scholarly journals Disease burden of subsequent events among patients with atherosclerotic cardiovascular disease in Taiwan

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W.J Chen ◽  
C.Y Hsu ◽  
H.J Lin ◽  
H.M Chen ◽  
W.J Chen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Disease Burden ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
Primary Event ◽  
Readmission Rates ◽  
Sequence Of Events ◽  
Subsequent Event ◽  
New Onset

Abstract Background/Introduction Patients with a history of cardiovascular disease are considered at high risk for cardiovascular (CV) events. Existing studies have indicated that a high proportion of patients developed secondary or tertiary atherosclerotic cardiovascular disease (ASCVD) events within a relatively short period of time. However, the whole picture regarding when and how these subsequent CV events occur is not well understood, particularly in Asia. Purpose To estimate the incidences, characteristics and mortality of subsequent ASCVD events among those with new-onset ASCVD events (index events). Methods We utilized National Health Insurance Research Database in Taiwan to identify patients with new-onset ASCVD events (index events), and further categorized them into those with incident coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD) during 2012–2014. Re-admission due to ASCVD after the index event, defined as subsequent ASCVD event, was our main outcome of interest. All subsequent ASCVD events within 3-year period after the index ASCVD events were identified. Particularly, we intended to sequentially identify first and second subsequent ASCVD events. Descriptive statistics regarding proportion of developing subsequent ASCVD events as well as the type of subsequent ASCVD events were estimated. We also used Kaplan-Meier method to estimate crude survival curve of all-cause mortality following each subsequent ASCVD event. Results We identified 97,321, 120,914 and 14,794 patients with new-onset CHD, CBVD and PAD, respectively. The proportion of developing subsequent events increased with sequence of events occurred (for the first three subsequent event, the proportions of developing subsequent event were: 22.5, 25.6 and 30.9% for CHD, 21.0, 26.2 and 32.4% for CBVD, and 40.2, 41.4 and 43.6% for PAD). The majority of patients had the same type of ASCVD for their subsequent events to the primary event (proportions of having the same ASCVD type of subsequent event to the primary event ranged: 66–81% for CHD, 80–84% for CBVD, and 76–78% for PAD). The 1-year readmission rates increased if patients encountered more subsequent events. Among patients with new-onset CHD, the 1-year readmission rates following new-onset events, first subsequent events and second subsequent events were 43.1%, 47.6% and 55.3%, respectively. More subsequent events also worsened the survival. The 1-year survival rates following new-onset CHD events, first subsequent events and second subsequent events were 85.9%, 84.3% and 79.8%, respectively. Similar trend was observed for CBVD and PAD patients as well. Conclusions Compared with new-onset ASCVD events, subsequent ASCVD events posed a heavier disease burden in terms of readmission and mortality. These results highlighted the importance of prevention of secondary or tertiary ASCVD events. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Taiwan Limited

Low-density lipoprotein cholesterol goal attainment and treatment patterns in a cohort of >143,000 patients with atherosclerotic cardiovascular disease in Ontario, Canada

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fairbairn ◽  
P Oh ◽  
R Goeree ◽  
R.M Rogoza ◽  
M Packalen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Goal Attainment ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Data Repository ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Abstract Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment (<2.0 mmol/L or 50% reduction from index LDL-C) and analysed by LLT and by index event type. Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score >2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.

Arterial calcification in the prediction of atherosclerotic cardiovascular disease among women and men

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.E Van Der Toorn ◽  
D Bos ◽  
B Arshi ◽  
M.K Ikram ◽  
M.W Vernooij ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
The Netherlands ◽  
Arterial Calcification ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Intermediate Risk ◽  
C Statistic ◽  
Ascvd Risk ◽  
Risk Categories

