Incidence Of Cardiovascular Disease In Patients Research Articles

The potential protective role of vitamin D and calcium supplements in reducing cardiovascular disease risk among elderly patients with osteopenia

BackgroundCardiovascular disease and low bone mineral density are major health problems in the elderly. These two conditions are considered independent of each other and age-related diseases. The aim of this study is to investigate the association between low bone mineral density (BMD) and cardiovascular disease (CVD) incidents, and the effect of vitamin D and calcium supplement on the incidence of CVD in patients with low BMD.MethodsA total of 1047 patients (597 females/450 males) with the age of 65 years and more were diagnosed with osteopenia for 13 years or more. The study also included 220 patients (107 females/113 males) with osteopenia who already took calcium and vitamin D continually since their diagnosis. BMD was measured by dual-energy X-ray absorptiometry. The incidence of any cardiovascular diseases in the study patients and the presence of corresponding risk factors were collected and analyzed.ResultsIn both elderly Arab females and males, there was an association between total hip and femoral neck BMD and the possibility to have CVD. On the other hand, the results showed that patients who use calcium and vitamin D supplements showed a significant reduction in the incidence of CVD comparing to the non-treated patients.ConclusionLow total hip and femoral neck BMD were associated with a higher chance to have CVD incidents in both elderly Arab males and females; moreover, calcium and vitamin D supplements have a possible protective role in reducing cardiovascular disease in elderly patients with osteopenia.

Association of serum concentrations of remnant cholesterol with incident cardiovascular disease in patients with rheumatoid arthritis: A real-world data from 2001 to 2022

BackgroundRemnant cholesterol (RC) promotes cardiovascular disease (CVD) in the general population, but its role among rheumatoid arthritis (RA) patients remains unknown. We aimed to investigate circulating RC levels associated with incident CVD among Chinese patients with RA. MethodsA total of 1018 RA patients free of baseline CVD were included and followed up in a prospective RA CVD cohort from 2001 to 2022. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs). ResultsRA patients had a mean age of 53.9 years, and 802 (78.8%) were females. After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58–3.35) per 1 mmol/L increase, and 2.40 (1.36–4.25) and 2.81 (1.60–4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively. ConclusionsCirculating RC levels are positively associated with incident CVD among Chinese RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.

Risk factor control and incident cardiovascular disease in patients with diabetes: Sex-specific relations.

Women with diabetes are at higher risk of cardiovascular diseases (CVD) than men with diabetes; however, the sex difference in the association between the degree of risk factor control and the risk of CVD in patients with diabetes is unclear. In total, 17 260 participants diagnosed with diabetes from the UK Biobank were included and matched with 86 300 non-diabetes controls based on age, sex and assessment centre. The main exposure was the number of risk factors within the target range, including glycated haemoglobin level <53 mol/mol (7%), blood pressure <140/90 mm/Hg, low-density lipoprotein cholesterol <100 mg/dl, non-current smoking and absence of microalbuminuria. During a median follow-up of 13.3 years, a total of 3338 incident CVD cases, including 2807 ischaemic heart disease and 793 strokes, were documented. A more stringent control of risk factors was significantly associated with a lower risk of incident CVD, and such an association was significantly stronger in women than men. Compared with non-diabetes participants, the diabetes-related risk of CVD appeared to be eliminated if more than three risk factors were well controlled among women and men with diabetes. Moreover, clinical biomarkers (e.g. glycated haemoglobin and blood pressure) showed greater relative importance than other factors in women, whereas socio-economic and psychological factors (e.g. education and depression) exhibited similar relative importance to clinical biomarkers in men with diabetes. Our findings highlighted the importance of raising awareness of sex differences in the management of CVD risk factors among patients with diabetes.

