Lifestyle Moderates Genetic Risk of Venous Thromboembolism

Objective: Venous thromboembolism (VTE) is a common disease that has a genetic basis. Lifestyle factors contribute to risk, but it is unknown whether healthy lifestyle can mitigate the genetic risk. We studied whether greater adherence to the American Heart Association’s cardiovascular health metric, Life’s Simple 7 (LS7), is associated with lower incidence of VTE in individuals across categories of a genetic risk score (GRS) for VTE. Approach AND RESULTS: We followed 9026 White participants from the ARIC (Atherosclerosis Risk in Communities) Study, a prospective cohort enrolled in 1987 to 1989 until 2015. We tested the joint associations with VTE of a validated VTE GRS comprising 5 well-known gene variants and baseline LS7 categories. There were 466 incident VTE events over 22.8 years. Participants with an optimal LS7 score had a lower incidence of VTE (3.9%) than those with inadequate LS7 (5.7%). Compared with the high GRS and inadequate LS7 group (hazard ratio=1), those with high GRS and optimal LS7 indeed had a reduced hazard ratio of VTE: 0.65 (95% CI, 0.48–0.89). The group with low GRS and optimal LS7 had the lowest hazard ratio of VTE (0.39 [95% CI, 0.25–0.61]). Of the LS7 components, in all GRS groups, the factor most strongly protective for VTE was normal weight. Conclusions: Among people at low or high genetic risk for VTE, healthier lifestyle factors, particularly normal weight, were associated with a lower incidence of VTE. Further studies should determine the impact of lifestyle changes among patients at high genetic risk of VTE, such as in thrombophilic families.

Download Full-text

Mitigation of Venous Thromboembolism Risk through Favorable Lifestyle: The ARIC Study

Blood ◽

10.1182/blood-2019-131290 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1151-1151

Author(s):

Christina Evans ◽

Ching-Png Hong ◽

Aaron R Folsom ◽

Susan Heckbert ◽

Nicholas Smith ◽

...

Keyword(s):

Venous Thromboembolism ◽

Genetic Risk ◽

Genetic Risk Score ◽

Lifestyle Factors ◽

Normal Weight ◽

Common Disease ◽

High Genetic Risk ◽

Optimal Health ◽

Aric Study ◽

The Impact

Background: Venous thromboembolism (VTE) is a common disease with a strong genetic basis. Unhealthy lifestyle factors contribute to risk, but it is unknown whether healthier lifestyle can mitigate the risk for VTE in those at high genetic risk. We studied whether greater adherence to the American Heart Association's (AHA's) cardiovascular health metric called Life's Simple 7 (LS7) is associated with a lower rate of VTE in individuals with high genetic risk score (GRS) for VTE. Methods: We followed 9,026 middle-aged white participants from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort of 15,792 individuals enrolled in 1987-89. A validated GRS was used, comprising 5 well known genetic conditions associated with VTE (factor V Leiden, prothrombin 20210A, non-O blood group, factor XI rs4241824, and fibrinogen gamma FGG rs2066865). Only white participants were included, as the GRS did not predict VTE in others. AHA's LS7 categories of inadequate, average, and optimal health were determined based on smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. VTE events were adjudicated by expert medical record review. We calculated hazard ratios (HRs) and 95% confidence intervals (CI) of incident VTE by LS7 categories, stratified by GRS (low, intermediate, high), adjusting for age, sex, and education. HRs were also calculated for individual LS7 components stratified by GRS. Results: There were 466 incident VTE over 22.8 years of follow-up. Compared to those with optimal health, those with inadequate LS7 score had higher rates of VTE (5.7% vs. 3.9%). In Figure 1, compared to the high GRS / inadequate LS7 group, the HR of VTE in the low GRS group with optimal health was lowest at 0.39 (95% CI 0.25-0.61), but moreover, the HR in the high GRS group with optimal health was also attenuated to 0.65 (95% CI 0.48-0.89). The pattern of association was similar for provoked and unprovoked VTE. Of the LS7 components, obesity was most strongly related to VTE. In Figure 2, compared to obese / high GRS participants, the HR of VTE with normal weight / low GRS was 0.36 (95% CI 0.23-0.57), while the HR in high GRS / normal weight participants was reduced by 45%, at 0.55 (95% CI 0.4-0.76). Conclusion: Among all participants, even those at high genetic risk, healthier lifestyle factors, particularly obesity, were associated with decreased incidence of VTE. Further studies should determine the impact of lifestyle change among patients at high genetic risk of VTE, such as in thrombophilic families. Disclosures Heckbert: National Institutes of Health: Other: Grants.

