Excess Risk Of Cardiovascular Disease Research Articles

Association of hyperuricemia with risk of cardiovascular disease according to the number of risk factors within target range

Background and aimsRisk factor modification may decrease the risk of cardiovascular disease (CVD). Whether risk factor modification can mitigate the effect of hyperuricemia on CVD is unclear. This study aimed to investigate the risk of CVD among individuals with hyperuricemia, according to risk factors on target, compared with controls without hyperuricemia. Methods and resultsThis prospective study included 91,722 participants free of CVD at baseline (2006–2007) of the Kailuan study. Individuals with hyperuricemia were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking, physical activity, healthy diet, guideline-recommended levels of body mass index, blood pressure, fasting blood glucose, and total cholesterol). During a median follow-up of 13.00 years, 671 out of 6740 individuals (9.96%) with hyperuricemia and 6301 out of 84,982 control subjects (7.41%) had incident CVD. Compared with control subjects without hyperuricemia, individuals with hyperuricemia who had 4 or 5 to 7 risk factors on target had no significant excess CVD risk, the hazard ratio (HR) (95% confidence internal [CI]) was 0.93 (0.79–1.10) and 0.88 (0.71–1.10), respectively. Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors on target, the HR of CVD associated with per additional risk factor within target range was 0.82 (95% CI, 0.77–0.87). Similar results were yielded for CVD subtypes. ConclusionsAmong individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors within target.

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects

BackgroundEvidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects.MethodsWe aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26).ResultsWomen with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association.ConclusionsOur data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Degree of Risk Factor Control and Incident Cardiovascular Diseases in Patients With Hypertension

ObjectiveTo investigate whether joint risk factor control could reduce the excess risk of cardiovascular disease (CVD) in patients with hypertension. Patients and MethodsA total of 75,293 patients with diagnosed hypertension from the UK Biobank study were included, matched with 256,619 nonhypertensive controls, and followed up until May 31, 2021. Seven risk factors were measured to define joint risk factor control, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. ResultsAmong hypertensive patients, 14% to 24% lower risks of CVD outcomes were associated with each additional risk factor control. In the Cox proportional hazards models, adjusted hazard ratios for patients with 6 or more risk factor controls compared with patients having 2 or less risk factor controls were 0.49 (95% CI, 0.45 to 0.55) for CVD, 0.51 (95% CI, 0.45 to 0.57) for coronary heart disease, 0.48 (95% CI, 0.38 to 0.60) for stroke, and 0.34 (95% CI, 0.26 to 0.44) for CVD mortality. The excess risks of CVD outcomes in patients with hypertension were diminished to nonsignificant or even lower compared with controls if achieving 6 or more risk factor controls. Men experienced stronger protective associations of joint risk factor control on risks of CVD than women (P<.001 for interaction). ConclusionThe joint risk factor control is associated with lower risks of CVD, and a high degree of risk factor control may considerably attenuate the excess risk of CVD among patients with hypertension.

QRISK3 underestimates the risk of cardiovascular events in patients with COPD

BackgroundPatients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease (CVD). The extent to which the excess CVD risk is captured by risk factors in QRISK,...

Abstract 12995: South Asian Representation in Cardiovascular Disease Randomized Controlled Trials

Introduction: South Asian individuals are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared to individuals of European descent. Although US practice guidelines uniquely recognize South Asian ancestry as a risk-enhancing factor for ASCVD, the degree to which South Asian individuals are included in clinical trials is unknown. We sought to evaluate South Asian representation in major cardiovascular disease (CVD) randomized controlled trials (RCTs) reported in major medical journals. Hypothesis: South Asian individuals are under-represented relative to the global South Asian population in CVD RCTs. Methods: We extracted citations of CVD RCTs reported from 2018 to 2022. Studies were identified as RCTs based on reported randomization of participants and the publication of post-randomization data. We determined self-reported representation rates for South Asian individuals across all studies and further stratified representation rates by clinical trial phase, type of intervention under investigation, and country of origin. Post-randomization participant representation rates were estimated for South Asian individuals and compared to other self-reported racial/ethnic groups. Results: 588,329 participants were enrolled across 128 included trials. Conditions studied included CVA (17.97%), HF (12.50%), CAD (11.72%), HTN (7.81%), ASCVD screening/prevention (7.81%), and others. 2,753 of all CVD RCT participants were South Asian individuals, corresponding to a representation rate of 0.47%. No South Asian individuals had available post-randomization data, whereas post-randomization data were reported for 164,035 white individuals, 20,459 Black individuals, and 6,040 Hispanic individuals. Conclusions: Although South Asian individuals comprise nearly a quarter of the global population and have well-documented excess CVD risk, they represent a small minority of CVD trial participants. No RCTs reported South Asian participant-level data, which limits the generalizability of study findings to South Asians.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

