Cardiovascular risk according to genetic predisposition to gout, lifestyle and metabolic health across prospective European and Korean cohorts.

OBJECTIVE: Recent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries. METHODS: A total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS). RESULTS: Individuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits. CONCLUSIONS: Our findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies.

All-cause and cause-specific mortality risks in individuals with diabetes living alone: A large-scale population-based cohort study.

AIMS: The rise in one-person households is a global trend. We aimed to investigate mortality risk in individuals with diabetes living alone (IDLA) using a large-scale population-based database. METHODS: A total of 2,447,557 adults with type 2 diabetes were identified from the Korean National Health Information Database. One-person households were defined based on the number of registered family members. The risks of all-cause and cause-specific mortalities were estimated using a multivariable Cox proportional hazards regression model. RESULTS: During a median follow-up period of 6.0 years, 191,084 deaths (7.8 %) occurred. IDLA had a higher risk of mortality compared to those not living alone after adjusting for potential confounders (HR 1.20, 95 % CI: 1.18-1.22). This association was more prominent in younger individuals, men, and those with low income, and it was dependent on the duration of living alone. The risks of cause-specific mortality were all significantly higher in the IDLA group compared with the non-IDLA group. Adherence to favorable lifestyle behaviors was associated with a significant reduction in all-cause mortality, particularly in IDLA. CONCLUSIONS: The elevated risk of mortality in IDLA highlights the need for tailored medical interventions and social assistance, particularly for those with unhealthy lifestyles or low income.

Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients.

Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.

Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review.

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

The Impact of Lifestyle on Cardiovascular Risk in Patients with Gout: a Population-based Cohort Study.

AIMS: Gout is associated with a significant burden of cardiovascular disease. The aim of this study was to evaluate the impact of a favorable lifestyle on incident cardiovascular events in patients with gout. METHODS: We identified 9 110 patients with gout from the UK Biobank cohort based on self-report and/or hospital diagnostic codes. Lifestyle behaviors, including smoking status, physical activity, obesity, and diet, were categorized into three patterns: favorable (3-4 healthy factors), intermediate (2 healthy factors), and unfavorable (0-1 healthy factor). The cardiovascular risk of participants with and without gout was estimated based on their serum uric acid levels and lifestyle patterns. RESULTS: Among 9 110 patients with gout and 457 596 participants without gout, the median follow-up duration was 8.9 years. The incidence rate of cardiovascular disease was significantly higher in the gout population than in the non-gout population (11.38 vs 5.49 per 1000 person-years). The gout population consistently exhibited a high cardiovascular risk, irrespective of uric acid levels, whereas a positive correlation was observed between uric acid levels and cardiovascular risk in the non-gout population. Adopting a favorable lifestyle pattern was associated with a lower risk of cardiovascular disease in both gout and non-gout populations. Across all categories of uric acid, a favorable lifestyle was found to reduce cardiovascular risk in patients with gout. CONCLUSION: Patients with gout remain at high risk of developing cardiovascular disease despite having normal uric acid levels. Lifestyle modifications may represent an effective and cost-efficient therapeutic approach for preventing cardiovascular events in this population.

Polygenic risk score-based phenome-wide association for glaucoma and its impact on disease susceptibility in two large biobanks.

BACKGROUND: Glaucoma is a leading cause of worldwide irreversible blindness. Considerable uncertainty remains regarding the association between a variety of phenotypes and the genetic risk of glaucoma, as well as the impact they exert on the glaucoma development. METHODS: We investigated the associations of genetic liability for primary open angle glaucoma (POAG) with a wide range of potential risk factors and to assess its impact on the risk of incident glaucoma. The phenome-wide association study (PheWAS) approach was applied to determine the association of POAG polygenic risk score (PRS) with a wide range of phenotypes in 377, 852 participants from the UK Biobank study and 43,623 participants from the Penn Medicine Biobank study, all of European ancestry. Participants were stratified into four risk tiers: low, intermediate, high, and very high-risk. Cox proportional hazard models assessed the relationship of POAG PRS and ocular factors with new glaucoma events. RESULTS: In both discovery and replication set in the PheWAS, a higher genetic predisposition to POAG was specifically correlated with ocular disease phenotypes. The POAG PRS exhibited correlations with low corneal hysteresis, refractive error, and ocular hypertension, demonstrating a strong association with the onset of glaucoma. Individuals carrying a high genetic burden exhibited a 9.20-fold, 11.88-fold, and 28.85-fold increase in glaucoma incidence when associated with low corneal hysteresis, high myopia, and elevated intraocular pressure, respectively. CONCLUSION: Genetic susceptibility to POAG primarily influences ocular conditions, with limited systemic associations. Notably, the baseline polygenic risk for POAG robustly associates with new glaucoma events, revealing a large combined effect of genetic and ocular risk factors on glaucoma incidents.