Gout is associated with increased cardiovascular risk: results from analysis of the CPRD dataset

Abstract Background Gout, a common crystal arthropathy, has been associated with higher cardiovascular risk. However, the degree to which this risk is potentially mediated by traditional risk factors, and whether this risk differs across individual cardiovascular disorders (CVD), inclusive of heart failure, is unclear. Purpose We aimed to determine the risk of incident cardiovascular disease in patients with newly diagnosed gout, whether this varied across a range of cardiovascular disorders, and the potential impact of traditional risk factors. Methods We used linked primary and secondary electronic health records from 22 million individuals in the Clinical Practice Research Datalink (CPRD) to assemble a cohort of individuals newly diagnosed with gout between 01/01/2000 and 31/12/2017 and free of cardiovascular disorders (CVD) up to 12 months after diagnosis, and up to five individuals matched on age, sex, socioeconomic status and region, with follow-up until 30/06/2019. We investigated the incidence of twelve cardiovascular outcomes and used Cox-proportional hazards models to examine differences in patients with and without gout. In sensitivity analyses, models were further adjusted for known cardiovascular risk factors (blood pressure, BMI, smoking, cholesterol, and type 2 diabetes). Results We identified 153 645 individuals with Gout and 714 192 matched controls. Of these, 31479 people with and 106 520 without gout developed incident CVD during a median of 6.5 years of follow-up. Patients with gout had a higher risk of cardiovascular outcomes than controls: hazard ratio (HR) [95% confidence interval (CI)] 1.57 [1.52, 1.63]. Excess cardiovascular risk disproportionally affected women (HR in women: 1.88 [1.75, 2.02], HR in men: 1.50 [1.40, 1.62]), and was highest in the very young (HR in people aged 45 years or less: 2.20 [1.91, 2.54]) (Figure 1). Excess risk was visible across all 12 cardiovascular diseases investigated, and was particularly pronounced for heart failure, arrhythmias, and valve disease (HR for heart failure: 1.84 [1.73, 1.96], HR for atrial fibrillation and flutter: 1.81 [1.72, 1.91], HR for valve diseases: 1.83 [1.71, 1.97]). Patients with gout presented with on average 3 units higher body mass index than matched controls, and had higher prevalence of chronic kidney disease, dyslipidaemia, and hypertension. In sensitivity analyses, adjusting for known cardiovascular risk factors attenuated the strength of the associations by around half, although gout remained an independent CVD risk factor. Conclusion Patients with gout present a higher risk of developing a range of cardiovascular outcomes, in particular heart failure, arrhythmias, and valve disease. These findings suggest patients with gout should have formal CV risk assessment, and stronger attention to lifestyle interventions to mitigate future atherosclerotic and cardiorenal risks.Fig1 CVD rates &amp; HRs in gout vs controls

Effects of social determinants of health on mortality and incident liver-related events and cardiovascular disease in steatotic liver disease.

Social determinants of health (SDOH) are becoming increasingly recognised as mediators of human health. In the setting of metabolic dysfunction-associated steatotic liver disease (MASLD), most of the literature on SDOH relates to individual-level risk factors. However, there are very limited data on neighbourhood-level SDOH in MASLD. To assess whether SDOH impact fibrosis progression in patients who already have MASLD. This was a retrospective cohort study of patients with MASLD seen at Michigan Medicine. The primary predictors were two neighbourhood-level SDOH, 'disadvantage' and 'affluence'. The primary outcomes were mortality, incident liver-related events (LREs) and incident cardiovascular disease (CVD). We modelled these outcomes using Kaplan-Meier statistics for mortality and competing risk analyses for LREs and CVD, using a 1-year landmark. We included 15,904 patients with MASLD with median follow-up of 63 months. Higher affluence was associated with lower risk of overall mortality (hazard ratio 0.49 [0.37-0.66], p < 0.0001 for higher vs. lower quartile), LREs (subhazard ratio 0.60 [0.39-0.91], p = 0.02) and CVD (subhazard ratio 0.71 [0.57-0.88], p = 0.0018). Disadvantage was associated with higher mortality (hazard ratio 2.08 [95% confidence interval 1.54-2.81], p < 0.0001 for the highest vs. lowest quartile) and incident CVD (subhazard ratio 1.36 [95% confidence interval 1.10-1.68], p < 0.0001). These findings were robust across several sensitivity analyses. Neighbourhood-level SDOH are associated with mortality, incidence of LREs and incident CVD in patients with steatotic liver disease. Interventions aimed at disadvantaged neighbourhoods may improve clinical outcomes.

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Associated with Disease Activity and Risk of Incident Cardiovascular Disease in Patients with Systemic Lupus Erythematosus.

To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLEdisease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.

Asthma and increased risk of myocardial infarction and mortality among hypertensive Korean patients.