Download Full-text

Progression From No AMD to Intermediate AMD as Influenced by Antioxidant Treatment and Genetic Risk

Journal of VitreoRetinal Diseases ◽

10.1177/2474126416680931 ◽

2017 ◽

Vol 1 (1) ◽

pp. 45-51

Author(s):

Carl C. Awh ◽

Brent Zanke ◽

Rafal Kustra

Keyword(s):

Genetic Risk ◽

Factor H ◽

Complement Factor ◽

Antioxidant Treatment ◽

Risk Alleles ◽

High Genetic Risk ◽

Age Related ◽

Allele Dosage ◽

Risk Of Progression ◽

The Impact

Purpose: To investigate the impact of antioxidant treatment and genetic risk on the development of intermediate age-related macular degeneration (AMD) in patients without baseline AMD, using data from the Age-Related Eye Disease Study (AREDS) Cataract Trial. Methods: Genetic risk and antioxidant treatment were analyzed as independent and interacting risk factors for the development of intermediate AMD in 554 AREDS individuals for whom genotyping was available. Genetic risk was determined using an allele dosage model based on the total number of complement factor H and age-related maculopathy sensitivity 2 risk alleles. Results: Overall, 14% of patients developed intermediate AMD over approximately 8 years. The risk of developing intermediate AMD varied from 6.5% for patients with 0 risk alleles to 39% for those with 3 or 4 risk alleles ( P < .0001). Antioxidants had no impact on the development of intermediate AMD overall. However, antioxidant treatment had a significant impact on progression to intermediate AMD for patients with low or high genetic risk. Patients with 0 or 1 risk alleles had increased risk of progression to intermediate AMD (hazard ratio [HR] = 2.31, P = .017) if treated with antioxidants compared to placebo. Patients with 3 or 4 risk alleles had decreased risk of progression to intermediate AMD (HR = 0.27, P = .0008) if treated with antioxidants compared to placebo. Conclusion: On average, antioxidant treatment has no impact on the development of intermediate AMD in patients without AMD. However, antioxidant treatment may increase the risk of developing intermediate AMD in patients with low genetic risk and may reduce the risk of developing intermediate AMD in patients with high genetic risk. Since patients with high genetic risk have the greatest risk of progressing from intermediate to advanced AMD, genotype-directed antioxidant treatment of patients without AMD may ultimately lead to fewer cases of advanced AMD.

Download Full-text

Prediction of Venous Thromboembolism Based on Clinical and Genetic Factors

10.1101/2020.03.05.20031054 ◽

2020 ◽

Cited By ~ 1

Author(s):

