Abstract 3573: Higher Soluble Thrombomodulin is Associated with Risk of Coronary Artery Calcification: Longitudinal Analysis of the Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dhananjay Vaidya ◽  
Mary Cushman ◽  
Paul Holvoet ◽  
Joseph F Polak ◽  
Robyn L McClelland ◽  
...  

Background. A prior cross sectional study reported that higher soluble thrombomodulin (sTM) was associated with subclinical atherosclerosis only in the presence of higher soluble intercellular adhesion molecule-1, sICAM-1. We evaluated this interaction longitudinally with regard to coronary artery calcium (CAC) in the MESA cohort. Methods: MESA is a multi-center longitudinal study with baseline measurements of endothelial biomarkers in a random sample (n=1000) of the baseline cohort. In the random sample, 374 men and 496 women had CT measurement for CAC (Agatston score) at baseline and a median follow-up of 2.9 years. Among those with no baseline CAC (n=490), we estimated the relative risk of detectable CAC at follow-up using general linear models with Gaussian error and robust standard errors. Among those with detectable baseline CAC (n=380), change in CAC on follow-up was modeled using robust regression that down-weights outliers. Models with log(sTM) as predictor were adjusted for follow-up time, sex, ethnicity and baseline age, BMI, smoking, diabetes, systolic blood pressure, total cholesterol, use of BP or lipid-lowering medications and for hormone replacement (HRT) in women in separate models. Interactions between sTM and sICAM-1, sex and ethnicity was assessed. Results: The median [interquartile range] of sTM was 38 [28 to 47] ng/mL for persons with incident detectable CAC, and 30 [23 to 41] ng/mL in those without (rank sum p <0.001). On adjustment, a 2-fold higher sTM at baseline (e.g., from 23 to 46 ng/mL) was associated with a 1.36-fold increased risk of detectable CAC on follow-up (95% CI: 1.03, 1.79, p=0.031). Among those with baseline detectable CAC, the rank correlation between sTM level and change in CAC score was 0.10 (p = 0.042), however, on adjustment, a 2-fold higher sTM was associated with a non-significant 0.86 Agatston units greater CAC change (p = 0.84). Higher sICAM-1 did not modify the association of sTM with CAC incidence (interaction p = 0.15) or change (interaction p = 0.26). There was no significant heterogeneity by sex, or ethnicity, or confounding by HRT in women. Conclusion: High circulating levels of sTM were independently associated with incident calcification of the coronary arteries.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hack-Lyoung Kim ◽  
Jung Pyo Lee ◽  
Nathan Wong ◽  
Woo-Hyun Lim ◽  
Jae-Bin Seo ◽  
...  

AbstractThe role of ST2 in stable coronary artery disease (CAD) has not yet been well defined. This study was performed to investigate baseline serum soluble ST2 (sST2) level can predict clinical outcomes in patients with stable CAD. A total of 388 consecutive patients with suspected CAD (65 years and 63.7% male) in stable condition referred for elective invasive coronary angiography (ICA) was prospectively recruited. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization (90 days after ICA), and ischemic stroke during clinical follow-up was assessed. Most of the patients (88.0%) had significant CAD (stenosis ≥ 50%). During median follow-up of 834 days, there was 29 case of MACE (7.5%). The serum sST2 level was significantly higher in patients with MACE than those without (47.3 versus 30.6 ng/ml, P < 0.001). In multiple Cox regression model, higher sST2 level (≥ 26.8 ng/ml) was an independent predictor of MACE even after controlling potential confounders (hazard ratio, 13.7; 95% confidence interval 1.80–104.60; P = 0.011). The elevated level of baseline sST2 is associated with an increased risk of adverse clinical events in stable CAD patients. Studies with larger sample size are needed to confirm our findings.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francisco Albuquerque ◽  
Pedro de Araújo Gonçalves ◽  
Hugo Marques ◽  
António Ferreira ◽  
Pedro Freitas ◽  
...  