POSSIBLE PREDICTORS CONTRIBUTING TO ATRIAL FIBRILLATION OCCURRENCE IN HYPERTENSIVE PATIENTS

Objective: Arterial hypertension (HT) and atrial fibrillation (AF) are two important public health problems. Their prevalence is increasing worldwide, and often coexist in the same patient. HT and AF are strikingly related to an excess risk of cardiovascular disease and death. HT ultimately increases the risk of AF and several factors underlying the higher risk of AF in patients with HT are still incompletely known. HT is one of the main reasons for the remodeling process in and makes a significant contribution to the development of structural changes of the heart. The aim of this study is to identify possible predictors of paroxysmal/persistent AF occurrence and progression in hypertensive patients. Design and method: In this study where enrolled 219 hypertensive patients with non-valvular paroxysmal/persistent AF (mean age 63.6±7.4). As a control group 94 patients with HT and without AF were also examined. Echocardiography examination and 24-hour ambulatory Holter monitoring ECG were registered in each patient. The database consisting of 19 indicators that characterize the clinical, hemodynamic and structural-functional state of the heart, as well as markers of inflammation and fibrosis was created. Data were analyzed by SPSS 13 program using logistic analysis by odds ratio (OR). Results: The obtained results showed that in hypertensive patients with paroxysmal/persistent AF, OR of more episodes of hypertensive crises, deterioration of electrical remodeling and left ventricular (LV) diastolic function, as well as a significant increase in the levels of concentrations of inflammatory and fibrosis markers in comported with hypertensive patients without AF were detected. Conclusions: The multifactorial analysis revealed significant impact of LA and LV dysfunction, inflammation and fibrosis as well as hypertensive crises on the possible risk of AF occurrence and progression in hypertensive patients.

POSSIBLE PREDICTORS CONTRIBUTING TO AF OCCURRENCE IN HYPERTENSIVE PATIENTS

Objective: Arterial hypertension (AH) and atrial fibrillation (AF) are two important public health problems. Their prevalence is increasing worldwide, and often coexist in the same patient. AH and AF are strikingly related to an excess risk of cardiovascular disease and death. AH ultimately increases the risk of AF and several factors underlying the higher risk of AF in hypertensive patients are still incompletely known. AH is one of the main reasons for the remodeling process in these patients and makes a significant contribution to the development of structural changes. The aim of this study is to identify possible predictors of paroxysmal/persistent AF occurrence and progression in hypertensive patients Design and method: In this study where enrolled 219 hypertensive patients with non-valvular paroxysmal/persistent AF (mean age 63.6 ±7.4) who were hospitalized at Research Institute of Cardiology between 2016 and 2018 year. As a control group 94 hypertensive patients without AF were also examined. After the enrollment the echocardiography examination and 24-hour ambulatory Holter monitoring ECG were registered in each patient. We measured plasma indexes of inflammation (hsCRP, IL-6) and fibrosis marker TGF-beta1. The database consisting of 19 indicators that characterize the clinical, hemodynamic and structural-functional state of the heart, as well as markers of inflammation and fibrosis was created. All data were analyzed by SPSS 13 and EXCEL - 2013 programs using logistic analysis by odds ratio (OR). Results: The obtained results showed that in hypertensive patients with paroxysmal /persistent AF, OR of more episodes of hypertensive crises, deterioration of electrical remodeling and LV diastolic function, as well as a significant increase in the levels of concentrations of inflammatory and fibrosis markers in comported with hypertensive patients without AF were detected (tabl.1). Conclusions: The multifactorial analysis revealed significant impact of left atrial and ventricular dysfunction, inflammation and fibrosis as well as hypertensive crises on the possible risk of AF occurrence and progression in hypertensive patients