David A. Kolin ◽

Scott Kulm ◽

Olivier Elemento

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

High Risk ◽

Genetic Risk ◽

Genetic Factors ◽

Hazard Ratio ◽

Low Risk ◽

Clinical Risk Factors ◽

Clinical Risk ◽

Increased Risk

BACKGROUNDBoth clinical and genetic factors drive the risk of venous thromboembolism. However, whether clinically recorded risk factors and genetic variants can be combined into a clinically applicable predictive score remains unknown.METHODSUsing Cox proportional-hazard models, we analyzed the association of risk factors with the likelihood of venous thromboembolism in U.K. Biobank, a large prospective cohort. We created a novel ten point clinical score using seven established clinical risk factors for venous thromboembolism. We also generated a polygenic risk score of 21 single nucleotide polymorphisms to quantify genetic risk. The genetic score was categorized into high risk (top two deciles of scores), intermediate risk (deciles three to eight), and low risk (lowest two deciles). The discrete clinical score led to the following approximate decile categorizations: high risk (5 to 10 points), intermediate risk (3 to 4 points), and low risk (0 to 2 points).RESULTSAmongst the 502,536 participants in the U.K. Biobank, there were 4,843 events of venous thromboembolism. Analyses of established clinical risk factors and the most commonly used medications revealed that participants were at decreased risk of venous thromboembolism if they had ever used oral contraceptive pills (hazard ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.99) or if they currently used bendroflumethiazide (hazard ratio, 0.84; 95% CI, 0.74 to 0.95), cod liver oil capsules (hazard ratio, 0.87; 95% CI, 0.77 to 0.99), or atenolol (hazard ratio, 0.79; 95% CI, 0.68 to 0.91). Participants were at significantly increased risk of venous thromboembolism if they were at high clinical risk (hazard ratio, 5.98; 95% CI, 5.43 to 6.59) or high genetic risk (hazard ratio, 2.28; 95% CI, 2.07 to 2.51) relative to participants at low clinical or genetic risk, respectively. Combining clinical risk factors with genetic risk factors produced a model that better predicted risk of venous thromboembolism than either model alone (P<0.001). Participants at high clinical and genetic risk in the combined score had over an eightfold increased risk of venous thromboembolism relative to participants at low risk (hazard ratio, 8.27; 95% CI 7.59 to 9.00).CONCLUSIONSBy assessing venous thromboembolic events in over 500,000 participants, we identified several known and novel associations between risk factors and venous thromboembolism. Participants in the high risk group of a combined score, consisting of clinical and genetic factors, were over eight times more likely to experience venous thromboembolism than participants in the low risk group.

Download Full-text

Impact of obesity on the evolution of outcomes in peritoneal dialysis patients

Clinical Kidney Journal ◽

10.1093/ckj/sfaa055 ◽

2020 ◽

Author(s):

Maria Quero ◽

Jordi Comas ◽

Emma Arcos ◽

Miguel Hueso ◽

Diego Sandoval ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Univariate Analysis ◽

Normal Weight ◽

Hazard Ratio ◽

Obese Patients ◽

Weight Changes ◽

Technique Survival ◽

Undergo Kidney Transplantation ◽

Using Data ◽

The Impact

Abstract Background Some studies reveal that obesity is associated with a decrease in mortality in haemodialysis (HD) patients. However, few studies have addressed the association between body mass index (BMI) and peritoneal dialysis (PD) patients. Methods We performed this longitudinal, retrospective study to evaluate the impact of obesity on PD patients, using data from the Catalan Registry of Renal Patients from 2002 to 2015 (n = 1573). Obesity was defined as BMI ≥30; low weight: BMI <18.5; normal range: BMI = 18.5–24.99; and pre-obesity: BMI = 25–29.99 kg/m2. Variations in BMI were calculated during follow-up. The main outcomes evaluated were the technique and patient survival. Results Obesity was observed in 20% of patients starting PD. We did not find differences in sex or PD modality, with the obesity group being older (65.9% are ≥55 years versus 59% non-obese, P = 0.003) and presenting more diabetes mellitus and cardiovascular disease (CVD) (47.9% obese versus 25.1% non-obese and 41.7% versus 31.5%, respectively). We did not observe differences in haemoglobin, albumin and Kt/V in obese patients. Regarding peritonitis rate, we did not find any difference between groups, presenting more peritonitis patients on continuous ambulatory peritoneal dialysis and aged ≥65 years [sub-hazard ratio (SHR) = 1.75, P = 0.000 and SHR = 1.56, P = 0.009]. In relation to technique survival, we found higher transfer to HD in the obese group of patients in the univariate analysis, which was not confirmed in the multivariate analysis (SHR = 1.12, P = 0.4), and we did not find differences in mortality rate. In relation to being transplanted, the underweight group, elderly and patients with CVD or diabetic nephropathy presented less probability to undergo kidney transplantation (SHR = 0.65, 0.24, 0.5 and 0.54, P < 0.05). Obese patients did not present differences in survival with weight changes but in normal-weight patients, a gain of 7% of the basal weight during the first year had a protective effect on death risk (hazard ratio 0.6, P = 0.034). Conclusions Obese and non-obese patients starting on PD had similar outcomes.

