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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.
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.

3.
Calcif Tissue Int ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31608419

RESUMO

Loop diuretics (LD) may affect bone health by inhibiting renal calcium reuptake. However, whether vitamin D status and dietary calcium intake modify the association between LD and bone outcome is unclear. Therefore, this study aimed to evaluate whether vitamin D level or calcium intake modify the association between LD and various indices of bone health including bone mineral density (BMD) and Trabecular Bone Score (TBS). From The Rotterdam Study, a prospective population-based cohort study, we used data from 6990 participants aged > 45 year with a DXA scan (2002-2008), 6908 participants with femoral neck (FN)-BMD, 6677 participants with lumbar spine (LS)-BMD and 6476 participants with LS-TBS measurements. Use of LD was available from pharmacy dispensing records. Vitamin D (25(OH)D) level was measured in serum, and dietary calcium intake was measured with a validated food frequency questionnaire. Almost eight percent of the participants used LD. The association between LD (past-users compared to never-users) and LS-TBS was significantly different by 25(OH)D concentrations (P for interaction = 0.04). A significantly lower LS-TBS among LD past-users was observed for 25(OH)D ≥ 50 nmol/l compared to ≤ 20 and 20-50 nmol/l (ß = - 0.036, 95% CI - 0.060; - 0.013 vs. ß = - 0.012, 95% CI - 0.036; 0.013 and ß = - 0.031, 95% CI - 0.096; 0.034, respectively). However, no other significant effect modification by 25(OH)D and dietary calcium intake was found in the associations between LD use and bone health outcomes (P-interaction > 0.13). This study suggests that the association between LD use and indices of bone health is not consistently modified by vitamin D or dietary calcium intake.

4.
Int J Cancer ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642518

RESUMO

Complete and accurate registration of cancer is needed to provide reliable data on cancer incidence and to investigate aetiology. Such data can be derived from national cancer registries, but also from large population-based cohort studies. Yet, the concordance and discordance between these two data sources remain unknown. We evaluated completeness and accuracy of cancer registration by studying the concordance between the population-based Rotterdam Study (RS) and the Netherlands Cancer Registry (NCR) between 1989 and 2012 using the independent case ascertainment method. We compared all incident cancers in participants of the RS (aged ≥45 years) to registered cancers in the NCR in the same persons based on the date of diagnosis and the International Classification of Diseases (ICD) code. In total, 2,977 unique incident cancers among 2,685 persons were registered. Two hundred eighty-eight cancers (9.7%) were coded by the RS that were not present in the NCR. These were mostly nonpathology-confirmed lung and haematological cancers. Furthermore, 116 cancers were coded by the NCR, but not by the RS (3.9%), of which 20.7% were breast cancers. Regarding pathology-confirmed cancer diagnoses, completeness was >95% in both registries. Eighty per cent of the cancers registered in both registries were coded with the same date of diagnosis and ICD code. Of the remaining cancers, 344 (14.5%) were misclassified with regard to date of diagnosis and 72 (3.0%) with regard to ICD code. Our findings indicate that multiple sources on cancer are complementary and should be combined to ensure reliable data on cancer incidence.

5.
J Natl Cancer Inst ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498410

RESUMO

BACKGROUND: An emerging body of research suggests that non-central nervous system (CNS) cancer may negatively impact the brain apart from effects of cancer treatment. However, studies assessing cognitive function in newly diagnosed cancer patients cannot exclude selection bias and psychological effects of cancer diagnosis. To overcome these limitations, we investigated trajectories of cognitive function of patients before cancer diagnosis. METHODS: Between 1989 and 2013, 2059 participants from the population-based Rotterdam Study were diagnosed with non-CNS cancer. Cognitive assessments were performed every three-five years using a neuropsychological battery. The general cognitive factor was composed of individual cognitive tests to assess global cognition. Using linear mixed models we compared change in cognitive function of cancer cases before diagnosis with cognitive change of age-matched cancer-free controls (1:2). In addition we performed sensitivity analyses by discarding assessments of controls five years before the end of follow-up to exclude effects from potential undiagnosed cancer. All statistical tests were two-sided. RESULTS: The Word Learning Test immediate recall declined faster among cases than among controls (-0.05 [95%CI=-0.09;-0.01] versus 0.01 [95%CI=-0.01;0.03], P for difference=.003). However, this difference was not statistically significant in sensitivity analyses. Furthermore, no statistically significant differences were observed in change of other individual cognitive tests and of the general cognitive factor. CONCLUSION: In this study we evaluated cognitive function in a large group of cancer patients prior to diagnosis, thereby excluding the psychological impact of cancer diagnosis and biased patient selection. In contrast to previous studies shortly after cancer diagnosis, we found no difference in change of cognitive function between cancer patients and controls.

