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2.
Eur J Neurol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590563

RESUMO

BACKGROUND: Chronic axonal polyneuropathy is a common, usually multifactorial disease and there is no treatment available yet. We investigated the association between cardiovascular health, defined by the health score of the American Heart Association, and chronic axonal polyneuropathy. METHODS: Between June 2013 and January 2017, we investigated participants of the Rotterdam Study, a population-based cohort study. Participants were screened for polyneuropathy and categorized as no, possible, probable or definite polyneuropathy. The cardiovascular health score (range 0-14, higher score reflecting better health) consisted of four health behaviours (diet, physical activity, smoking and body mass index) and three health factors (blood pressure, serum cholesterol and fasting glucose level). RESULTS: We included 1919 participants of whom 120 (6.3%) had definite polyneuropathy. Median age was 69.0 years (IQR 58.6-73.7) and 53.4% was female. A higher cardiovascular health score was associated with a lower prevalence of definite polyneuropathy (per point increase: OR 0.90, 95%CI 0.84-0.96). Optimal cardiovascular health (score≥10) was strongly associated with lower prevalence of definite polyneuropathy (OR 0.55, 95%CI 0.32-0.90). An increase of health factors and health behaviour score separately was associated with a lower prevalence of polyneuropathy (per point increase: OR 0.82, 95%CI 0.71-0.95 and OR 0.86, 95%CI 0.78-0.96, respectively). The association between a lower cardiovascular health score and lower sural nerve amplitude was not significant after correction for covariates (difference 0.07µV, 95%CI -0.02;0.17). CONCLUSIONS: Better cardiovascular health, consisting of both modifiable health behaviours and health factors, is associated with a lower prevalence of chronic axonal polyneuropathy.

3.
Eur J Prev Cardiol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33564885

RESUMO

AIMS: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies. METHODS AND RESULTS: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%). CONCLUSION: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI.

4.
BMC Med Genomics ; 14(1): 45, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568140

RESUMO

BACKGROUND: Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control. RESULTS: On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls. CONCLUSIONS: We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI.

5.
BMC Med ; 19(1): 43, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33588853

RESUMO

BACKGROUND: Despite the growing burden of heart failure (HF), there have been no recommendations for use of any of the primary prevention models in the existing guidelines. HF was also not included as an outcome in the American College of Cardiology/American Heart Association (ACC/AHA) risk score. METHODS: Among 2743 men and 3646 women aged ≥ 55 years, free of HF, from the population-based Rotterdam Study cohort, 4 Cox models were fitted using the predictors of the ACC/AHA, ARIC and Health-ABC risk scores. Performance of the models for 10-year HF prediction was evaluated. Afterwards, performance and net reclassification improvement (NRI) for adding NT-proBNP to the ACC/AHA model were assessed. RESULTS: During a median follow-up of 13 years, 429 men and 489 women developed HF. The ARIC model had the highest performance [c-statistic (95% confidence interval [CI]): 0.80 (0.78; 0.83) and 0.80 (0.78; 0.83) in men and women, respectively]. The c-statistic for the ACC/AHA model was 0.76 (0.74; 0.78) in men and 0.77 (0.75; 0.80) in women. Adding NT-proBNP to the ACC/AHA model increased the c-statistic to 0.80 (0.78 to 0.83) in men and 0.81 (0.79 to 0.84) in women. Sensitivity and specificity of the ACC/AHA model did not drastically change after addition of NT-proBNP. NRI(95%CI) was - 23.8% (- 19.2%; - 28.4%) in men and - 27.6% (- 30.7%; - 24.5%) in women for events and 57.9% (54.8%; 61.0%) in men and 52.8% (50.3%; 55.5%) in women for non-events. CONCLUSIONS: Acceptable performance of the model based on risk factors included in the ACC/AHA model advocates use of this model for prediction of HF risk in primary prevention setting. Addition of NT-proBNP modestly improved the model performance but did not lead to relevant discrimination improvement in clinical risk reclassification.