Download Full-text

Additive Effect of Periodontal Disease and Obesity on COVID-19 Outcomes

Journal of Dental Research ◽

10.1177/00220345211029638 ◽

2021 ◽

pp. 002203452110296

Author(s):

H. Larvin ◽

S. Wilmott ◽

J. Kang ◽

V.R. Aggarwal ◽

S. Pavitt ◽

...

Keyword(s):

Oral Health ◽

Periodontal Disease ◽

Hospital Admission ◽

Odds Ratio ◽

Admission Rate ◽

Mortality Rates ◽

Normal Weight ◽

Hazard Ratio ◽

Hospital Admission Rate ◽

The Impact

This study aims to examine the impact of periodontal disease in obesity on COVID-19 infection and associated outcomes. This retrospective longitudinal study included 58,897 UK Biobank participants tested for COVID-19 between March 2020 and February 2021. Self-reported oral health indicators (bleeding gums, painful gums, and loose teeth) were used as surrogates for periodontal disease. Body fat levels were quantified by body mass index (BMI) and categorized as normal weight (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2), and obese (≥30 kg/m2). Multivariable logistic regression and Cox proportional hazard models were used to quantify risk of COVID-19 infection, hospital admission, and mortality, adjusted for participants’ demographics and covariates. Of 58,897 participants, 14,466 (24.6%) tested positive for COVID-19 infection. COVID-19 infection was higher for participants who were overweight (odds ratio, 1.18; 95% CI, 1.12 to 1.24) and obese (odds ratio, 1.33; 95% CI, 1.26 to 1.41) as compared with those of normal weight, but infection was not affected by periodontal disease. The hospital admission rate was 57% higher (hazard ratio, 1.57; 95% CI, 1.25 to 1.97) in the obese group with periodontal disease than without periodontal disease, and admission rates increased with BMI category (normal weight, 4.4%; overweight, 6.8%; obese, 10.1%). Mortality rates also increased with BMI category (normal weight, 1.9%; overweight, 3.17%; obese, 4.5%). In addition, for participants with obesity, the mortality rate was much higher (hazard ratio, 3.11; 95% CI, 1.91 to 5.06) in participants with periodontal disease than those without. Obesity is associated with higher hospitalization and mortality rates, and periodontal disease may exacerbate this impact. The results could inform health providers, policy makers, and the general public of the importance to maintain good oral health through seamless provision of dental services and public oral health prevention initiatives.

Download Full-text

Polygenic risk score, healthy lifestyles, and risk of incident depression

Translational Psychiatry ◽

10.1038/s41398-021-01306-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhi Cao ◽

Hongxi Yang ◽

Yixuan Ye ◽

Yuan Zhang ◽

Shu Li ◽

...

Keyword(s):

Risk Score ◽

Genetic Risk ◽

Lifestyle Factors ◽

Polygenic Risk Score ◽

Healthy Lifestyles ◽

Current Smoking ◽

Polygenic Risk ◽

High Genetic Risk ◽

Moderate Alcohol Intake ◽

The Uk

AbstractGenetic factors increase the risk of depression, but the extent to which this can be offset by modifiable lifestyle factors is unknown. We investigated whether a combination of healthy lifestyles is associated with lower risk of depression regardless of genetic risk. Data were obtained from the UK Biobank and consisted of 339,767 participants (37–73 years old) without depression between 2006 and 2010. Genetic risk was categorized as low, intermediate, or high according to polygenic risk score for depression. A combination of healthy lifestyles factors—including no current smoking, regular physical activity, a healthy diet, moderate alcohol intake and a body mass index <30 kg/m2—was categorized into favorable, intermediate, and unfavorable lifestyles. The risk of depression was 22% higher among those at high genetic risk compared with those at low genetic risk (HR = 1.22, 95% CI: 1.14–1.30). Participants with high genetic risk and unfavorable lifestyle had a more than two-fold risk of incident depression compared with low genetic risk and favorable lifestyle (HR = 2.18, 95% CI: 1.84–2.58). There was no significant interaction between genetic risk and lifestyle factors (P for interaction = 0.69). Among participants at high genetic risk, a favorable lifestyle was associated with nearly 50% lower relative risk of depression than an unfavorable lifestyle (HR = 0.51, 95% CI: 0.43–0.60). We concluded that genetic and lifestyle factors were independently associated with risk of incident depression. Adherence to healthy lifestyles may lower the risk of depression regardless of genetic risk.

