Dataset Information

Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults: A Population-Based Cohort Study.

ABSTRACT: Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. Methods and Results Factor V Leiden, prothrombin G20210A and protein-coding variants in the PROC (protein C), PROS1 (protein S), and SERPINC1 (antithrombin) anticoagulant genes were determined in 29 387 subjects (born 1923-1950, 60% women) who participated in the Malmö Diet and Cancer study (1991-1996). The Human Gene Mutation Database was used to define 68 disease-causing mutations. Patients were followed up from baseline until the first event of venous thromboembolism (VTE), death, or Dec 31, 2018. Carriership (n=908, 3.1%) for disease-causing mutations in the PROC, PROS1, and SERPINC1 genes was associated with incident VTE: Hazard ratio (HR) was 1.6 (95% CI, 1.3-1.9). Variants not in Human Gene Mutation Database were not linked to VTE (HR, 1.1; 95% CI, 0.8-1.5). Heterozygosity for rs6025 and rs1799963 was associated with incident VTE: HR, 1.8 (95% CI, 1.6-2.0) and HR, 1.6 (95% CI, 1.3-2.0), respectively. The HR for carrying 1 classical thrombophilia variant was 1.7 (95% CI, 1.6-1.9). HR was 3.9 (95% CI, 3.1-5.0) for carriers of ≥2 thrombophilia variants. Conclusions The 5 classic thrombophilias are associated with a dose-graded risk of VTE in middle-aged and older adults. Disease-causing variants in the PROC, PROS1, and SERPINC1 genes were more common than the rs1799963 variant but the conferred genetic risk was comparable with the rs6025 and rs1799963 variants.

SUBMITTER: Manderstedt E

PROVIDER: S-EPMC9245807 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults: A Population-Based Cohort Study.

Manderstedt Eric E Lind-Halldén Christina C Halldén Christer C Elf Johan J Svensson Peter J PJ Dahlbäck Björn B Engström Gunnar G Melander Olle O Baras Aris A Lotta Luca A LA Zöller Bengt B

Journal of the American Heart Association 20220203 4

Background Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. Methods and Results Factor V Leiden, prothrombin G20210A and protein-coding variants in the PROC (protein C), PROS1 (protein S), and SERPINC1 (antithrombin) anticoagulan ...[more]

PMID: 35112923

Similar Datasets

Project description:BackgroundLifestyle risk behaviors are responsible for a large proportion of disease burden worldwide. Behavioral risk factors, such as smoking, poor diet, and physical inactivity, tend to cluster within populations and may have synergistic effects on health. As evidence continues to accumulate on emerging lifestyle risk factors, such as prolonged sitting and unhealthy sleep patterns, incorporating these new risk factors will provide clinically relevant information on combinations of lifestyle risk factors.Methods and findingsUsing data from a large Australian cohort of middle-aged and older adults, this is the first study to our knowledge to examine a lifestyle risk index incorporating sedentary behavior and sleep in relation to all-cause mortality. Baseline data (February 2006- April 2009) were linked to mortality registration data until June 15, 2014. Smoking, high alcohol intake, poor diet, physical inactivity, prolonged sitting, and unhealthy (short/long) sleep duration were measured by questionnaires and summed into an index score. Cox proportional hazards analysis was used with the index score and each unique risk combination as exposure variables, adjusted for socio-demographic characteristics. During 6 y of follow-up of 231,048 participants for 1,409,591 person-years, 15,635 deaths were registered. Of all participants, 31.2%, 36.9%, 21.4%, and 10.6% reported 0, 1, 2, and 3+ risk factors, respectively. There was a strong relationship between the lifestyle risk index score and all-cause mortality. The index score had good predictive validity (c index = 0.763), and the partial population attributable risk was 31.3%. Out of all 96 possible risk combinations, the 30 most commonly occurring combinations accounted for more than 90% of the participants. Among those, combinations involving physical inactivity, prolonged sitting, and/or long sleep duration and combinations involving smoking and high alcohol intake had the strongest associations with all-cause mortality. Limitations of the study include self-reported and under-specified measures, dichotomized risk scores, lack of long-term patterns of lifestyle behaviors, and lack of cause-specific mortality data.ConclusionsAdherence to healthy lifestyle behaviors could reduce the risk for death from all causes. Specific combinations of lifestyle risk behaviors may be more harmful than others, suggesting synergistic relationships among risk factors.

Project description:Evidence regarding the role of chronic low-grade inflammation in the progression of cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) is currently limited. This prospective cohort study, utilising data from the UK Biobank, included 273,804 adults aged 40-69 years initially free of CMD at baseline. CMM was defined as the coexistence of two or more CMDs, such as coronary artery disease, type 2 diabetes mellitus, hypertension and stroke. The aggregated inflammation score (INFLA-score), incorporating C-reactive protein, white blood cell count, platelet count and granulocyte-to-lymphocyte ratio, quantified chronic low-grade inflammation. Absolute risks (ARs), hazard ratios (HRs) and 95% confidence intervals (CIs) assessed the association of increased INFLA-score with the risk of CMMs and CMDs. The accelerated failure time model explored the effect of INFLA-score on the time to CMM onset, and a restricted cubic spline characterised the dose-dependent relationship between INFLA-score and CMM risk. After a median follow-up of 166.37 months, 13,755 cases of CMM were identified. In quartiles with increasing INFLA-score levels, CMM ARs were 4.41%, 4.49%, 5.04% and 6.01%, respectively; HR increased by 2%, 15% and 36%, respectively, compared to the lowest quartile. The INFLA-score and CMM risk relationship was nonlinear (P for nonlinear < 0.001), exhibiting a significant risk trend change at a score of 9. For INFLA-score < 9, CMM risk increased by 1.9% for each 1-point increase; for INFLA-score ≥ 9, the risk increased by 5.9% for each 1-point increase. Additionally, a higher INFLA-score was associated with an earlier onset of CMM (P < 0.001). Compared to the first INFLA-score quartile, the AFT model revealed adjusted median times to CMM occurrence were 2.92, 6.10 and 13.19 months earlier in the second, third and fourth quartile groups, respectively. Chronic low-grade inflammation is associated with a higher risk of cardiometabolic multimorbidity and earlier onset among middle-aged and older adults. Monitoring and screening the INFLA-score in adults without CMDs may improve early prevention of CMM.