This study aimed to evaluate the effects of asthma on cardiovascular disease incidence in patients with hypertension. A total of 639,784 patients with hypertension from the Korea National Health Insurance Service database were included, of whom 62,517 had history of asthma after propensity score matching. The risks of all-cause mortality, myocardial infarction (MI), stroke, and end-stage renal disease (ESRD) were assessed according to the presence of asthma, long-acting β2-agonist (LABA) inhaler usage, and/or systemic corticosteroid usage for up to 11 years. In addition, whether these risks were modified by average blood pressure (BP) levels during the follow-up period was examined. Asthma was associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.203; 95% confidence interval [CI], 1.165-1.241) and MI (HR, 1.244; 95% CI, 1.182-1.310) but not the risk of stroke or ESRD. LABA inhaler usage was associated with a higher risk of all-cause mortality and MI, and systemic corticosteroids usage showed a higher risk of ESRD as well as all-cause mortality and MI among hypertensive patients with asthma. Compared to patients without asthma, there was a graded increase in the risk of all-cause mortality and MI in those with asthma without LABA inhaler/systemic corticosteroid usage and in those with asthma with LABA inhaler/systemic corticosteroid usage. These associations were not significantly modified by BP levels. This nationwide population-based study supports that asthma may be a clinical factor that increases the risk of poor outcomes in patients with hypertension.

Association of Serum Calcium and Phosphate With Incident Cardiovascular Disease in Patients With Hypoparathyroidism

The pathophysiological basis for the increased incidence of cardiovascular disease in patients with chronic hypoparathyroidism is poorly understood. To evaluate associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product with the odds of developing cardiovascular events in patients with chronic hypoparathyroidism with ≥1 calcitriol prescription, we conducted a retrospective nested case-control study of patients who developed a cardiovascular event and matched controls without an event. The primary outcome was the instance of cardiovascular events. An electronic medical record database was used to identify 528 patients for the albumin-corrected serum calcium analysis and 200 patients for the serum phosphate and calcium-phosphate product analyses. Patients with ≥67% of albumin-corrected serum calcium measurements outside the study-defined 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) range had 1.9-fold higher odds of a cardiovascular event (adjusted odds ratio, 95% confidence interval 1.89, 1.10 to 3.25) compared with patients with <33% of calcium measurements outside the range. Likewise, patients with any serum phosphate measurements above 0.81 to 1.45 mmol/L (2.5 to 4.5 mg/100 ml) had 3.3-fold higher odds (3.26; 1.24 to 8.58), and those with any calcium-phosphate product measurements above 4.40 mmol2/L2 (55 mg2/dL2) had 4.8-fold higher odds of a cardiovascular event (95% confidence interval 1.36 to 16.81) compared with patients with no measurements above these ranges. In adult patients with chronic hypoparathyroidism, a cardiovascular event was more likely in those with a higher proportion of albumin-corrected serum calcium measurements outside 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) or any serum phosphate and any calcium-phosphate product measurements above the normal population range.

Renin-Angiotensin System-Modifying Antihypertensive Drugs Can Reduce the Risk of Cardiovascular Complications in Lupus: A Retrospective Cohort Study

BackgroundPatients with systemic lupus erythematosus have a higher incidence of cardiovascular disease than the general population. Antihypertensive drugs that modify the renin-angiotensin system (RAS) are used to protect renal function in lupus nephritis and may also have extrarenal effects that lower cardiovascular disease risk due to their anti-inflammatory properties. In this study, we compared the effects of RAS vs non-RAS antihypertensive drugs on cardiovascular disease incidence in patients with lupus. MethodsUsing a medical insurance claims dataset, 220,168 patients with lupus were identified, of which 31,647 patients (4018 patients prescribed RAS drugs, 27,629 patients prescribed non-RAS drugs) were eligible for the study. Patients had a mean age of 46.1 years, were 93.0% female, and healthy (96.9% Charlson Comorbidity Index score 0-4). Patients in the 2 drug groups were propensity score matched using demographic data, risk factors, and comorbidities. ResultsUse of RAS vs non-RAS drugs lowered the relative risk (RR) of diagnosis of cardiovascular disease (RR 0.80; 95% confidence interval [CI], 0.74-0.87), which was more pronounced after propensity score matching (RR 0.62; 95% CI, 0.57-0.68). The decreased risk in cardiovascular disease occurred regardless of lupus nephritis status (with lupus nephritis: RR 0.51; 95% CI, 0.39-0.65; without lupus nephritis: RR 0.65; 95% CI, 0.59-0.72). RAS-modifying therapies significantly increased cardiovascular disease-free survival probability over a 5-year period (86.0% vs 78.3% probability). ConclusionsRAS-modifying drugs reduced the risk of cardiovascular disease in patients with systemic lupus erythematosus in this dataset. These findings have the potential to impact clinical decision-making with regards to hypertension management in patients with lupus.

Effects of fetal famine exposure on the cardiovascular disease risk in the metabolic syndrome individuals

BackgroundPatients with metabolic syndrome (MS) have a higher incidence of cardiovascular disease (CVD), but the possible mechanisms are not fully understood and further exploration of the possible factors influencing the high incidence of CVD in patients with MS is still needed.ObjectivesThis study aims to examine the association between fetal famine exposure and the risk of CVD in adulthood with MS.MethodsOf 13,744 MS patients free of CVD selected from the Kailuan Study in 2006 (referred as the baseline survey) were included in the study. China suffered a severe famine from 1959 to 1962, so the participants born during this period were classified as the uterine famine exposed group. All patients were born between January 1, 1949, and December 31, 1974. Based on the date of birth, all patients were divided into the no-exposed group (born between January 1, 1963, and December 31, 1974), uterine famine exposed group (born between January 1, 1959 and December 31, 1962), and childhood famine exposed group (born between January 1, 1949 and December 31, 1958). After following up to December 31, 2019, the weighted Cox regression analysis model was used to calculate the effect of early life famine exposure in MS individuals on the risk of CVD in adulthood.ResultsDuring the 12.12 years of follow-up, the incidence of CVD was 5.87%, 10.13%, and 10.90% in the no-exposed group, uterine famine exposed group, and childhood famine exposed group, respectively. Compared with participants in the no-exposed group, the CVD risk and stroke risk increased in participants in the uterine famine exposed group (for CVD, HR: 1.32, 95% CI 1.04–1.67; for stroke, HR:1.37, 95% CI 1.05–1.79), but not in childhood famine exposed group. However, the increased CVD risks were only observed in females or smokers. No increased MI risks were observed for participants in the uterine famine exposed group or childhood famine exposed group.ConclusionsOur findings suggested that exposure to famine during uterine life might increase the risk of CVD in adulthood in participants with MS.

Statin treatment and prevalent CVD influence the association between PCSK9 and incident CVD in patients with moderately decreased kidney function: Results from the GCKD study

Background and Aims : Dyslipidemia contributes to the pronounced interconnection between chronic kidney disease (CKD) and cardiovascular disease (CVD). Discovery of the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) led to the development of PCSK9 inhibitors that effectively lower LDL-cholesterol concentrations. Few studies with contradicting results have investigated the association between PCSK9 serum concentrations and cardiovascular outcomes in CKD patients.

HDL, heart disease, and the lung

HDL, heart disease, and the lung

A Prediction Model of Incident Cardiovascular Disease in Patients with Sleep-Disordered Breathing.

(1) Purpose: this study proposes a method of prediction of cardiovascular diseases (CVDs) that can develop within ten years in patients with sleep-disordered breathing (SDB). (2) Methods: For the design and evaluation of the algorithm, the Sleep Heart Health Study (SHHS) data from the 3367 participants were divided into a training set, validation set, and test set in the ratio of 5:3:2. From the data during a baseline period when patients did not have any CVD, we extracted 18 features from electrography (ECG) based on signal processing methods, 30 ECG features based on artificial intelligence (AI), ten clinical risk factors for CVD. We trained the model and evaluated it by using CVD outcomes result, monitored in follow-ups. The optimal feature vectors were selected through statistical analysis and support vector machine recursive feature elimination (SVM-RFE) of the extracted feature vectors. Features based on AI, a novel proposal from this study, showed excellent performance out of all selected feature vectors. In addition, new parameters based on AI were possibly meaningful predictors for CVD, when used in addition to the predictors for CVD that are already known. The selected features were used as inputs to the prediction model based on SVM for CVD, determining the development of CVD-free, coronary heart disease (CHD), heart failure (HF), or stroke within ten years. (3) Results: As a result, the respective recall and precision values were 82.9% and 87.5% for CVD-free; 71.9% and 63.8% for CVD; 57.2% and 55.4% for CHD; 52.6% and 40.8% for HF; 52.4% and 44.6% for stroke. The F1-score between CVD and CVD-free was 76.5%, and it was 59.1% in class four. (4) Conclusion: In conclusion, our results confirm the excellence of the prediction model for CVD in patients with SDB and verify the possibility of prediction within ten years of the CVDs that may occur in patients with SDB.