Abstract Background The Coronary Artery Calcium (CAC) Score has emerged as a valuable tool in atherosclerotic cardiovascular disease (ASCVD) risk stratification. However, data on the relevance of arterial calcification in different vascular territories for ASCVD risk prediction is lacking. Purpose First, to assess the sex-specific distribution of arterial calcification in different vessel beds across ASCVD risk categories. Second, to determine the added value of arterial calcification in different vascular territories for ASCVD risk prediction. Methods From a large population-based study, 2,139 participants (mean age 69 years, 55% women) underwent non-contrast computed tomography to quantify CAC, aortic arch calcification (AAC), extracranial- (ECAC) and intracranial carotid artery calcification (ICAC), and vertebrobasilar artery calcification (VBAC). The outcome measure, incident ASCVD, composed of fatal and nonfatal myocardial infarction (MI), other coronary heart disease (CHD) mortality, and stroke. We fitted sex-specific prediction models according to the Pooled Cohort Equations (PCE), and categorized participants into low- (<5%), borderline- (5% to 7.5%), intermediate- (7.5% to 20%), and high ASCVD risk (≥20%), based on the American College of Cardiology (ACC) and American Heart Association (AHA) guideline. Subsequently, we determined the distribution of calcifications in different vascular territories across the risk categories. Next, we extended the PCE prediction model with calcification volumes and calculated the c-statistic and the net reclassification improvement for events (NRIe) and non-events (NRIne). Results The median follow-up for ASCVD was 9.3 years. Among women, 38% was classified as low-risk, 19% as borderline risk, 31% as intermediate risk, and 12% as high risk. Among men, 2% was classified as low-risk, 10% as borderline risk, 60% as intermediate risk, and 28% as high risk. With increasing risk of ASCVD, a larger burden of calcification was observed. In women, simultaneously adding calcification volumes in all vessel beds led to the largest increase in c statistic (from 0.71 to 0.75) for the prediction of ASCVD and the most beneficial reclassification (NRIe: 11%, NRIne: 2%). Among men, the addition of CAC alone most substantially improved the prediction of ASCVD (c statistic improved from 0.65 to 0.68, NRIe and NRIne were 4% and 14%, respectively). Conclusions Our findings suggest a potential role for comprehensive assessment of calcification in different vessel beds for ASCVD risk stratification in particular among women. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Rotterdam Study is supported by Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; European Commission; and the Municipality of Rotterdam. Dr. Kavousi is supported by the VENI grant (91616079) from ZonMw. Dr. Bos was supported by a fellowship of the BrightFocus Foundation (A2017424F). Oscar L. Rueda-Ochoa receives a scholarship from COLCIENCIAS-Colombia and support from Universidad Industrial de Santander,UIS-Colombia. None of the funders had any role in study design; study conduct; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article.

Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Francesca Watson ◽  
Maddalena Ardissino ◽  
Ravi J Amin ◽  
Chanpreet Arhi ◽  
Peter Collins ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Disease Burden ◽  
Atherosclerotic Cardiovascular Disease ◽  
Obese Patients ◽  
Matched Cohort ◽  
All Cause Mortality

Introduction: Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM. Hypothesis: Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM. Methods: A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually. Results: Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls. Conclusions: In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.

scholarly journals Elevated Triglycerides (≥150 mg/dL) and High Triglycerides (200–499 mg/dL) Are Significant Predictors of Hospitalization for New-Onset Kidney Disease: A Real-World Analysis of High-Risk Statin-Treated Patients

2019 ◽  
Vol 9 (6) ◽  
pp. 400-407 ◽  
Author(s):  
Peter P. Toth ◽  
Sephy Philip ◽  
Michael Hull ◽  
Craig Granowitz
Keyword(s):  
High Risk ◽  
Kidney Disease ◽  
Real World ◽  
Density Lipoprotein ◽  
Cox Proportional Hazards Model ◽  
Lipoprotein Cholesterol ◽  
Administrative Claims ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
New Onset