6.
Circ Cardiovasc Imaging ; 13(11): e010340, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33190533

RESUMO

BACKGROUND: Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated. METHODS: We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies. RESULTS: Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5-12.2] versus odds ratio, 1.2 [95% CI, 0.6-2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8-8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia. CONCLUSIONS: Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age. Registration: URL: https://www.trialregister.nl/trial/5406; Unique identifier: NTR5531.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33214188

RESUMO

INTRODUCTION: Pre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population. RESEARCH DESIGN AND METHODS: We used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death. RESULTS: Out of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively. CONCLUSION: Prevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33151443

RESUMO

PURPOSE: Breast cancer treatment has been associated with vascular pathology. It is unclear if such treatment is also associated with long-term cerebrovascular changes. We studied the association between radiotherapy and chemotherapy with carotid pathology and brain perfusion in breast cancer survivors. METHODS: We included 173 breast cancer survivors exposed to radiotherapy and chemotherapy, assessed ± 21.2 years after cancer diagnosis, and 346 age-matched cancer-free women (1:2) selected from the population-based Rotterdam Study. Outcome measures were carotid plaque score, intima-media thickness (IMT), total cerebral blood flow (tCBF), and brain perfusion. Additionally, we investigated the association between inclusion of the carotid artery in the radiation field (no/small/large part), tumor location, and these outcome measures within cancer survivors. RESULTS: Cancer survivors had lower tCBF (- 19.6 ml/min, 95%CI - 37.3;- 1.9) and brain perfusion (- 2.5 ml/min per 100 ml, 95%CI - 4.3;- 0.7) than cancer-free women. No statistically significant group differences were observed regarding plaque score or IMT. Among cancer survivors, a large versus a small part of the carotid artery in the radiation field was associated with a higher IMT (0.05, 95%CI0.01;0.09). Also, survivors with a right-sided tumor had lower left carotid plaque score (- 0.31, 95%CI - 0.60;- 0.02) and higher brain perfusion (3.5 ml/min per 100 ml, 95%CI 0.7;6.2) than those with a left-sided tumor. CONCLUSIONS: On average two decades post-diagnosis, breast cancer survivors had lower tCBF and brain perfusion than cancer-free women. Also, survivors with a larger area of the carotid artery within the radiation field had a larger IMT. Future studies should confirm if these cerebrovascular changes underlie the frequently observed cognitive problems in cancer survivors.

9.
JAMA Cardiol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146689

RESUMO

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P < .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein. Conclusions and Relevance: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.

10.
Front Oncol ; 10: 1700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042813

RESUMO

Background: Atherosclerosis and cancer share multiple disease pathways. Yet, it is unclear if atherosclerosis is associated with a subsequent higher cancer risk. We determined the association of atherosclerotic calcification in the aortic arch, as proxy for systemic atherosclerosis, with the risk of cancer. Methods: Between 2003 and 2006, 2,404 participants (mean age: 69.5 years, 52.5% women) from the prospective population-based Rotterdam Study underwent computed tomography to quantify calcification in the aortic arch. Participants were followed for the onset of cancer, death, loss to follow-up, or January 1st, 2015, whichever came first. We computed sex-specific tertiles of aortic arch calcification volumes. Next, we examined the association between the volume and severity (i.e., tertiles) of aortic arch calcification and the risk of cancer using Cox proportional hazard models. Results: During a median (interquartile range) follow-up of 9.6 years (8.9-10.5), 348 participants were diagnosed with cancer. Participants with the greatest severity of aortic arch calcification had a higher risk of cancer [hazard ratio for the third tertile compared to the first tertile of aortic arch calcification volume in the total population is 1.39 (95% CI = 1.04-1.86)]. Conclusions: Individuals with the most severe aortic arch calcification had a higher risk of cancer. While this could reflect the impact of long-term exposure to shared risk factors, it might also point toward the co-occurrence of both conditions.

11.
Clin Epigenetics ; 12(1): 157, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092652

RESUMO

BACKGROUND: Tobacco smoking is a well-known modifiable risk factor for many chronic diseases, including cardiovascular disease (CVD). One of the proposed underlying mechanism linking smoking to disease is via epigenetic modifications, which could affect the expression of disease-associated genes. Here, we conducted a three-way association study to identify the relationship between smoking-related changes in DNA methylation and gene expression and their associations with cardio-metabolic traits. RESULTS: We selected 2549 CpG sites and 443 gene expression probes associated with current versus never smokers, from the largest epigenome-wide association study and transcriptome-wide association study to date. We examined three-way associations, including CpG versus gene expression, cardio-metabolic trait versus CpG, and cardio-metabolic trait versus gene expression, in the Rotterdam study. Subsequently, we replicated our findings in The Cooperative Health Research in the Region of Augsburg (KORA) study. After correction for multiple testing, we identified both cis- and trans-expression quantitative trait methylation (eQTM) associations in blood. Specifically, we found 1224 smoking-related CpGs associated with at least one of the 443 gene expression probes, and 200 smoking-related gene expression probes to be associated with at least one of the 2549 CpGs. Out of these, 109 CpGs and 27 genes were associated with at least one cardio-metabolic trait in the Rotterdam Study. We were able to replicate the associations with cardio-metabolic traits of 26 CpGs and 19 genes in the KORA study. Furthermore, we identified a three-way association of triglycerides with two CpGs and two genes (GZMA; CLDND1), and BMI with six CpGs and two genes (PID1; LRRN3). Finally, our results revealed the mediation effect of cg03636183 (F2RL3), cg06096336 (PSMD1), cg13708645 (KDM2B), and cg17287155 (AHRR) within the association between smoking and LRRN3 expression. CONCLUSIONS: Our study indicates that smoking-related changes in DNA methylation and gene expression are associated with cardio-metabolic risk factors. These findings may provide additional insights into the molecular mechanisms linking smoking to the development of CVD.