Association of ANGPTL3 polymorphisms with high-density lipoprotein cholesterol uptake capacity in patients with cardiovascular disease.

IntroductionPrevious studies have shown the importance of angiopoietin‐like 3 (ANGPTL3) as a modulator of lipid profiles. Cholesterol uptake capacity (CUC) is one means for assessing high‐density lipoprotein (HDL) functionality. This study for the first time has investigated the relationship between genetic ANGPTL3 polymorphism and CUC in patients with cardiovascular disease.MethodsFive hundred three subjects comprising 350 healthy subjects and 153 individuals who developed a cardiovascular disease (CVD) event during follow‐up were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. A modified CUC method was used to determine the CUC of serum samples. Applied amplification refractory mutation system PCR was performed for ANGPTL3 variants genotyping including: rs10789117, rs1748195, and rs11207997. Sanger sequencing was applied to confirm the genotypes.ResultsThe results showed that there was a significant relationship between the rs1748195 genotypes and HDL concentration in the CVD group (p = 0.02). Moreover, individuals with a GG genotype of the rs1748195 were associated with a lower risk of CVD (OR = 0.49, 95% CI = 0.24–0.98, p = 0.04) compared with CC genotype in the CUC ≤ 1.7 a.u subgroup. Moreover, the CT genotype of rs11207997 was associated with a lower risk of CVD (OR = 0.74, 95% CI = 0.41–1.3, p = 0.01) compared with CC genotype in CUC > 1.7 a.u subgroup.ConclusionThe results showed that the CT genotype of the rs11207997 variant was associated with a lower risk of incident CVD in patients with higher HDL functionality. As well, the rs1748195 gene variant may contribute to a reduced risk of CVD.

439 Continuous Positive Airway Pressure and Cardiovascular Risk in a Large Clinical Sample of Obstructive Sleep Apnea Patients

Abstract Introduction While studies support the beneficial short-term role of continuous positive airway pressure (CPAP) therapy on cardiometabolic risk in adults with obstructive sleep apnea (OSA), its sustained effect on cardiovascular disease (CVD) risk is unknown. CPAP use data linked to electronic health records (EHR) offer opportunities to understand the role of OSA treatment for preventing CVD. We evaluated the association between CPAP use and CVD incidence in patients referred to a sleep study at a large health system. Methods We included adult patients with available apnea-hypopnea index (AHI) between 01/2018-02/2020 in Kaiser Permanente Southern California. At baseline, eligible participants had &amp;gt;1 year of continuous insurance coverage allowing gaps &amp;lt;90 days and were free of CVD 1 year prior to OSA diagnosis. Participants were distributed into three groups: no OSA (AHI&amp;lt;5), OSA (AHI≥5) with any CPAP use (median[IQR] 2.5[0.7–5.0] h/day) and OSA without evidence of CPAP use. CVD incidence was defined as first occurrence of myocardial infarction, stroke, unstable angina, heart failure or CVD death, based on validated EHR algorithms. We used Cox proportional hazards models to assess the association between OSA with or without CPAP use and CVD incidence, adjusted for baseline age, sex, body mass index, race/ethnicity, Charlson comorbidity index, and use of anti-hypertensives and lipid-lowering medications. Stratified analyses were conducted based on OSA severity. Results We included 11,145 patients without OSA, 13,898 with OSA and CPAP use, and 20,884 patients without CPAP use. Median follow-up was 262 days (IQR=129–409). CVD incidence rates were, respectively, 0.26%, 0.45% and 0.56%. In adjusted models, moderate-severe OSA (AHI≥15) without CPAP use was associated with increased CVD incidence when compared to no OSA (HR=1.71; 95%CI=1.11–2.64; p=0.016). OSA with any CPAP use was associated with lower CVD incidence (HR=0.68; 95%CI=0.50–0.93; p=0.016) when compared to OSA patients with no CPAP use. Stronger effects were observed when restricting the sample to moderate-severe OSA (HR=0.56; 95%CI=0.39–0.81; p=0.002). Conclusion Our analysis in a large observational clinical sample suggests that moderate-severe OSA with no CPAP use is associated with increased CVD incidence. Moreover, OSA with CPAP use was associated with decreased CVD incidence relative to no CPAP use. Support (if any) AASM Foundation (194-SR-18;205-SR-19); AHA (20CDA35310360).