Project description:BackgroundFrailty is a public health problem for ageing society, however, evidence is lacking regarding its impact on intestinal functions. We aimed to examine prospective relationships of frailty and pre-frailty in middle-aged and older adults with incident irritable bowel syndrome (IBS) in a large-scale population-based cohort.MethodsParticipants (aged 37-73 years) free of IBS, coeliac disease, inflammatory bowel disease and any cancer at baseline were included, using data from the UK Biobank (collected 2006-2010, 22 assessment centres). Participants without available primary care data were excluded. Frailty status was assessed using Fried phenotype including five criteria (weight loss, exhaustion, low grip strength, low physical activity, slow walking pace). Participants who met at least three criteria were defined as frail, and those who fulfilled one or two criteria were defined as pre-frail. Primary outcome was incident IBS. Cox proportional hazard model was conducted to examine the associated risk of incident IBS.FindingsAmong 176,423 participants (mean age 56.19 years), 7994 (4.5%) and 78,957 (44.8%) were frail and pre-frail at baseline. During a median of 13.2-year follow-up, 4155 cases of incident IBS were identified. Compared with non-frail individuals, those with frail (HR = 1.80, 95% CI: 1.59-2.04) and pre-frail (HR = 1.21, 1.14-1.30) showed significantly higher risk of developing IBS after multivariable adjustment (Ptrend < 0.001). Specifically, the positive association was not only observed in older adults (HR = 1.69, 1.37-2.08 for frail; 1.24, 1.12-1.39 for pre-frail), but also in middle-aged adults (HR = 1.90, 1.62-2.22 for frail; 1.19, 1.10-1.30 for pre-frail), both with Ptrend < 0.001. Further sensitivity analysis and subgroup analysis indicated similar results.InterpretationFrailty and pre-frailty in middle-aged and older adults are associated with increased risk of incident clinical diagnosis of IBS.FundingNational Natural Science Foundation of China (No. 82070550) & National Key Research and Development Program of China (2022YFC2504002, 2022YFC2504003).

Project description:BackgroundIndoor air pollution has been reported to have adverse effects on the eye; however, the health effects of exposure to cooking with solid fuels on visual impairment remain unclear in China.ObjectiveWe aimed to examine the association between cooking with solid fuels and visual impairment, including distance visual impairment (DVI) and near visual impairment (NVI).MethodsData were obtained from the China Health and Retirement Longitudinal Study, a nationwide survey of adults aged over 45 years who were enrolled in 2011 (Wave 1) and followed up in Wave 2 (2013), Wave 3 (2015), and Wave 4 (2018). We used Cox proportional hazards models to determine the association between solid fuels use and visual impairment. Additionally, the impact of switching cooking fuel types on vision function were examined through wave-specific data analysis (Wave 1 and Wave 4). Interaction and subgroup analyses were performed to explore the potential effect modifiers. Data were collected using the stratified multistage random sampling method and further analyzed using SPSS 27.0 and R 4.2.1 statistical software packages.ResultsA total of 9559 middle-aged and older Chinese adults without visual impairment at baseline were included in the study, with 51.2% (n=4914) of the participants reporting that they cooked with solid fuels. During the follow-up period, 2644 (27.5%) and 3130 (32.6%) participants developed DVI and NVI, respectively. Compared with the clean fuel users, participants who cooked with solid fuels had a higher risk of DVI (hazards ratio [HR] 1.38, 95% CI 1.28-1.50) and NVI (HR 1.18, 95% CI 1.10-1.27). In addition, switching the cooking fuel type from clean to solid fuels was associated with an elevated risk of DVI (HR 1.51, 95% CI 1.15-1.98) and NVI (HR 1.39, 95% CI 1.06-1.82) compared to persistently using clean fuels during the follow-up period, although no protective effect of switching from solid to clean fuels on NVI was found (P=.52). In subgroup analysis, we found that cooking with solid fuels increased the risk of DVI in participants younger than 65 years (HR 1.41, 95% CI 1.28-1.55), men (HR 1.45, 95% CI 1.28-1.65), urban residents (HR 1.41, 95% CI 1.08-1.75), and smokers (HR 1.43, 95% CI 1.25-1.64). By contrast, negative effects of cooking with solid fuels on NVI were found in nonsmokers (HR 1.21, 95% CI 1.11-1.33) and urban residents (HR 1.20, 95% CI 1.10-1.37).ConclusionsCooking with solid fuels was associated with an increased risk of visual impairment among middle-aged and older Chinese adults. These findings indicate that promoting the utilization of clean fuels is conducive to reducing the burden of visual impairment for the public.

Dataset Information

Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults: A Population-Based Cohort Study.

Publications

Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults: A Population-Based Cohort Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets