Women With Diabetes Are at Increased Relative Risk of Heart Failure Compared to Men: Insights From UK Biobank

Aims: To investigate the effect of diabetes on mortality and incident heart failure (HF) according to sex, in the low risk population of UK Biobank. To evaluate potential contributing factors for any differences seen in HF end-point.Methods: The entire UK Biobank study population were included. Participants that withdrew consent or were diagnosed with diabetes after enrolment were excluded from the study. Univariate and multivariate cox regression models were used to assess endpoints of mortality and incident HF, with median follow-up periods of 9 years and 8 years respectively.Results: A total of 493,167 participants were included, hereof 22,685 with diabetes (4.6%). Two thousand four hundred fifty four died and 1,223 were diagnosed or admitted with HF during the follow up periods of 9 and 8 years respectively. Overall, the mortality and HF risk were almost doubled in those with diabetes compared to those without diabetes (hazard ratio (HR) of 1.9 for both mortality and heart failure) in the UK Biobank population. Women with diabetes (both types) experience a 22% increased risk of HF compared to men (HR of 2.2 (95% CI: 1.9–2.5) vs. 1.8 (1.7–2.0) respectively). Women with type 1 diabetes (T1DM) were associated with 88% increased risk of HF compared to men (HR 4.7 (3.6–6.2) vs. 2.5 (2.0–3.0) respectively), while the risk of HF for type 2 diabetes (T2DM) was 17% higher in women compared to men (2.0 (1.7–2.3) vs. 1.7 (1.6–1.9) respectively). The increased risk of HF in women was independent of confounding factors. The findings were similar in a model with all-cause mortality as a competing risk. This interaction between sex, diabetes and outcome of HF is much more prominent for T1DM (p = 0.0001) than T2DM (p = 0.1).Conclusion: Women with diabetes, particularly those with T1DM, experience a greater increase in risk of heart failure compared to men with diabetes, which cannot be explained by the increased prevalence of cardiac risk factors in this cohort.

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Fitness, Fatness, and Mortality in Men and Women From the UK Biobank: Prospective Cohort Study

Journal of the American Heart Association ◽

10.1161/jaha.120.019605 ◽

2021 ◽

Author(s):

Jakob Tarp ◽

Anders Grøntved ◽

Miguel A. Sanchez‐Lastra ◽

Knut Eirik Dalene ◽

Ding Ding ◽

...

Keyword(s):

Body Composition ◽

Cardiorespiratory Fitness ◽

Cox Regression ◽

World Health ◽

Uk Biobank ◽

Men And Women ◽

Increased Risk ◽

All Cause Mortality ◽

The Uk

Background Cardiorespiratory fitness may moderate the association between obesity and all‐cause mortality (ie, the “fat‐but‐fit” hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness‐fatness combinations. We also formed fitness‐fatness combinations based on bioimpedance as a direct measure of body composition. All‐cause mortality was ascertained from death registries. Multivariable‐adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness‐fatness combinations and all‐cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow‐up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight–fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow‐up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17–2.71) times higher in unfit‐obese men but not higher in obese‐fit men (0.94 [95% CI, 0.60–1.48]). In contrast, there was no increased risk in obese‐unfit women (1.09 [95% CI, 0.44–1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.

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Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319508 ◽

2021 ◽

pp. bjophthalmol-2021-319508

Author(s):

Xianwen Shang ◽

Zhuoting Zhu ◽

Yu Huang ◽

Xueli Zhang ◽

Wei Wang ◽

...

Keyword(s):

Heart Disease ◽

Age Related Macular Degeneration ◽

Hospital Inpatient ◽

Uk Biobank ◽

Age Related ◽

Incident Dementia ◽

Increased Risk ◽

The Uk ◽

Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

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Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa638 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4688-e4698

Author(s):

Zhi Cao ◽

Chenjie Xu ◽

Hongxi Yang ◽

Shu Li ◽

Fusheng Xu ◽

...

Keyword(s):

Body Mass Index ◽

Cohort Study ◽

Lower Risk ◽

Serum Urate ◽

Healthy Weight ◽

Uk Biobank ◽

Health Records ◽

Increased Risk ◽

The Uk

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

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Left atrial coupling index versus left atrial function index in heart failure with reduced ejection fraction and iron deficiency

European Heart Journal ◽

10.1093/eurheartj/ehab724.0887 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Tsarouchas ◽

C Bakogiannis ◽

D Mouselimis ◽

E.D Pagourelias ◽

I Kelemanis ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Left Atrial ◽

Cox Regression ◽

Relevant Literature ◽

Reduced Ejection Fraction ◽

Function Index ◽

Coupling Index ◽

Increased Risk

Abstract Background Left atrial (LA) form and function has been the focus of extensive research in heart failure with reduced ejection fraction (HFrEF). The LA coupling index (LACI, see Picture 1 for definition) and the LA function Index (LAFI) have both been proposed as potent predictors of morbidity and mortality in HFrEF. Albeit promising, both parameters have drawbacks that could limit their usefulness in clinical settings - LACI can only be measured during sinus rhythm (SR), while LAFI calculation is arguably more involved. A side-by-side comparison of the two indices has not yet been performed. Purpose Investigate and compare the feasibility and efficacy of using LACI and LAFI as prognostic factors in HFrEF. Methods HFrEF patients that visited our outpatient HF clinic were invited to participate in the study. Clinical examination, 6-minute walk testing, and a full echocardiographic study were performed, the latter enabling quantification of LACI, LAFI, as well as most traditional echocardiographic predictors of HF prognosis (Picture 1). LACI and LAFI cut-offs of 6 and 25 respectively were defined in accordance with the relevant literature. Cox regression was performed to assess each parameter's correlation with risk of HF-related hospitalization and mortality over a 6-month follow-up period. Results In the end, 63 patients were included in the study (aged 69.3±9.7 years, 84% male). LACI could not be measured in 19 patients due to atrial tachycardia. The median LACI was 6.2 (8.7) while the median LAFI of the entire sample was 24.8 (44.5). LACI and LAFI correlated strongly (r=−0.813, p<0.001). Neither correlated significantly with the risk of HF-related hospitalization (Picture 1) or death in our sample (Picture 2). 6MWD was the only parameter to independently correlate with increased risk of hospitalization (HR=0.39, p<0.001) or death (HR=0.42, p=0.02). Conclusions The collinearity detected between LACI and LAFI indicate that both quantify similar aspects of left atrial (dys)function. That said, neither index had significant capability to predict hospitalization or death in our sample of HFrEF patients. Although a non-significant trend for higher LACI in patients with poorer prognosis was detected in our sample, it was also incalculable in 30% of patients, who were not in SR during echocardiography. Extended follow-up of an expanded sample size will enable more refined investigation of LACI's and LAFI's prognostic capacity. FUNDunding Acknowledgement Type of funding sources: None. Hospitalization Cox regression results LACI and LAFI survival curves

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Association of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry

Scientific Reports ◽

10.1038/s41598-021-91113-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Margaret M. Parker ◽

Scott M. Damrauer ◽

Catherine Tcheandjieu ◽

David Erbe ◽

Emre Aldinc ◽

...

Keyword(s):

Heart Failure ◽

Odds Ratio ◽

African Ancestry ◽

Significant Proportion ◽

The United States ◽

Uk Biobank ◽

Diagnosis Codes ◽

Increased Risk ◽

Tunnel Syndrome ◽

The Uk

AbstractHereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3–4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6–15.6, p = 4.2 × 10−5), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2–2.4, p = 6.0 × 10–3) and Million Veteran Program (OR = 1.5, 95% CI 1.2–1.8, p = 1.8 × 10−4). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7–4.5, p = 2.6 × 10−5) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment.

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Association of the Transthyretin Variant V122I With Polyneuropathy Among Individuals of African Descent

10.1101/2020.11.10.20219675 ◽

2020 ◽

Author(s):

Margaret M. Parker ◽

Scott M. Damrauer ◽

Catherine Tcheandjieu ◽

David Erbe ◽

Emre Aldinc ◽

...

Keyword(s):

Cox Regression ◽

African Descent ◽

Gene Mutations ◽

Uk Biobank ◽

Cardiac Phenotype ◽

Diagnosis Codes ◽

Increased Risk ◽

Tunnel Syndrome ◽

The Common ◽

The Uk

BACKGROUNDHereditary transthyretin-mediated (hATTR) amyloidosis is a progressively debilitating disease caused by transthyretin (TTR) gene mutations. The V122I variant, a common pathogenic TTR mutation found primarily in individuals of West African descent, is frequently associated with cardiomyopathy.METHODSThe association between the V122I variant and ICD10 diagnosis codes was assessed in the UK Biobank black subpopulation (N=6062); whether significant associations could be replicated in the Penn Medicine Biobank (N=5737) and Million Veteran Program (N=82,382) was then investigated. Cumulative incidence of common hATTR amyloidosis manifestations (polyneuropathy, carpal tunnel syndrome, cardiomyopathy, and heart failure) was estimated by V122I genotype in the UK Biobank using Cox regression controlling for age, sex, and genetic ancestry.RESULTSPhenome-wide analysis identified a significant association between V122I genotype and polyneuropathy diagnosis (odds ratio [OR]=6.4, 95% confidence interval [CI]=2.6–15.6, P=4.2×10−5) in the UK Biobank. A significant association was also observed in the Penn Medicine Biobank (OR=1.6, 95% CI=1.2–2.4, P=6.0×10−3) and the Million Veteran Program (OR=1.5, 95% CI=1.2–1.8, P=1.8×10−4). Prevalence of a polyneuropathy diagnosis among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. In the UK Biobank, common hATTR amyloidosis manifestations were significantly enriched in V122I carriers compared with non-carriers (HR=2.8; 95% CI=1.7–4.5; P=2.6×10−5). By age 75, 37.4% of V122I carriers had a diagnosis of any one of the common manifestations, including polyneuropathy (7.9%).CONCLUSIONSV122I carriers, historically associated with a predominantly cardiac phenotype of hATTR amyloidosis, have a significantly increased risk of polyneuropathy.

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Abstract 131: Cognitive Impairment Predicts Mortality in Patients with Heart Failure

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.9.suppl_2.131 ◽

2016 ◽

Vol 9 (suppl_2) ◽

Author(s):

Howard Lan ◽

Lee Ann Hawkins ◽

Helme Silvet

Keyword(s):

Heart Failure ◽

Cognitive Impairment ◽

Proportional Hazards ◽

Cox Regression ◽

Cox Proportional Hazards ◽

Mortality Data ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Study Population

Introduction: In our previously published study, we evaluated a Veteran cohort of 250 outpatients with heart failure (HF) and found 58% (144 of 250) incidence of previously undiagnosed cognitive impairment (CI). Previous studies have suggested that HF patients with CI have worse clinical outcomes including higher mortality but this has not been studied in the Veteran population. Methods: Current study was designed to prospectively follow this cohort of 250 patients. Cognitive function was previously evaluated in all patients at baseline using the St. Luis University Mental Status (SLUMS) exam. The primary outcome for this follow-up study was all-cause mortality. Data analysis including Cox regression analysis and Kaplan-Meier curves were generated using SPSS. Results: The study population was predominantly Caucasian (72%, 179 of 250) and male (99%, 247 of 250) with mean age of 69 ± 10 years. Mean follow up was 31 ± 11 months. During follow up, 26% (64 of 250) of patients died. Univariate and multivariate Cox proportional hazards regression analyses were performed and shown in Table 1. Using the SLUMS score, subjects were stratified into three groups: no CI (42%, 106 of 250), mild CI (42%, 104 of 250), and severe CI (16%, 40 of 250). Kaplan-Meier survival curves were generated to compare the three CI groups in Figure 1. Conclusion: Current study demonstrates that CI is an independent risk factor for mortality in outpatient HF patients. This is an important finding because CI is commonly unrecognized in this vulnerable population. Routine CI screening could help to identify those who are at greater risk for worse outcomes. Future studies are needed to derive possible interventions to improve outcomes in these patients.