Sex differences in cardiovascular risk, lifestyle, and psychological factors in patients with type 2 diabetes: the Fukuoka Diabetes Registry

BackgroundThe excess risk of cardiovascular diseases associated with diabetes is greater in women than in men. The present study aimed to examine sex differences in the control of cardiovascular risk factors, as well as lifestyle and psychological factors, in patients with type 2 diabetes.MethodsA total of 4923 Japanese patients with type 2 diabetes were included in this cross-sectional study. Female/male differences in cardiovascular risk factor levels, and corresponding odds ratios for achieving recommended ranges for preventing cardiovascular diseases and having unhealthy lifestyle and psychological factors were computed by linear and logistic regression models.ResultsWomen were less likely than men to achieve recommended ranges for glycated hemoglobin, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and obesity-related anthropometric indices such as body mass index and waist circumference, but were more likely than men to be on target for high-density lipoprotein cholesterol and triglycerides. Women were also more likely than men to have an unhealthy lifestyle and psychological factors, including less dietary fiber intake, less leisure-time physical activity, shorter sleep duration, more constipation, and more depressive symptoms. Similar findings were observed when the participants were subgrouped by age (< 65 and ≥ 65 years) and past history of cardiovascular disease.ConclusionsWe observed significant sex differences for a range of cardiovascular risk factors, as well as lifestyle and psychological factors, suggesting the importance of adopting a sex-specific approach for the daily clinical management of diabetes.

Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges’ g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results – 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93–7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers – i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges’ gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention – which harnessed technology to maximize access and minimize resources – produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches.Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.

Sex Differences in Cardiovascular Risk Associated With Prediabetes and Undiagnosed Diabetes

Women with Type 2 diabetes (T2D) face up to 50% higher risk of cardiovascular disease than men. This study evaluated the extent to which prediabetes and undiagnosed T2D are associated with a greater excess risk of cardiovascular disease in women versus in men. Data were pooled from 18,745 cardiovascular disease-free individuals from the Atherosclerosis Risk in Communities Study, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. The risk of coronary heart disease, ischemic stroke, and atherosclerotic cardiovascular disease (coronary heart disease or stroke) associated with prediabetes or undiagnosed T2D was estimated using Cox models adjusting for sociodemographic factors, concomitant risk factors, medication use, and menopausal status. Data were collected in 2022, and the analysis was performed in 2023. During a median follow-up of 18.6 years, the associations between prediabetes and risk of atherosclerotic cardiovascular disease were only significant in women (hazard ratio=1.18, 95% CI=1.01, 1.34, p=0.03) but not in men (hazard ratio=1.08, 95% CI=1.00, 1.28, p=0.06) (p-interaction=0.18). The associations between undiagnosed T2D and cardiovascular disease outcomes were significant in both sexes, but the effect was more pronounced in women (coronary heart disease: hazard ratio=1.83, 95% CI=1.4, 2.41, p<0.0001 in women vs hazard ratio=1.6, 95% CI=1.38, 2.07, p=0.007 in men; stroke: hazard ratio=1.99, 95% CI=1.39, 2.72, p<0.0001 vs hazard ratio=1.81, 95% CI=1.36, 2.6, p<0.0001; atherosclerotic cardiovascular disease: hazard ratio=1.86, 95% CI=1.5, 2.28, p<0.0001 vs hazard ratio=1.65, 95% CI=1.4, 1.98, p<0.0001) (all p-interactions≤0.2). Both White and Black patients exhibit similar sex differences. Prediabetes or undiagnosed T2D was associated with a greater excess risk of cardiovascular disease in women than in men. The sex differential in cardiovascular disease risk among those without the T2D diagnosis suggests the need for sex-specific guidelines in T2D screening and treatment.