Association between genetic risk and adherence to healthy lifestyle for developing age-related hearing loss.

BACKGROUND: Previous studies have shown that lifestyle/environmental factors could accelerate the development of age-related hearing loss (ARHL). However, there has not yet been a study investigating the joint association among genetics, lifestyle/environmental factors, and adherence to healthy lifestyle for risk of ARHL. We aimed to assess the association between ARHL genetic variants, lifestyle/environmental factors, and adherence to healthy lifestyle as pertains to risk of ARHL. METHODS: This case-control study included 376,464 European individuals aged 40 to 69 years, enrolled between 2006 and 2010 in the UK Biobank (UKBB). As a replication set, we also included a total of 26,523 individuals considered of European ancestry and 9834 individuals considered of African-American ancestry through the Penn Medicine Biobank (PMBB). The polygenic risk score (PRS) for ARHL was derived from a sensorineural hearing loss genome-wide association study from the FinnGen Consortium and categorized as low, intermediate, high, and very high. We selected lifestyle/environmental factors that have been previously studied in association with hearing loss. A composite healthy lifestyle score was determined using seven selected lifestyle behaviors and one environmental factor. RESULTS: Of the 376,464 participants, 87,066 (23.1%) cases belonged to the ARHL group, and 289,398 (76.9%) individuals comprised the control group in the UKBB. A very high PRS for ARHL had a 49% higher risk of ARHL than those with low PRS (adjusted OR, 1.49; 95% CI, 1.36-1.62; P < .001), which was replicated in the PMBB cohort. A very poor lifestyle was also associated with risk of ARHL (adjusted OR, 3.03; 95% CI, 2.75-3.35; P < .001). These risk factors showed joint effects with the risk of ARHL. Conversely, adherence to healthy lifestyle in relation to hearing mostly attenuated the risk of ARHL even in individuals with very high PRS (adjusted OR, 0.21; 95% CI, 0.09-0.52; P < .001). CONCLUSIONS: Our findings of this study demonstrated a significant joint association between genetic and lifestyle factors regarding ARHL. In addition, our analysis suggested that lifestyle adherence in individuals with high genetic risk could reduce the risk of ARHL.

Effectiveness of a Social Networking Site Based Automatic Mobile Message Providing System on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

BACKGRUOUND: This study investigated the effectiveness of a social networking site (SNS)-based automatic mobile message providing system on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-month, randomized, open-label, controlled, parallel-group trial was conducted. One hundred and ten participants with T2DM were randomized to a mobile message system (MMS) (n=55) or control group (n=55). The MMS group received protocolbased automated messages two times per day for 10 weeks regarding diabetes self-management through KakaoTalk SNS messenger. The primary outcome was the difference in the change in glycated hemoglobin (HbA1c) levels (%) from baseline to week 12. RESULTS: HbA1c levels were more markedly decreased in the MMS group (8.4%±0.7% to 8.0%±1.1%) than in the control group (8.5%±0.8% to 8.4%±0.8%), resulting in a significant between-group difference (P=0.027). No differences were observed in changes in fasting glucose levels, lipid profiles, and the number of participants who experienced hypoglycemia, or in changes in lifestyle behavior between groups. However, the self-monitoring of blood glucose frequency was significantly increased in the MMS group compared to the control group (P=0.003). In addition, sleep duration was increased in the MMS group, but was not changed in the control group. CONCLUSION: An SNS-based automatic mobile message providing system was effective in improving glycemic control in patients in T2DM. Studies which based on a more individualized protocol, and investigate longer beneficial effect and sustainability will be required in the future.

Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

BACKGRUOUND: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. METHODS: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. RESULTS: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. CONCLUSION: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Fracture Risk in Middle-Aged and Older Patients With Inflammatory Bowel Disease: A Korean Nationwide Population-Based Cohort Study.