Background: Dyslipidemia in kidney disease (KD) involves increased levels of triglycerides (TG) and TG-rich lipoproteins, with only minor changes in low-density lipoprotein cholesterol. The increasing prevalence of diabetic KD and the shared atherogenic lipid profile between KD and diabetes underscore the importance of understanding dyslipidemia in these patients. Previous studies suggest an association between elevated TG and new-onset KD. Additional data are needed to better define the relationship between hypertriglyceridemia and new-onset KD. Objective: To evaluate the real-world impact of elevated and high TG on risk of KD in high-risk statin-treated patients. Methods: This retrospective administrative claims analysis of the Optum Research Database included statin-treated patients (age ≥45 years) with diabetes and/or atherosclerotic cardiovascular disease who were followed for ≥6 months. Cohorts included patients with elevated TG (≥150 mg/dL; n = 27,471) or high TG (200–499 mg/dL; subgroup of elevated TG cohort; n = 13,411), and a comparator cohort (TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL; n = 32,506). The probability of hospitalization for new-onset KD was calculated post hoc from multivariate analyses controlled for patient characteristics and comorbidities using a Cox proportional hazards model. Results: The rate of hospitalization for new-onset KD was 31% higher in the elevated-TG cohort (hazard ratio [HR], 1.311; 95% confidence interval [CI], 1.228–1.401; p < 0.001) and 45% higher in the high-TG cohort (HR, 1.451; 95% CI, 1.339–1.572; p < 0.001) compared with the respective comparator cohorts. Conclusions: In a real-world analysis of statin-treated patients with high cardiovascular risk, both elevated TG (≥150 mg/dL) and high TG (200–499 mg/dL) were significant predictors of hospitalization for new-onset KD, identifying hypertriglyceridemia as a potential KD risk factor.

scholarly journals Diabetes, Heart Failure, and COVID-19: An Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Carleigh Hebbard ◽  
Brooke Lee ◽  
Rajesh Katare ◽  
Venkata Naga Srikanth Garikipati
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Heart Disease ◽  
Disease Burden ◽  
Clinical Findings ◽  
Current Data ◽  
Future Research ◽  
The Novel ◽  
Research Areas ◽  
New Onset

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the WHO in March 2020. As of August 2021, more than 220 countries have been affected, accounting for 211,844,613 confirmed cases and 4,432,802 deaths worldwide. A new delta variant wave is sweeping through the globe. While previous reports consistently have demonstrated worse prognoses for patients with existing cardiovascular disease than for those without, new studies are showing a possible link between SARS-CoV-2 infection and an increased incidence of new-onset heart disease and diabetes, regardless of disease severity. If this trend is true, with hundreds of millions infected, the disease burden could portend a potentially troubling increase in heart disease and diabetes in the future. Focusing on heart failure in this review, we discuss the current data at the intersection of COVID, heart failure, and diabetes, from clinical findings to potential mechanisms of how SARS-CoV-2 infection could increase the incidence of those pathologies. Additionally, we posit questions for future research areas regarding the significance for patient care.

scholarly journals Real-world analyses of patients with elevated atherosclerotic cardiovascular disease risk from the Optum Research Database

2020 ◽  
Author(s):  
Peter P Toth ◽  
Michael Hull ◽  
Craig Granowitz ◽  
Sephy Philip
Keyword(s):  
Cardiovascular Disease ◽  
Real World ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Healthcare Resource Utilization ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
Icosapent Ethyl ◽  
Atherosclerotic Cardiovascular Disease Risk ◽  
Peripheral Arterial

More than 56 million Americans have hypertriglyceridemia, including over 12 million statin-treated individuals. However, the contribution of elevated and high triglyceride levels to cardiovascular disease and death has not been extensively studied using real-world analyses. We review recent analyses of the Optum Research Database, which included patients aged ≥45 years with diabetes and/or atherosclerotic cardiovascular disease and on statin therapy. Triglyceride levels ≥150 and 200–499 mg/dl were significantly associated with a 25.8 and 34.9% increased relative risk of cardiovascular events, respectively, versus patients with triglyceride levels <150 mg/dl. In addition, hypertriglyceridemia predicted peripheral arterial revascularization, new heart failure diagnosis and new-onset renal disease. Increased triglyceride levels were also significantly associated with increased healthcare resource utilization and costs. Interventions such as icosapent ethyl reduce triglycerides and associated cardiovascular disease risk.