Lifestyle Trajectories Are Associated with Incidence of Cardiovascular Disease: Highlights from the ATTICA Epidemiological Cohort Study (2002-2022).

The study aimed to assess the trajectories of lifestyle characteristics and their association with 20-year cardiovascular disease (CVD) incidence. In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants; of those, 1988 had complete data for CVD. The 20-year CVD incidence was 3600 cases/10,000 individuals; the man-to-woman ratio was 1.25, with the peak difference in the 35-45 age group (i.e., 2.1); however, a reversal of the trend was observed in the age-groups 55-65 and 65-75, with a resumption of an almost equal incidence in those >75 years. In multi-adjusted analysis, age, sex, abnormal waist circumference, hypercholesterolemia, hypertension, and diabetes were positively associated with 20-year CVD risk, explaining 56% of the excess CVD risk, whereas an additional 30% was attributed to lifestyle trajectories; being physically active throughout life-course and being close to the Mediterranean diet were protective, while continuous smoking was detrimental against CVD risk. Mediterranean diet adherence protected against CVD development even if not sustained, while quitting smoking or engaging in physical activities during the 20-year observation did not offer any significant protection. A life-course personalized approach that is cost-effective and long-term sustained is needed to prevent CVD burden.

Presence of tophi and carotid plaque were risk factors of MACE in subclinical artherosclerosis patients with gout: a longitudinal cohort study.

Patients with gout carry an excess risk for cardiovascular disease (CVD), but the contribution of subclinical atherosclerosis to the CVD risk has never been reported. In this study, we aimed to explore the predictive factors for incident major adverse cardiovascular events (MACE) in gout patients without a previous history of CVD or cerebral vascular disease. A single-center, long-term follow-up cohort analysis was performed to assess subclinical atherosclerosis at baseline since 2008. Patients with a previous history of CVD or cerebrovascular disease were excluded. The outcome of the study was the first MACE. The presence of subclinical atherosclerosis was assessed by carotid plaque (CP), and carotid intima-media thickness (CMIT) was determined by ultrasound. An ultrasound scan of bilateral feet and ankles was performed at baseline. The association between tophi, carotid atherosclerosis, and the risk of developing incident MACE was evaluated using Cox proportional hazards models with adjustment for the CVD risk scores. A total of 240 consecutive patients with primary gout were recruited. Their mean age was 44.0 years, with male predominance (238, 99.2%). During a median follow-up of 10.3 years, incident MACE was ascertained in 28 (11.7%) patients. In a Cox hazards model, controlling for the CV risk scores, the presence of at least two tophi (HR, 2.12-5.25, p < 0.05) and carotid plaque (HR, 3.72-4.01, p < 0.05) were identified as independent predictors of incident MACE in gout patients. The presence of at least two tophi and carotid plaque on an ultrasound could independently predict MACE in addition to conventional cardiovascular risk factors in gout patients.

Correlation between HbA1c and lipid profile in patients with Type 2 diabetes mellitus

Background: Diabetes mellitus is one of the greatest health threats of recent times for global population, T2DM is associated with two to four excess risk of cardiovascular disease, Serum lipids are frequently abnormal and are likely to contribute to the risk of coronary artery disease, and there an 18% increased risk of cardiovascular disease for each 1% increase of HbA1c in diabetic population, Method and patient: this is across sectional study which was carried out on 100 diabetic patients ,62 male and 38 female with age from 38-75years, after fasting of at least 8 hours, fasting blood sugar, HbA1C and lipid profile were measured. Result: patients were divided into two groups; the controlled group with HbA1c of 7% or less, and uncontrolled group with HbA1c of more than 7% ,the controlled group include 28% of the patients while the uncontrolled group include 72% of the patients with mean age of 50.50±12.60 and 53.94±7.99 respectively, with no significant difference(p-value=0.187), while there was significant difference in lipid profile between the two groups. Conclusions: most diabetic patients are uncontrolled and dyslipidemia, and HbA1c is used as a dual marker for dyslipidemia and diabetic control.