BACKGROUND: Fracture risks and associated factors are poorly understood in middle-aged and older Asian populations with inflammatory bowel disease (IBD). Therefore, we investigated fracture risk and the effects of comorbidities and lifestyle habits on the risk of developing fractures in middle-aged and older Korean patients with IBD. METHODS: We conducted a nationwide population-based cohort study using data from the National Health Insurance Corporation Database. Patients with IBD who underwent the National Screening Program and were over 40 years of age were included in the study. We compared patients with age- and sex-matched controls. The incidence of fractures, including vertebral, hip, and other sites, was determined using claims data. RESULTS: The risk of total fractures and vertebral fractures was significantly higher in the IBD group (adjusted hazard ratio [HR], 1.31, 95% confidence interval [CI], 1.16-1.48; adjusted HR, 1.59, 95% CI, 1.33-1.92, respectively). Obesity, diabetes, hypertension, and lack of exercise were associated with increased fracture risk in patients with ulcerative colitis (UC). In contrast, the risk increases in patients with Crohn's disease regardless of comorbidities and lifestyle preferences. CONCLUSION: The risk of bone fracture, especially vertebral fracture, is high in middle-aged and older Korean patients with IBD. Obesity, diabetes, hypertension, and lack of exercise are all risk factors associated with bone fractures in patients with UC. These findings are helpful for clinicians to educate patients with IBD on bone health and raise awareness of bone fractures in patients with UC who have specific risk factors.

The impact of diabetes status on total and site-specific cancer risk in the elderly population: A nationwide cohort study.

AIMS: We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. METHODS: This study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. RESULTS: The risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65-74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. CONCLUSIONS: Diabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.

Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020.

BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

Associations of polyneuropathy with risk of all-cause and cardiovascular mortality, cardiovascular disease events stratified by diabetes status.

AIMS/INTRODUCTION: We investigated the association of polyneuropathy (PN) with all-cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status. MATERIALS AND METHODS: This prospective cohort study used the UK Biobank. Polyneuropathy was defined based on nurse-led interviews or ICD codes for polyneuropathy. Cox proportional hazards models were used to investigate the association of polyneuropathy with clinical outcomes. RESULTS: A total of 459,127 participants were included in the analysis. Polyneuropathy was significantly associated with all-cause and cardiovascular mortality, and with CVD events even after adjusting for CVD risk factors across all diabetes statuses. Metabolic parameters HbA1c , waist circumference, BMI and the inflammatory parameter C-reactive protein showed significant mediation effects for the association between polyneuropathy and CVD. Adherence to a favorable lifestyle was associated with a lower risk of all-cause and cardiovascular mortality regardless of polyneuropathy status. CONCLUSIONS: Polyneuropathy was associated with all-cause and cardiovascular mortality, and with CVD events in subjects with diabetes or prediabetes, even those having normal glucose tolerance. This study suggests the importance of polyneuropathy as a risk factor for death and highlights the necessity of early diagnosis and lifestyle intervention for those with type 2 diabetes and polyneuropathy.

Impacts of gender and lifestyle on the association between depressive symptoms and cardiovascular disease risk in the UK Biobank.

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40-69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24-1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48-0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58-0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62-0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68-0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71-0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk.

Development of complemented comprehensive networks for rapid screening of repurposable drugs applicable to new emerging disease outbreaks.

BACKGROUND: Computational drug repurposing is crucial for identifying candidate therapeutic medications to address the urgent need for developing treatments for newly emerging infectious diseases. The recent COVID-19 pandemic has taught us the importance of rapidly discovering candidate drugs and providing them to medical and pharmaceutical experts for further investigation. Network-based approaches can provide repurposable drugs quickly by leveraging comprehensive relationships among biological components. However, in a case of newly emerging disease, applying a repurposing methods with only pre-existing knowledge networks may prove inadequate due to the insufficiency of information flow caused by the novel nature of the disease. METHODS: We proposed a network-based complementary linkage method for drug repurposing to solve the lack of incoming new disease-specific information in knowledge networks. We simulate our method under the controlled repurposing scenario that we faced in the early stage of the COVID-19 pandemic. First, the disease-gene-drug multi-layered network was constructed as the backbone network by fusing comprehensive knowledge database. Then, complementary information for COVID-19, containing data on 18 comorbid diseases and 17 relevant proteins, was collected from publications or preprint servers as of May 2020. We estimated connections between the novel COVID-19 node and the backbone network to construct a complemented network. Network-based drug scoring for COVID-19 was performed by applying graph-based semi-supervised learning, and the resulting scores were used to validate prioritized drugs for population-scale electronic health records-based medication analyses. RESULTS: The backbone networks consisted of 591 diseases, 26,681 proteins, and 2,173 drug nodes based on pre-pandemic knowledge. After incorporating the 35 entities comprised of complemented information into the backbone network, drug scoring screened top 30 potential repurposable drugs for COVID-19. The prioritized drugs were subsequently analyzed in electronic health records obtained from patients in the Penn Medicine COVID-19 Registry as of October 2021 and 8 of these were found to be statistically associated with a COVID-19 phenotype. CONCLUSION: We found that 8 of the 30 drugs identified by graph-based scoring on complemented networks as potential candidates for COVID-19 repurposing were additionally supported by real-world patient data in follow-up analyses. These results show that our network-based complementary linkage method and drug scoring algorithm are promising strategies for identifying candidate repurposable drugs when new emerging disease outbreaks.