12.
BMC Med ; 18(1): 263, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32967688

RESUMO

BACKGROUND: Evidence has pointed towards differences in the burden of arteriosclerosis according to its location and sex. Yet there is a scarcity of population-based data on aggregated sex-specific cardiovascular risk profiles, instead of single risk factors, and mortality risk according to the location of arteriosclerosis. We assessed sex-specific cardiovascular risk profiles and mortality risk associated with arteriosclerosis. METHODS: From the population-based Rotterdam Study, 2357 participants (mean age 69 years, 53% women) underwent non-contrast computed tomography to quantify calcification, as a proxy for arteriosclerosis, in the coronary arteries (CAC), aortic arch (AAC), extracranial (ECAC) and intracranial carotid arteries (ICAC), vertebrobasilar arteries (VBAC), and aortic valve (AVC). Principal component analysis (PCA) of eight distinct cardiovascular risk factors was performed, separately for women and men, to derive risk profiles based on the shared variance between factors. We used sex-stratified multivariable logistic regression to examine the associations between PCA-derived risk profiles and severe calcification at different locations. We investigated the associations of severe calcification with mortality risk using sex-stratified multivariable Cox regression. RESULTS: PCA identified three cardiovascular risk profiles in both sexes: (1) anthropometry, glucose, and HDL cholesterol; (2) blood pressure; and (3) smoking and total cholesterol. In women, the strongest associations were found for profile 2 with severe ECAC and ICAC (adjusted OR [95% CI] 1.32 [1.14-1.53]) and for profile 3 with severe at all locations, except AVC. In men, the strongest associations were found for profile 2 with VBAC (1.31 [1.12-1.52]) and profile 3 with severe AAC (1.28 [1.09-1.51]). ECAC and AVC in women and CAC in men showed the strongest, independent associations with cardiovascular mortality (HR [95% CI] 2.11 [1.22-3.66], 2.05 [1.21-3.49], 2.24 [1.21-3.78], respectively). CONCLUSIONS: Our findings further underline the existence of sex- and location-specific differences in the etiology and consequences of arteriosclerosis. Future research should unravel which distinct pathological processes underlie differences in risk profiles for arteriosclerosis.

13.
Eur J Prev Cardiol ; : 2047487320941993, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32726563

RESUMO

BACKGROUND: Tobacco use is the single largest preventable risk factor for premature death of non-communicable diseases and the second leading cause of cardiovascular disease. In response to the harmful effects of tobacco smoking, the use of electronic cigarettes (e-cigarettes) has emerged and gained significant popularity over the past 15 years. E-cigarettes are promoted as safe alternatives for traditional tobacco smoking and are often suggested as a way to reduce or quit smoking. However, evidence suggests they are not harmless. DISCUSSION: The rapid evolution of the e-cigarette market has outpaced the legislator's regulatory capacity, leading to mixed regulations. The increasing use of e-cigarettes in adolescents and young individuals is of concern. While the long-term direct cardiovascular effects of e-cigarettes remain largely unknown, the existing evidence suggests that the e-cigarette should not be regarded as a cardiovascular safe product. The contribution of e-cigarette use to reducing conventional cigarette use and smoking cessation is complex, and the impact of e-cigarette use on long-term cessation lacks sufficient evidence. CONCLUSION: This position paper describes the evidence regarding the prevalence of e-cigarette smoking, uptake of e-cigarettes in the young, related legislations, cardiovascular effects of e-cigarettes and the impact of e-cigarettes on smoking cessation. Knowledge gaps in the field are also highlighted. The recommendations from the population science and public health section of the European Association of Preventive Cardiology are presented.