Severe Infection and Risk of Cardiovascular Disease: A Multicohort Study.

The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction. We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk. In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36-9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40-1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82-10.03] during the first month; HR, 1.41 [95% CI, 1.34-1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort. Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded.

Abstract MP60: Prediabetes and Undiagnosed Diabetes Predisposing Women to Excess Risk of Cardiovascular Disease

Objective: Women with type 2 diabetes (T2DM) have a 25-50% higher risk of cardiovascular disease (CVD) than their men counterparts. The reasons for this sex disparity are incompletely understood. We sought to examine if pre-diabetes (preDM) and undiagnosed T2DM are associated with a greater magnitude of CVD risk in women than in men. Methods: We pooled CVD-free individuals (N=18,745) from the Atherosclerosis Risk in Communities, the Multi-Ethnic Study of Atherosclerosis, and the Jackson Heart Study. CVD outcomes included incident coronary heart disease (CHD) (myocardial infarction, CHD death, or cardiac procedures including percutaneous coronary interventions, bypass surgery, or coronary revascularization), stroke (ischemic or hemorrhagic stroke), and a composite atherosclerotic CVD (ASCVD) (any CHD condition or stroke). Multivariable Cox models examined the outcomes associated with preDM (fasting glucose [FG] 100-125 mg/dL or HbA1c 5.7-6.4%) or undiagnosed T2DM (FG ≥126 mg/dL or HbA1c ≥6.5% and without a DM diagnosis or anti-diabetes medication use) adjusted for age, race/ethnicity, education, BMI, blood pressure, total cholesterols, smoking, anti-hypertensive and lipid-lowering medications, and cohort indicator. An interaction term sex x preDM or undiagnosed DM was added to models to test the sex modifying effect. We consider p-interaction&lt;0.2 as significant. Results: During a median follow-up of 17 years, the adjusted model showed that preDM was significantly associated with a higher risk of CHD (Hazard ratio 1.09, 95%CI 1.04-1.14), stroke (1.08, 1.04-1.13), and ASCVD (1.09, 1.04-1.14) in women, but not in men (1.04, 0.99-1.1 for CHD, 1.03, 0.98-1.08 for stroke, and 1.03, 0.98-1.09 for ASCVD, respectively). Undiagnosed T2DM was significantly associated with the risk of CHD (1.27, 1.16-1.4 in women and 1.17, 1.05-1.3 in men), stroke (1.32, 1.21-1.45 in women and 1.2, 1.09-1.32 in men), and ASCVD (1.27, 1.16-1.4 in women and 1.15, 1.03-1.29 in men) in both sexes but with more pronounced effect in women (P-interactions ≤0.11). In racial-stratified analysis, a higher magnitude of CVD risk associated with preDM or undiagnosed DM was also found in non-Hispanic (NH) white women and NH-black women than in their men counterparts. Conclusions: PreDM and undiagnosed DM predispose women to excess CVD risk, possibly due to women’s higher susceptibility to metabolic dysfunction at a lower glucose level and the prolonged unmanaged time for risk factors relative to men. T2DM screening and risk factor control should be enhanced in both sexes to reduce future CVD risk, particularly in women.