Genome-wide polygenic risk scores for hypertensive disease during pregnancy can also predict the risk for long-term cardiovascular disease.

BACKGROUND: Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. OBJECTIVE: This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. STUDY DESIGN: Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. RESULTS: Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. CONCLUSION: High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.

Association of glaucoma and lifestyle with incident cardiovascular disease: a longitudinal prospective study from UK Biobank.

The shared pathophysiological features of the cerebrovascular disease (CVD) and glaucoma suggest an association between the two diseases. Using the prospective UK Biobank cohort, we examined the associations between glaucoma and incident CVD and assessed the extent to which a healthy lifestyle reduced the CVD risk in subjects with glaucoma, using a scoring system consisting of four factors: current smoking, obesity, regular physical activity, and a healthy diet. During a mean follow-up time of 8.9 years, 22,649 (4.9%) incident CVD cases were documented. Multivariable Cox regression analyses revealed that subjects with glaucoma were significantly more likely to exhibit incident CVD (hazard ratio [HR]:1.19, 95% confidence interval [CI] 1.03-1.37; p = 0.016) than controls. In the further subgroup analyses, glaucoma increased incident CVD risk both in the young (40-55 years) and the old (56-70 years) and in both sexes, with higher risk in the young (HR: 1.33, CI 1.02-1.74) and female subjects (HR: 1.32, CI 1.14-1.52). When we analyze the associations between glaucoma and incident CVD by lifestyle factors, the highest absolute risks were observed in individuals with both glaucoma and an unhealthy lifestyle (HR: 2.66, CI 2.22-3.19). In conclusion, glaucoma was an independent risk factor for incident CVD. A healthy lifestyle was associated with a substantially lower risk for CVD incidence among adults with glaucoma.

Discovering comorbid diseases using an inter-disease interactivity network based on biobank-scale PheWAS data.

MOTIVATION: Understanding comorbidity is essential for disease prevention, treatment and prognosis. In particular, insight into which pairs of diseases are likely or unlikely to co-occur may help elucidate the potential relationships between complex diseases. Here, we introduce the use of an inter-disease interactivity network to discover/prioritize comorbidities. Specifically, we determine disease associations by accounting for the direction of effects of genetic components shared between diseases, and categorize those associations as synergistic or antagonistic. We further develop a comorbidity scoring algorithm to predict whether diseases are more or less likely to co-occur in the presence of a given index disease. This algorithm can handle networks that incorporate relationships with opposite signs. RESULTS: We finally investigate inter-disease associations among 427 phenotypes in UK Biobank PheWAS data and predict the priority of comorbid diseases. The predicted comorbidities were verified using the UK Biobank inpatient electronic health records. Our findings demonstrate that considering the interaction of phenotype associations might be helpful in better predicting comorbidity. AVAILABILITY AND IMPLEMENTATION: The source code and data of this study are available at https://github.com/dokyoonkimlab/DiseaseInteractiveNetwork. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study.

BACKGROUND: Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. METHODS: Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. RESULTS: After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18-1.55)], including coronary artery disease [aHR 1.31 (1.08-1.59)], myocardial infarction [aHR 1.65 (1.27-2.15)], ischemic stroke [aHR 1.68 (1.18-2.39)], peripheral artery disease [aHR 1.69 (1.14-2.51)], heart failure [aHR 1.41 (1.06-1.87)], mitral regurgitation [aHR 2.25 (1.51-3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18-1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. CONCLUSIONS: GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.