AbstractAnomalous origin of the right coronary artery from the opposite sinus (right-ACAOS) with interarterial course (IAC) has been associated with increased risk of sudden cardiac death (SCD). Widespread use of coronary computed tomography angiography (CCTA) has led to increased recognition of this condition, even among healthy individuals. Our study sought to examine the prevalence, anatomical characteristics, and outcomes of right-ACAOS with IAC in patients undergoing CCTA for suspected coronary artery disease (CAD). We conducted a retrospective analysis of consecutive patients referred for CCTA at one tertiary hospital from January 2012 to December 2020. Patients exhibiting right-ACAOS with IAC were analyzed for cardiac symptoms and mid-term occurrence of first MACE (cardiac death, SCD, non-fatal myocardial infarction (MI) or revascularization of the anomalous vessel). CCTAs were reviewed for anatomical high-risk features and concomitant CAD. Among 10,928 patients referred for CCTA, 28 patients with right-ACAOS with IAC were identified. Mean age was 55 ± 17 years, 64% were male and 11 (39.3%) presented stable cardiac symptoms. Most patients had at least one high risk anatomical feature. During follow-up, there were no cardiac deaths or aborted SCD episodes and only 1 patient underwent surgical revascularization of the anomalous vessel. Right-ACAOS with IAC is an uncommon finding (prevalence of 0.26%). In a contemporary population of predominantly asymptomatic patients who survived this condition well into adulthood, most patients were managed conservatively with a low event rate. Additional studies are needed to support medical follow-up as the preferred option in this setting.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Sridharan Raghavan ◽  
Wenhui G Liu ◽  
P. Michael Ho ◽  
Mary E Plomondon ◽  
Anna E Baron ◽  
...  

Background: Diabetes is a significant risk factor for cardiovascular disease, but optimal glycemic control strategies remain unclear. In particular, trials of intensive glycemic control have highlighted a tension between increased mortality risk and macrovascular benefits. In this study we aimed to assess whether the burden of coronary artery disease (CAD) modifies the association between glycemic control and short-term mortality. Methods: We studied veterans with diabetes who underwent elective cardiac catheterization between 2005 and 2013 in a retrospective analysis of data from the VA Clinical Assessment, Reporting, and Tracking (CART) Program. Primary exposures were time-varying HbA1c over two years of follow-up after index catheterization, categorized as <6%, 6-6.49%, 6.5-6.99%, 7-7.99%, 8-8.99%, and >=9%, and burden of CAD, categorized as no CAD, non-obstructive CAD, or obstructive CAD. Primary outcome was two-year all-cause mortality. A total of 17394 participants had, on average, five HbA1c measurements over two years of follow-up. We used multivariable Cox proportional hazards regression to estimate the association between HbA1c and mortality, adjusting for demographic and clinical covariates and CAD burden, and including a term for interaction between HbA1c and CAD burden. Results: In adjusted models with 6.5 ≤ HbA1c ≤ 6.99% as the reference category, HbA1c < 6% was associated with increased risk of mortality (HR 1.55 [1.25, 1.92]), whereas HbA1c categories above 7% were not. We observed significant interaction between glycemic control and CAD burden (interaction p=0.0005); the increased risk of short-term mortality at HbA1c < 6% was limited to individuals with non-obstructive and obstructive CAD (Figure 1). Conclusions: HbA1c below 6% was associated with increased risk of short-term mortality, but only in individuals with CAD. CAD burden may thus inform individualized diabetes management strategies, specifically treatment de-escalation in individuals with any angiographically-defined CAD.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Binh An P Phan ◽  
Bernard Weigel ◽  
Yifei Ma ◽  
Rebecca Scherzer ◽  
Danny Li ◽  
...  