Abstract P162: Sex Differences in Cardiometabolic Biomarkers During Pre-Diabetes

Background: Diabetes (DM) diminishes female protection against cardiovascular disease (CVD). Women with DM face excess CVD risk than men partly due to women’s greater deterioration in risk factors before DM. In this study, we compared sex differences in biomarkers that reflect distinct pathophysiological pathways during the pre-diabetes (pre-DM) stage. Method: A cross-sectional analysis was performed based on pooled data from Atherosclerosis Risk in Communities Study and the Jackson Heart Study. We used multivariable linear regressions to examine the associations between sex and biomarkers (log-transformed) representative of inflammation, lipoprotein, adipokine, kidney function, cardiac injury/stress, and thrombosis, adjusted for age, race, and BMI, among CVD-free individuals with pre-DM. We validated the results in a sensitivity analysis, including those that eventually progressed into DM during the follow-up. We used the false discovery rate method to adjust multiple comparisons. Results: Among 5975 individuals with pre-DM, the mean age was 54.2 years, 2853 (48%) were women, and 2022 (34%) were non-Hispanic blacks. In the adjusted models, inflammatory biomarkers, including high-sensitivity c-reactive proteins (β coefficient 0.2, P=2.9 x 10 -9 ), fibrinogen (β 0.19, P=2.8E-12), and absolute lymphocyte (β 0.25, P=2.54 x 10 -7 ), and cardiac injury/stress biomarker, NT-proBNT (β 0.14, P=0.0002) were higher in women than men with pre-DM. Additionally, lipoprotein(a) (β 0.19, P=4.96 x 10 -13 ) and apolipoproteins A1 (β 0.61, P=2.81x 10 -120 ), and adipokines including leptin (β 1.1, P=2.62 x 10 -123 ) and adiponectin (β 0.56, P=1.94 x 10 -12 ) were all higher in women with pre-DM. In contrast, kidney function markers, albumin (β -0.24, P=2.79 x 10 -9 ) and creatinine (β -1.1, P=1x 10 -100 ), and thrombosis biomarker, homocysteine (β -0.5, P=9.09 x 10 -19 ) were higher in men with pre-DM than in their women counterparts. These sex differences remained generally unchanged among 2320 individuals that progressed into DM. Conclusion: Biomarkers differ significantly between sexes during the pre-DM state. The inflammatory, lipoprotein, adipokine, and cardiac stress biomarkers were higher in women with pre-DM, while kidney function and thrombosis biomarkers were higher in men with pre-DM. Future mechanistic studies are warranted to delineate pathophysiological pathways characterized by these biomarkers contributing to sex disparities of CVD risk in DM.

Abstract P523: Joint Improvement Scale of Loneliness and Traditional Risk Factor Control, and Incident Cardiovascular Disease in Diabetes Patients

Background: Emerging evidence has shown a higher rate of loneliness and social isolation among patients with diabetes, and loneliness and isolation has been associated with high risk of cardiovascular disease (CVD). Hypothesis: We investigated the extent to which the risks of CVDs could be lowered by improvement of loneliness and social isolation, individually or in conjunction with controlling traditional risk factors in diabetic patients. Methods: A total of 18,783 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess the improvement of loneliness and isolation status, respectively. The degree of traditional risk-factor control was defined as the number of glycated hemoglobin (HbA1c), blood pressure (BP), low-density-lipoprotein cholesterol (LDL-C), smoking and microalbumin reaching the target range. Results: During a mean follow-up of 10.7 years, 3,129 incident total CVD events were documented, including 2,627 coronary heart disease (CHD) and 721 stroke. We found that each point increase in loneliness improvement scale was significantly associated with an 11% lower risk of CVD (HR, 95%CI, 0.89, 0.84-0.93) and a 12% lower risk of CHD (HR, 95%CI, 0.88, 0.83-0.93), but not with stroke. The improvement scale of social isolation was not associated with CVDs. Loneliness showed greater relative importance than lifestyle risk factors in preventing CVD among diabetic patients. We found a significant additive interaction between loneliness and the degree of traditional risk-factor control on the risk of CVDs ( P for additive interaction=0.002). Moreover, compared with non-diabetes controls, the diabetes-related excess CVD risk might be eliminated when three or more risk factors were controlled in non-lonely patients, but more than four are required in lonely patients. Conclusion: Among diabetes patients, improvement of loneliness is associated with a lower risk of CVD and shows an additive interaction with traditional risk factor control.

Association between coeliac disease and cardiovascular disease: prospective analysis of UK Biobank data

ObjectivesTo investigate whether people with coeliac disease are at increased risk of cardiovascular disease, including ischaemic heart disease, myocardial infarction, and stroke.DesignProspective analysis of a large cohort study.SettingUK Biobank database.Participants469...