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Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: seven-year follow up of the UK Biobank cohort

10.1101/19008458 ◽

2019 ◽

Author(s):

Richard J. Shaw ◽

Breda Cullen ◽

Nicholas Graham ◽

Donald M. Lyall ◽

Daniel Mackay ◽

...

Keyword(s):

Emotional Support ◽

Living Arrangements ◽

Hospital Admissions ◽

Cox Regression ◽

Living Alone ◽

Uk Biobank ◽

Self Harm ◽

The Uk ◽

The Relationship

AbstractBackgroundThe association between loneliness and suicide is complex, poorly understood, and there are no prior longitudinal studies. We aimed to investigate the relationship between living alone, loneliness and emotional support as predictors of death by suicide and self-harm.MethodsBetween 2006 and 2010 UK Biobank recruited over 0.5m people aged 37-73. This data was linked to prospective hospital admission and mortality records. Adjusted Cox regression models were used to investigate the relationship between self-reported measures of loneliness, emotional support and living arrangements and death by suicide and self-harm.ResultsFor women, there was no evidence that living arrangements, loneliness or lack of emotional support were associated with death by suicide. However, for men, both living alone (Hazard Ratio (HR) 2.19 95%CI 1.47-3.27) and with non-partners (HR 2.17 95%CI 1.28-3.69) were associated with death by suicide, independently of loneliness, which had a modest relationship with suicide in men (HR 1.45 95%CI 0.99-2.12). Associations between living alone and self-harm were explained by health for women, and by health, loneliness and emotional support for men. In fully adjusted models, loneliness was associated with hospital admissions for self-harm in both women (HR 1.90 95%CI 1.58-2.29) and men (HR 1.75 95%CI 1.41-2.18).ConclusionsFor men -but not for women- living alone or with a non-partner increased the risk of suicide, a finding not explained by loneliness. Loneliness may be more important as a risk factor for self-harm than for suicide, and appears to mitigate against any protective effect of cohabitation.

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Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank

10.1101/2020.04.19.20071936 ◽

2020 ◽

Author(s):

Seyedeh M. Zekavat ◽

Michael Honigberg ◽

James Pirruccello ◽

Puja Kohli ◽

Elizabeth W. Karlson ◽

...

Keyword(s):

Blood Pressure ◽

Observational Studies ◽

Mendelian Randomisation ◽

List Type ◽

Uk Biobank ◽

Increased Risk ◽

Reduce Risk ◽

Novel Coronavirus ◽

The Uk

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.

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The association of nine amino acids with cardiovascular events in Finnish men in a 12-year follow-up study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab562 ◽

2021 ◽

Author(s):

Raimo Jauhiainen ◽

Jagadish Vangipurapu ◽

Annamaria Laakso ◽

Teemu Kuulasmaa ◽

Johanna Kuusisto ◽

...

Keyword(s):

Cardiovascular Disease ◽

Amino Acids ◽

Ischemic Stroke ◽

Amino Acid ◽

Cox Regression ◽

Cox Regression Analysis ◽

Increased Risk ◽

Artery Disease

Abstract Background and aims To investigate the significance of nine amino acids as risk factors for incident cardiovascular disease events in 9,584 Finnish men. Materials and Methods A total of 9,584 men (age 57.4±7.0 years, body mass index 27.2±4.2 kg/m 2) from the METSIM study without cardiovascular disease and type 1 diabetes at baseline were included in this study. A total of 662 coronary artery disease (CAD) events, 394 ischemic stroke events, and 966 cardiovascular disease (CVD, CAD and stroke combined) events were recorded in a 12.3-year follow-up. Amino acids were measured using nuclear magnetic resonance platform. Results In Cox regression analysis phenylalanine and tyrosine were significantly associated with increased risk of CAD and CVD events, and phenylalanine with increased risk of ischemic stroke after the adjustment for confounding factors. Glutamine was significantly associated with decreased risk of stroke and CVD events and nominally with CAD events. Alanine was nominally associated with CAD events. Conclusion We identified alanine as a new amino acid associated with increased risk of CAD and glutamine as a new amino acid associated with decreased risk of ischemic stroke. We also confirmed that phenylalanine and tyrosine were associated with CAD, ischemic stroke, and CVD events.

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