6.
J Child Adolesc Psychopharmacol ; 29(6): 426-432, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31157978

RESUMO

Objectives: To estimate the number of patients who started methylphenidate during childhood and continued treatment beyond the age of 18 years and to study the determinants that may be associated with continuing treatment. Methods: Patients 17 years of age and younger who have received at least one prescription of methylphenidate were identified in the Integrated Primary Care Information database (1996-2017). Logistic regression analyses were performed to assess the association between potential determinants and continuation with methylphenidate treatment at the age of 18 years. Results: Fifty-three percent of all methylphenidate users (n = 1020) continued their treatment after the age of 18 years. Patients were more likely to continue treatment with methylphenidate if they started treatment at the age of 15-17 years compared with patients of 11 years and younger (adjusted odds ratio [OR]: 5.74, 95% confidence interval [CI]: 1.48-22.31), if they had a medication possession ratio (MPR) between 0.80 and 1.00 compared with a low MPR (adjusted OR: 2.18, 95% CI: 1.23-3.85) and if they lived in an area with a medium level of urbanization (adjusted OR: 1.98, 95% CI: 1.06-3.69). Furthermore, a relatively high number of patients had a MPR >1.0 (24.8%), of whom 91.3% started their treatment when they were between 15 and 17 years of age. Conclusions: Methylphenidate treatment initiated during childhood was continued in half of the study population when reaching the age of 18, where adolescents were more likely to continue treatment than young children. We also found that ∼25% of our study population had a MPR >1, mainly patients 15-17 years of age, which may suggest misuse or abuse of methylphenidate.

7.
PLoS One ; 14(6): e0218115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242253

RESUMO

AIMS: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS: SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS: In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable.

8.
Endocrinology ; 160(7): 1731-1742, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125048

RESUMO

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance-based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall-Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (<2 years). Our data did not support the branched-chain amino acids identified earlier in several US cohorts as potential biomarkers for pancreatic cancer. Thus, although we identified glutamine and histidine as potential biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.

9.
Eur J Nutr ; 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31076856

RESUMO

PURPOSE: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals. METHODS: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA). RESULTS: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per µgmol/L) was associated with a 1.108 kg/m2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention. CONCLUSIONS: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

10.
Br J Nutr ; 122(5): 583-591, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30832747

RESUMO

The role of diet on breast cancer risk is not well elucidated but animal food sources may play a role through, for example, the pathway of the insulin-like growth factor 1 system or cholesterol metabolism. The aim of this study was to evaluate the association between animal foods and the risk of postmenopausal breast cancer. This study was embedded in the Rotterdam Study, a population-based prospective cohort study of subjects aged 55 years and over (61 % female). Dietary intake of different animal foods was assessed at baseline using a validated FFQ and adjusted for energy intake using the residual method. We performed Cox proportional hazards modelling to analyse the association between the intake of the different food sources and breast cancer risk after adjustment for socio-demographic, lifestyle and metabolic factors. During a median follow-up of 17 years, we identified 199 cases of breast cancer (6·2 %) among 3209 women. After adjustment for multiple confounders, no consistent association was found between the intake of red meat intake, poultry, fish or dairy products and breast cancer risk. However, we found that egg intake was significantly associated with a higher risk of breast cancer (hazard ratioQ4 v. Q1: 1·83; 95 % CI 1·20, 2·79; Ptrend=0·01). In conclusion, this study found that dietary egg intake but no other animal foods was associated with a higher risk of postmenopausal breast cancer. Further research on the potential mechanisms underlying this association is warranted.