14.
Genet Med ; 22(11): 1803-1811, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32624571

RESUMO

PURPOSE: We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)-associated variants (PRS313) and other, nongenetic risk factors. METHODS: Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS313 was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS313 and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS313). C-statistics were used to evaluate discriminative ability. RESULTS: In total, 320 women developed BC. The PRS313 was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40-1.73]). Using 10-year risk estimates including age and the PRS313, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653. CONCLUSIONS: The effect size of the PRS313 is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population.

15.
Eur J Epidemiol ; 35(5): 483-517, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367290

RESUMO

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.


Assuntos
Doença Crônica/epidemiologia , Expectativa de Vida/tendências , Vigilância da População/métodos , Adulto , Estudos de Coortes , Projetos de Pesquisa Epidemiológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Risco
16.
PLoS Med ; 17(5): e1003115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379748

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association. METHODS AND FINDINGS: Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity. CONCLUSIONS: In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.


Assuntos
Imunidade Adaptativa/imunologia , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Imunidade Inata/imunologia , Idoso , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia
17.
J Clin Endocrinol Metab ; 105(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271379

RESUMO

CONTEXT: There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease. OBJECTIVE: To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D). DESIGN: 3089 samples from individuals with T2D, collected between 1999 and 2015, from 5 independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1100 individuals from 2 of the cohorts. MAIN OUTCOME MEASURES: Plasma metabolites (n = 149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing. RESULTS: In total, 125 metabolites were significantly associated (PFDR = 1.5×10-32 - 0.046; ß = -11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids (AAAs), glycoprotein acetyls, triglycerides (TGs), lipids in very low-density lipoproteins (VLDL) subclasses, and fatty acids (PFDR < 0.03). We observed positive associations with cholesterol and phospholipids in high-density lipoproteins (HDL) and apolipoprotein A1 (PFDR < 0.05). Albeit some metabolites were associated with UACR levels (P < 0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr = 0.003; PHDLrelated < 0.05), but not after. CONCLUSIONS: This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32118043

RESUMO

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is one of the most frequent cardiovascular diseases among both women and men. Although age-adjusted AF incidence and prevalence is larger among men, women are older at the time of AF diagnosis and have larger risk for AF-associated adverse outcomes such as morality and stroke. Based on evidence from epidemiological studies, elevated body mass index seems to confer a higher risk of AF among men. However, evidence regarding sex differences in the association between diabetes mellitus, elevated blood pressure, and dysglycemia with AF remains conflicting. While men with AF have larger burden of coronary artery disease, women with AF tend to have a larger prevalence of heart failure and valvular heart disease. Recently, several women-specific risk factors including pregnancy and its complications and number of children have been associated with AF. Earlier age at menopause, despite being a strong marker of adverse cardiometabolic risk, does not seem to be associated with increased risk of AF. To reduce the AF burden in both genders, better understanding of the differences between women and men with regard to AF is central. Large-scale studies are needed to separately investigate and report on women and men. Besides observations from epidemiological and clinical studies, to improve our understanding of sexual dimorphism in AF, sufficiently large genome-wide association studies as well as well-powered Mendelian randomization studies are essential to shed light on the sex-specific nature of the associations of risk factors with AF.

19.
Eur J Vasc Endovasc Surg ; 59(5): 740-747, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115359

RESUMO

OBJECTIVE: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. METHODS: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. RESULTS: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54). CONCLUSION: After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key.


Assuntos
Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares , Fatores Etários , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida
20.
Front Genet ; 11: 110, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174972

RESUMO

MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and coronary heart disease (CHD) using single-omics data, but much less by leveraging population-based omics data. Here we aimed to conduct a multi-omics analysis to identify miRNAs associated with cardiometabolic risk factors and diseases. First, we used publicly available summary statistics from large-scale genome-wide association studies to find genetic variants in miRNA-related sequences associated with various cardiometabolic traits, including lipid and obesity-related traits, glycemic indices, blood pressure, and disease prevalence of T2D and CHD. Then, we used DNA methylation and miRNA expression data from participants of the Rotterdam Study to further investigate the link between associated miRNAs and cardiometabolic traits. After correcting for multiple testing, 180 genetic variants annotated to 67 independent miRNAs were associated with the studied traits. Alterations in DNA methylation levels of CpG sites annotated to 38 of these miRNAs were associated with the same trait(s). Moreover, we found that plasma expression levels of 8 of the 67 identified miRNAs were also associated with the same trait. Integrating the results of different omics data showed miR-10b-5p, miR-148a-3p, miR-125b-5p, and miR-100-5p to be strongly linked to lipid traits. Collectively, our multi-omics analysis revealed multiple miRNAs that could be considered as potential biomarkers for early diagnosis and progression of cardiometabolic diseases.

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