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease.

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MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

BackgroundMid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D.MethodsWe prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP.ResultsA total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]).ConclusionsPatients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

1655-P: Genetic Risk Factors for Incident Cardiovascular Disease in Type 2 Diabetes Patients

Patients with type 2 diabetes (T2D) are at two-fold increased risk of cardiovascular disease (CVD). CVD is the leading cause of T2D morbidity and mortality. The aim of this study was to identify genetic risk factors associated with incident CVD in patients with T2D. We performed survival genome-wide association study (GWAS) with patients with T2D in the UK Biobank (UKBB), Partners HealthCare Biobank (PBB), and Korean Genome and Epidemiology (KoGES) studies. The primary outcome of the study was a composite of myocardial infarction and stroke that occurred at least one year after the diagnosis of T2D. We conducted survival GWAS using ’GWASTools’ R package adjusting for age, and sex. The results of the three cohorts were meta-analyzed using inverse variance weighted method. A total of 19,121 participants were included in the analyses (15,643 from UKBB, 1,161 from PBB and 2,317 from KoGES). The incidence rate of CVD was higher in the hospital-based study of PBB (33.5%) compared to population-based studies of UKBB (9.5%), and KoGES (8.0%). Although there was no genetic association reaching genome-wide significance, there were four genomic loci that had suggestive association evidence for incident CVD with P&amp;lt;1.0x10-6. These include distinct variants in rs113067014 (intergenic) on chromosome 1 (chr1), rs1367414 (intron in PAX3) on chr2, rs11762253 (intron in AC004160.1) on chr7, and rs2837174 (intron in IGSF5) on chr21. When we investigated 184 previously validated coronary artery disease loci, 17 reached nominal significance of P&amp;lt;0.05 with consistent direction of association. A polygenic score (PS) comprised of these 184 variants was significantly associated with risk of CVD in T2D patients (HR 1.20 per s.d. increase in PS, P=6.6x10-16). In summary, we have implemented survival GWAS analysis to investigate genetic risk factors for incident CVD in patients with T2D. However, further increase in sample size is required to identify molecular features leading to increased CVD risk among individuals with T2D. Disclosure S. Kwak: None. J.M. Mercader: None. A. Leong: None. B. Porneala: None. P. Wu: None. J.B. Cole: None. J. Merino: None. K. Park: None. N.H. Cho: None. J. Dupuis: Consultant; Self; Merck Sharp &amp; Dohme Corp. J.C. Florez: Advisory Panel; Self; Doris Duke Charitable Foundation. Other Relationship; Self; Novo Nordisk Inc., Park Street School. J.B. Meigs: Consultant; Self; Quest Diagnostics.

Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. After a median follow-up time of 5.2years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

Incident cardiovascular disease in patients diagnosed with multiple sclerosis: A multi-database study

BackgroundRecent data on rates of cardiovascular disease (CVD) in patients after MS diagnosis are sparse. ObjectiveTo describe incident CVD in MS patients after diagnosis compared with a matched non-MS population. MethodsWe conducted a matched cohort study in two separate electronic medical databases, the United States Department of Defense military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD. The study population included all patients with a first recorded diagnosis of MS and no history of CVD or selected measurable comorbidities associated with CVD and matched non-MS patients who were also free of CVD and the CVD associated comorbidities. We identified incident CVD outcomes first recorded after the MS diagnosis / matched date and calculated incidence rates and incidence rate ratios by type of CVD. ResultsRates of venous thromboembolism and peripheral vascular disease were 2-fold higher among MS than non-MS patients in both databases and the risk of myocardial infarction was 2.5 times higher among female MS patients compared with non-MS females in both databases. Other CVD outcomes were not consistent between databases. ConclusionMS patients in the UK and the US have increased risk of venous thromboembolism and peripheral vascular disease. The risk of myocardial infarction is increased among female MS patients.