11.
Int J Cancer ; 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30924141

RESUMO

Several studies found that the systemic immune-inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population-based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow-up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow-up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 [95% CI; 1.11-1.53]), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10-year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p-value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow-up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.

12.
Br J Clin Pharmacol ; 85(5): 993-1002, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30838685

RESUMO

AIMS: There are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes. METHODS: Using the prospective population-based Rotterdam Study, we included 9535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross-sectional associations between statin use and glycaemic traits including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow-up study, we applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins. RESULTS: The mean age at baseline was 64.3 ± 10.1 years and 41.7% were men. In the fully adjusted model, compared to never users of statins, baseline use of statins was associated with higher concentrations of serum fasting insulin (ß = 0.07; 95% CI: 0.02-0.13) and insulin resistance (ß = 0.09; 95% CI: 0.03-0.14). Ever use of statins was associated with a 38% higher risk of incident type 2 diabetes (HR = 1.38; 95% CI: 1.09-1.74). This risk was more prominent in subjects with impaired glucose homeostasis and in overweight/obese individuals. CONCLUSIONS: Individuals using statins may be at higher risk for hyperglycaemia, insulin resistance and eventually type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.

13.
Pharmacoepidemiol Drug Saf ; 28(4): 452-459, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30838712

RESUMO

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used during pregnancy. Findings that prenatal NSAID exposure may affect offspring neurodevelopment have been inconsistent. We investigated the effect of prenatal NSAID exposure on childhood neurodevelopment and explored the susceptibility of our effect estimates to forms of bias via negative exposure, negative outcome, and multi-informant analyses. METHODS: In a cohort of pregnant women (n = 6876), perinatal NSAID use was assessed by prescriptions and self-report. Primary neurodevelopmental outcomes included attention problems using maternal reports at 1½, 3, and 5 years. To explore potential systematic biases, we compared estimates from maternally reported attention problems to a teacher's report and a measure of nonverbal intelligence assessed at a clinic visit at age 6 years; we also used NSAID use before pregnancy and somatic problems as a "negative" exposure and outcome, respectively. RESULTS: Maternal reports suggested that prenatal exposure to NSAIDs was associated with more attention problems at younger ages (eg, at age 3: mean difference in attention problems score: 0.30; 95% CI 0.12, 0.48). However, no strong association with attention problems was found in the teacher report, and a similarly strong association between prenatal NSAID exposure and somatic complaints suggests residual confounding by indication likely remains. Moreover, prenatal exposure to NSAIDs was not associated with an observed measure of IQ (mean difference in IQ score: -0.32; 95% CI: -1.82, 1.19). CONCLUSIONS: Jointly, our results suggest that the observed associations between prenatal exposure to NSAIDs and child attention problems reflect systematic biases of a null or small effect.

