models, adjusted for potential confounders. We performed causal mediation analyses to evaluate whether the effect of thyroid function on CVD is mediated by coagulation. RESULTS: Higher FT4 levels were associated with higher VWF:Ag (ß = 0.34; 95% CI = 0.22, 0.47), lower ADAMTS13 activity (ß = -0.22; 95%CI = -0.35, -0.09), and higher fibrinogen (ß = 0.26; 95% CI = 0.13, 0.39); 857 incident cardiovascular events and 690 cardiovascular deaths occurred. FT4 levels were positively associated with cardiovascular events and deaths. The effect of FT4 on incident cardiovascular events was minimally mediated by fibrinogen (1.6%) but not by VWF:Ag and ADAMTS13. VWF:Ag and fibrinogen together mediated 10.0% of the effect of FT4 on cardiovascular deaths. CONCLUSIONS: Higher FT4 levels were associated with higher VWF:Ag, lower ADAMTS13 activity, and higher fibrinogen levels, indicating a procoagulant state. VWF:Ag and fibrinogen explained up to 10% of the link between FT4 and CVD.

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