Long-term safety and efficacy of bempedoic acid in patients at high risk of atherosclerotic cardiovascular disease: results from the CLEAR Harmony open-label extension study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.M Ballantyne ◽  
M Banach ◽  
H.E Bays ◽  
A.L Catapano ◽  
U Laufs ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cumulative Exposure ◽  
Lipid Lowering ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Therapeutic Area ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Extension

Abstract Background Bempedoic acid (BA) is an oral first-in-class, ATP-citrate lyase inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) levels in adults with hypercholesterolemia. In the phase 3 CLEAR Harmony study (NCT02666664, n=2230), BA 180 mg for 52 weeks significantly lowered LDL-C at week 12 compared with placebo and was maintained for 52 weeks in hypercholesterolemic patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) on stable, maximally tolerated statins. Purpose To report long-term safety, tolerability, and efficacy of BA from the CLEAR Harmony open-label extension (OLE) study (NCT03067441). Methods After completing the 52-week placebo-controlled CLEAR Harmony study, patients immediately entered the OLE and received BA for 78 weeks, followed by a 4-week washout period; the potential cumulative exposure to BA was 2.5 years. The primary endpoint was long-term safety of BA in the OLE. Results A total of 1462 patients enrolled in the OLE (BA n=970; placebo n=492 from CLEAR Harmony). At OLE baseline, mean (SD) age was 66.9 (8.7) years, 73.9% were male, 96.3% had ASCVD, 3.7% had HeFH with or without ASCVD, and all were receiving statins (93.5% moderate or high intensity). At baseline of CLEAR Harmony, patients had mean (SD) LDL-C of 102.9 (29.9) mg/dL (BA) and 99.0 (24.2) mg/dL (placebo). The majority of OLE patients (86.2%, n=1260) completed 78 weeks of BA treatment. At week 12 and 78 of OLE treatment, respectively, mean LDL-C lowering from CLEAR Harmony baseline was –14.9% and –14.4%. A total of 1143 patients (78.2%) reported a treatment-emergent adverse event (TEAE), and 299 (20.5%) reported a serious TEAE. TEAEs of special interest, determined by the therapeutic area or prior observations in preclinical or early clinical studies, occurred at similar rates as CLEAR Harmony (creatine kinase elevations, 1.8%; gout, 2.6%; hepatic enzyme elevations, 2.0%; hypoglycemia, 1.2%; muscular disorders, 8.5%; neurocognitive disorders, 0.9%; new onset/worsening diabetes mellitus, 5.5%; renal disorders, 2.8%) with biochemical changes that were stable over the course of the study and approached baseline levels after treatment discontinuation. Overall, 114 patients (7.8%) reported a TEAE leading to discontinuation of BA (most common: myalgia [0.6%], muscle spasm [0.5%]). Conclusion Durable lipid lowering was observed through 78 weeks of BA treatment and patient adherence to BA therapy was high (86.2%). Overall safety during the OLE was similar to results reported in the 52-week-long CLEAR Harmony study and the overall BA phase 3 clinical program, with no new safety findings. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Esperion Therapeutics, Inc., funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Agnella Izzo Matic, PhD, CMPP, and Kelly M Cameron, PhD, CMPP, of JB Ashtin.

scholarly journals Risk of acute atherosclerotic cardiovascular disease in patients with acute and chronic pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-Chin Sung ◽  
Chuen-Chau Chang ◽  
Chao-Shun Lin ◽  
Chun-Chieh Yeh ◽  
Yih-Giun Cherng ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Acute Pancreatitis ◽  
Liver Cirrhosis ◽  
Chronic Pancreatitis ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
Increased Risk ◽  
History Of ◽  
Acute And Chronic Pancreatitis