14.
PLoS Med ; 16(2): e1002741, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30716101

RESUMO

BACKGROUND: Non-communicable diseases (NCDs) are leading causes of premature disability and death worldwide. However, the lifetime risk of developing any NCD is unknown, as are the effects of shared common risk factors on this risk. METHODS AND FINDINGS: Between July 6, 1989, and January 1, 2012, we followed participants from the prospective Rotterdam Study aged 45 years and older who were free from NCDs at baseline for incident stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease. We quantified occurrence/co-occurrence and remaining lifetime risk of any NCD in a competing risk framework. We additionally studied the lifetime risk of any NCD, age at onset, and overall life expectancy for strata of 3 shared risk factors at baseline: smoking, hypertension, and overweight. During 75,354 person-years of follow-up from a total of 9,061 participants (mean age 63.9 years, 60.1% women), 814 participants were diagnosed with stroke, 1,571 with heart disease, 625 with diabetes, 1,004 with chronic respiratory disease, 1,538 with cancer, and 1,065 with neurodegenerative disease. NCDs tended to co-occur substantially, with 1,563 participants (33.7% of those who developed any NCD) diagnosed with multiple diseases during follow-up. The lifetime risk of any NCD from the age of 45 years onwards was 94.0% (95% CI 92.9%-95.1%) for men and 92.8% (95% CI 91.8%-93.8%) for women. These risks remained high (>90.0%) even for those without the 3 risk factors of smoking, hypertension, and overweight. Absence of smoking, hypertension, and overweight was associated with a 9.0-year delay (95% CI 6.3-11.6) in the age at onset of any NCD. Furthermore, the overall life expectancy for participants without these risk factors was 6.0 years (95% CI 5.2-6.8) longer than for those with all 3 risk factors. Participants aged 45 years and older without the 3 risk factors of smoking, hypertension, and overweight at baseline spent 21.6% of their remaining lifetime with 1 or more NCDs, compared to 31.8% of their remaining life for participants with all of these risk factors at baseline. This difference corresponds to a 2-year compression of morbidity of NCDs. Limitations of this study include potential residual confounding, unmeasured changes in risk factor profiles during follow-up, and potentially limited generalisability to different healthcare settings and populations not of European descent. CONCLUSIONS: Our study suggests that in this western European community, 9 out of 10 individuals aged 45 years and older develop an NCD during their remaining lifetime. Among those individuals who develop an NCD, at least a third are subsequently diagnosed with multiple NCDs. Absence of 3 common shared risk factors is associated with compression of morbidity of NCDs. These findings underscore the importance of avoidance of these common shared risk factors to reduce the premature morbidity and mortality attributable to NCDs.


Assuntos
Expectativa de Vida/tendências , Multimorbidade/tendências , Doenças não Transmissíveis/epidemiologia , Vigilância da População , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doenças não Transmissíveis/terapia , Vigilância da População/métodos , Estudos Prospectivos , Fatores de Risco
15.
Eur J Epidemiol ; 34(5): 463-470, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30569368

RESUMO

Inflammation is a risk factor for morbidity and mortality in the elderly. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that integrates the information of the leukocyte differentials into one variable. We aimed to assess whether the NLR is a risk indicator for overall and cause-specific mortality in the general population. We analyzed data (2002-2014) from the Rotterdam Study, a long-standing, population-based, prospective cohort study in a community-dwelling ageing population. The association between the NLR and time to all-cause mortality was assessed with Cox proportional hazard models. We additionally assessed cardiovascular, cancer and other mortality. The multivariable analyses were adjusted for age, gender, socio-economic status (SES), smoking status, body mass index, type 2 diabetes, and history of cancer and cardiovascular disease (CVD). Data of 8715 individuals were included. The mean age was 65.9 years (SD 10.5) and the majority were women (57.1%). The NLR was higher in men, higher age categories, smokers and among individuals with lower SES, prevalent diabetes, or a history of cancer or CVD. During the 11.7 years follow-up period, 1641 individuals died. Survival among individuals in the 3rd, 4th, and 5th quintile of the NLR was significantly poorer than that of those in the 1st quintile (P < 0.001). In the multivariable analysis, NLR levels were independently and significantly associated with an increased risk of all-cause mortality (HR 1.64; 95% CI 1.44-1.86), cardiovascular mortality (HR 1.92; 95% CI 1.49-2.48), and other mortality (HR 1.86; 95% CI 1.54-2.24). No significant association was found for cancer mortality (HR 1.20; 95% CI 0.95-1.51). The NLR is a strong and independent risk indicator for mortality in the elderly population. Its clinical value needs to be established in further studies.