Download Full-text

Genetic risk, adherence to a healthy lifestyle, and type 2 diabetes risk among 550,000 Chinese adults: results from 2 independent Asian cohorts

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz310 ◽

2020 ◽

Vol 111 (3) ◽

pp. 698-707 ◽

Cited By ~ 2

Author(s):

Haoxin Li ◽

Chiea-Chuen Khor ◽

Junning Fan ◽

Jun Lv ◽

Canqing Yu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Risk ◽

Lower Risk ◽

Healthy Lifestyle ◽

Genetic Risk Score ◽

Lifestyle Factors ◽

Diabetes Risk ◽

Unhealthy Lifestyle ◽

High Genetic Risk

ABSTRACT Background Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown. Objectives The aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes. Methods We defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes. Results In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle. Conclusions In 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.

Download Full-text

Risk of venous thromboembolism following surgical treatment of superficial venous incompetence

VASA ◽

10.1024/0301-1526/a000656 ◽

2017 ◽

Vol 46 (6) ◽

pp. 484-489 ◽

Cited By ~ 7

Author(s):

Tom Barker ◽

Felicity Evison ◽

Ruth Benson ◽

Alok Tiwari

Keyword(s):

Venous Thromboembolism ◽

Varicose Vein ◽

Lower Incidence ◽

Varicose Veins ◽

Secondary Data ◽

Foam Sclerotherapy ◽

Increased Risk ◽

Significant Difference ◽

Chi Squared ◽

One Year

Abstract. Background: The invasive management of varicose veins has a known risk of post-operative deep venous thrombosis and subsequent pulmonary embolism. The aim of this study was to evaluate absolute and relative risk of venous thromboembolism (VTE) following commonly used varicose vein procedures. Patients and methods: A retrospective analysis of secondary data using Hospital Episode Statistics database was performed for all varicose vein procedures performed between 2003 and 2013 and all readmissions for VTE in the same patients within 30 days, 90 days, and one year. Comparison of the incidence of VTEs between procedures was performed using a Pearson’s Chi-squared test. Results: In total, 261,169 varicose vein procedures were performed during the period studied. There were 686 VTEs recorded at 30 days (0.26 % incidence), 884 at 90 days (0.34 % incidence), and 1,246 at one year (0.48 % incidence). The VTE incidence for different procedures was between 0.15–0.35 % at 30 days, 0.26–0.50 % at 90 days, and 0.46–0.58 % at one year. At 30 days there was a significantly lower incidence of VTEs for foam sclerotherapy compared to other procedures (p = 0.01). There was no difference in VTE incidence between procedures at 90 days (p = 0.13) or one year (p = 0.16). Conclusions: Patients undergoing varicose vein procedures have a small but appreciable increased risk of VTE compared to the general population, with the effect persisting at one year. Foam sclerotherapy had a lower incidence of VTE compared to other procedures at 30 days, but this effect did not persist at 90 days or at one year. There was no other significant difference in the incidence of VTE between open, endovenous, and foam sclerotherapy treatments.

Download Full-text

Heterozygosity for the alpha1-antitrypsin Z allele confers high genetic risk of cholangiocarcinoma

Zeitschrift für Gastroenterologie ◽

10.1055/s-0030-1263803 ◽

2010 ◽

Vol 48 (08) ◽

Author(s):

V Zimmer ◽

F Mihalache ◽

A Höblinger ◽

F Grünhage ◽

M Krawczyk ◽

...

Keyword(s):

Genetic Risk ◽

High Genetic Risk ◽

Alpha1 Antitrypsin

Download Full-text

Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

Public Health Nutrition ◽

10.1017/s1368980021001592 ◽

2021 ◽

pp. 1-25

Author(s):

Qionggui Zhou ◽

Xuejiao Liu ◽

Yang Zhao ◽

Pei Qin ◽

Yongcheng Ren ◽

...

Keyword(s):

Cohort Study ◽

Population Based ◽

Normal Weight ◽

Sensitivity Analyses ◽

Hypertension Status ◽

Moderation Effect ◽

Increased Risk ◽

All Cause Mortality ◽

Chinese Cohort ◽

The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Download Full-text