AbstractThe association between pancreatitis and acute myocardial infarction or stroke remains incompletely understood. This study aimed to evaluate the long-term risk of acute atherosclerotic cardiovascular disease (ASCVD) in people with acute and chronic pancreatitis. Using research database of Taiwan's National Health Insurance, we identified 2678 patients aged ≥ 20 years with newly diagnosed pancreatitis in 2000–2008. A cohort of 10,825 adults without pancreatitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident acute ASCVD was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acute ASCVD associated with pancreatitis were calculated. Compared with the comparison cohort, the adjusted HR of acute ASCVD were 1.76 (95% CI 1.47–2.12) and 3.42 (95% CI 1.69–6.94) for people with acute pancreatitis and chronic pancreatitis, respectively. A history of alcohol-related illness (HR 9.49, 95% CI 3.78–23.8), liver cirrhosis (HR 7.31, 95% CI 1.81–29.5), and diabetes (HR 6.89, 95% CI 2.18–21.8) may worsen the risk of acute ASCVD in patients with chronic pancreatitis. Compared with people had no pancreatitis, patients with acute pancreatitis who had alcohol-related illness (HR 4.66, 95% CI 3.24–6.70), liver cirrhosis (HR 4.44, 95% CI 3.05–6.47), and diabetes (HR 2.61, 95% CI 2.03–3.36) were at increased risk of acute ASCVD. However, the cumulative use of metformin was associated with a reduced risk of acute ASCVD in the acute pancreatitis cohort (HR 0.30, 95% CI 0.17–0.50). Compared with the control group, patients with acute or chronic pancreatitis were more likely to have an increased risk of acute ASCVD, while the use of metformin reduced the risk of acute ASCVD. Our findings warrant a survey and education on acute ASCVD for patients with acute and chronic pancreatitis.

scholarly journals Circulating levels of metabolic biomarkers of site-specific and sex-specific arterial calcification in the multi-cohort BBMRI setting

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Bos ◽  
N.A Van Vliet ◽  
M Beekman ◽  
P.E Slagboom ◽  
M Vernooij ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Proton Nuclear Magnetic Resonance ◽  
Arterial Calcification ◽  
P Value ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Biological Mechanisms ◽  
Site Specific ◽  
Metabolic Biomarkers ◽  
Circulating Levels

Abstract Background/Introduction Increasing evidence shows that greater arterial calcification leads to an elevated risk of atherosclerotic cardiovascular disease. Risk factors and prognosis of arterial calcification seems to vary per site and between women and men. However, the underlying biological mechanisms of site-specific calcification and the associated sex differences are largely unknown. Within the BBMRI framework, we performed a multi-cohort study on the associations of the circulating levels of metabolic biomarkers with arterial calcification at various sites among women and men. Purpose To examine the associations of the circulating levels of metabolic biomarkers with coronary artery (CAC), aortic arch (AAC) and the aortic valve (AVC) calcifications among women and men. Methods We included a total of 1,114 participants from the population-based Rotterdam Study and 390 from the Leiden Longevity Study. Study populations were comparable concerning study characteristics. Blood samples were used to determine a wide range of plasma metabolic biomarkers by proton nuclear magnetic resonance (NMR). Participants underwent non-contrast computed tomography to quantify the volume of CAC, AAC, and AVC. Linear regression modelling adjusted for relevant covariates was used to assess the associations of 166 metabolic biomarkers with CAC, AAC, and AVC. Correction for multiple testing was based on 33 independent metabolic biomarkers (p-value 0.05/33 = 1.5 x 10–3). Results Mean (standard deviation - SD) age was 69.5 (6.8) and 780 (52.0%) of the study population were women. One SD increase in concentration of a1-acid glycoprotein, was associated with a 0.10 SD (standard error (SE) = 0.03) increase in AAC (p-value = 9.5x10–4) in the overall population (Figure 1). When we stratified our analyses based on sex, this association was mainly driven by men [beta (SE) per SD: 0.12 (0.05), p-value = 0.007]. Moreover, an SD increase in acetate was associated with a 0.14 SD (SE = 0.04) decrease in CAC (p-value 1.7x10–4) in women but not in men [beta (SE) per SD: −0.04 (0.03), p-value = 0.22] (Figure 1). Conclusion(s) Higher levels of circulating glycoproteins were associated with increased AAC in men. Moreover, lower levels of circulating acetate were associated with increased CAC in women. These results provide evidence for location-specific differences and sex-specific effects in the underlying biological mechanisms of atherosclerosis. Our findings carry the potential to contribute to the early detection of individuals at increased risk for developing atherosclerotic cardiovascular disease and to a better understanding of disease etiology. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was performed within the framework of the BBMRI Metabolomics Consortium funded by BBMRI-NL, a research infrastructure financed by the Dutch government through Netherlands Organisation for Scientific Research (NWO) (Grant Nos. 184.021.007 and 184033111). MK was supported by VENI grant (91616079) from The Netherlands Organization for Health Research and Development (ZonMw).

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