Assuntos
Linfócitos , Mortalidade , Neutrófilos , Idoso , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos
16.
Artigo em Inglês | MEDLINE | ID: mdl-30341095

RESUMO

BACKGROUND: Folic acid and vitamin-B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin-B12 on the incidence of overall cancer and on colorectal cancer in the B-PROOF trial. METHODS: Long-term follow-up of B-PROOF trial participants (N=2,524), a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 µg) and vitamin-B12 (500 µg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for CRC. RESULTS: Allocation to B-vitamins was associated with a higher risk of overall cancer (171 [13.6%] vs. 143 [11.3%]), HR 1.25; 95%CI 1.00-1.53, p=0.05). B-vitamins were significantly associated with a higher risk of colorectal cancer (43[3.4%] vs. 25[2.0%]), HR 1.77; 95%CI 1.08-2.90, p=0.02). CONCLUSION: Folic acid and vitamin-B12 supplementation was associated with an increased risk of colorectal cancer. IMPACT: Our findings suggest that folic acid and vitamin-B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin-B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication such as a proven deficiency.

17.
Int J Cardiol ; 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30268382

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with atrial fibrillation (AF). More insight into the epidemiology and underlying mechanisms is required to optimize management. METHODS: The Rotterdam Study is a large, population-based cohort study with long-term follow-up. Time dependent Cox proportional hazard models were constructed to study the effect of COPD on incident AF, adjusted for age, sex and pack years of cigarette smoking, and additionally stratified according to exacerbation frequency, left atrial size and baseline systemic inflammatory levels. RESULTS: 1369 of 10,943 subjects had COPD, of whom 804 developed AF. The AF incidence rate was 14 per 1000 person years in COPD and 8 per 1000 person years in subjects without COPD. The adjusted hazard ratio (HR) for COPD subjects to develop AF as compared to subjects without COPD was 1.28 (95%CI [1.04, 1.57]). COPD subjects with frequent exacerbations had a twofold increased AF risk (HR 1.99 [1.42, 2.79]) and COPD subjects with a left atrial size ≥40 mm also had an elevated AF risk (HR 1.77 [1.07, 2.94]). COPD subjects with baseline systemic inflammatory levels above the median had significantly increased AF risks (hsCRP≥1.83 mg/L: HR 1.51 [1.13, 2.03] and IL6 ≥ 1.91 ng/L: HR 2.49 [1.18, 5.28]), whereas COPD subjects below the median had in both analyses no significantly increased AF risk. CONCLUSIONS: COPD subjects had a 28% increased AF risk, which further increased with frequent exacerbations and an enlarged left atrium. The risk was driven by COPD subjects having elevated systemic inflammatory levels.

18.
Eur Heart J ; 39(44): 3961-3969, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30169657

RESUMO

Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

19.
Br J Nutr ; 120(10): 1159-1170, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30205856

RESUMO

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (P race difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (P race difference=0·56). Among EA, the 25(OH)D-FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

20.
Eur Respir J ; 52(4)2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30139775

RESUMO

Optimal survival benefit from different lines of anticancer treatment in advanced nonsmall cell lung cancer (NSCLC) requires conservation of renal function. We evaluated the development of renal impairment during pemetrexed maintenance.In a prospective multicentre cohort study, we evaluated the incidence of acute/chronic kidney disease (AKD/CKD), its related treatment discontinuation frequency and associated clinical variables with AKD in patients with stage IIIB/IV NSCLC treated with pemetrexed maintenance. We validated the findings in an independent cohort.190 patients received pemetrexed. In the primary cohort, 149 patients started induction, of whom 44 patients (30%) continued maintenance. In the independent cohort, 41 patients received maintenance. During maintenance 13 patients (30%) developed AKD, leading to CKD and treatment discontinuation in eight patients (62%) in the primary cohort. Higher estimated glomerular filtration rate (eGFR) (per unit 5 mL·min-1 per 1.73 m2) before maintenance and induction (OR 0.70, 95% CI 0.54-0.90 and OR 0.78, 95% CI 0.62-0.98, respectively) and relative decline (per 10%) in eGFR during induction (OR 2.54, 95% CI 1.36-4.74) were associated with AKD during maintenance. In the independent cohort, 20 patients (49%) developed AKD, leading to CKD in 11 patients (55%) and treatment discontinuation in six patients (30%).Patients are at risk for renal impairment during pemetrexed maintenance, which may jeopardise further lines of anticancer treatment.

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