Background: While HIV infection is associated with increased risk of ASCVD (atherosclerotic cardiovascular disease), it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. The purpose of our study was to compare the 2013 ACC/AHA and 2004 ATP III recommendations in a HIV population, and to evaluate associations with carotid artery intima-media thickness (CIMT) and plaque. Methods: We used ultrasound to measure CIMT at baseline and 3 years later in 352 HIV-infected adults with no ASCVD and not on statins. Plaque was defined as IMT > 1.5 mm. We compared 2013 ACC/AHA and 2004 ATP III recommendations, and evaluated associations with CIMT and plaque. Results: At baseline, the median age was 43 (IQR 39-49), 85% were male, 74% were on antiretroviral medication, and 50% had plaque. At follow-up, the median IMT progression was 0.052 mm/yr, and 66% had plaque. The 2013 guideline was more likely to recommend statins compared with the 2004 guideline, both overall (26% vs. 14%, p<.001), in those with plaque (32% vs. 17%, p=.0002), and in those without plaque (16% vs. 7%, p=.025). In unadjusted linear regression, the 2004 and 2013 risk score were strongly associated with CIMT (0.01 mm per 10% increase in risk, p<.001) and with CIMT progression (0.01 mm/yr per 10% increase in risk, p<.001). In multivariate analysis, older age, higher LDL-C, pack-years of smoking, and history of opportunistic infection were associated with baseline plaque. Conclusions: While the 2013 ACC/AHA guideline recommended statins to a greater number of HIV-infected adults compared to the 2004 ATP III guideline, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Both the 2004 and 2013 guidelines predicted higher levels of baseline CIMT and faster progression. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased ASCVD risk and may benefit from statins.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Joost Besseling ◽  
Gerard K Hovingh ◽  
John J Kastelein ◽  
Barbara A Hutten

Introduction: Heterozygous familial hypercholesterolemia (heFH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary artery disease (CAD) and death. Reduction of CAD and mortality by statins has not been properly quantified in heFH. The aim of the current study is to determine the effect of statins on CAD and mortality in heFH. Methods: All adult heFH patients identified by the Dutch FH screening program between 1994 and 2014 and registered in the PHARMO Database Network were eligible. Of these patients we obtained hospital, pharmacy (in- and outpatient), and mortality records in the period between 1995 and 2015. The effect of statins (time-varying) on CAD and all-cause mortality was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, antihypertensive and antidiabetic medication (all time-varying). Furthermore, we used inverse probability for treatment weighting (IPTW) to account for differences between statin-treated and untreated patients regarding history of CAD before follow-up, age at start of follow-up and age of screening, as well as body mass index, LDL-C and triglycerides. Results: Of the 25,479 identified heFH patients, 11,021 gave informed consent to obtain their medical records, of whom 2,447 could be retrieved. We excluded 766 patients younger than 18. The remaining 1,681 heFH patients comprised our study population and these had very similar characteristics as compared to the 23,798 excluded FH patients, e.g. mean (SD) LDL-C levels were 214 (74) vs. 203 (77) mg/dL. Among 1,151 statin users, there were 133 CAD events and 15 deaths during 10,115 statin treated person-years, compared to 17 CAD events and 9 deaths during 4,965 person-years in 530 never statin users (combined rate: 14.6 vs. 5.2, respectively, p<0.001). After applying IPTW to account for indication bias and correcting for use of other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.61 (0.40 - 0.93). Conclusions: In heFH patients, statins lower the risk for CAD and mortality by 39%.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Andrew P DeFilippis ◽  
Holly J Kramer ◽  
Ronit Katz ◽  
Nathan Wong ◽  
Alain Bertoni ◽  
...  

Background: Microalbuminuria (MA) is associated with an increased risk of cardiovascular disease (CVD) but the mechanism by which microalbuminuria imparts this increased risk is not known. In this study we assessed the relationship between MA and the development and progression of atherosclerosis by measuring the incidence of new CAC and the progression of existing CAC in individuals free of clinical CVD. Methods : The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study of 6,814 participants free of clinical CVD at entry who underwent assessment of coronary artery calcification (CAC) by computerized tomography at baseline. Overall, 6,775 individuals had data available on urinary albumin creatinine ratio (UACR); 1,109 individuals were excluded for missing data or macroalbuminuria (UACR≥300 mg/g). Incident CAC was defined as detectable CAC at follow-up among those with CAC=0 at baseline, and absolute CAC score change among those with CAC>0 at baseline. Relative risk (RR) regression adjusted for covariates; and multivariable adjusted median regression was employed to assess the independent relationship of MA with CAC incidence and progression. Results : Of the 5,666 subjects (mean age 62±10 years, 48% males), baseline MA was seen in 424 (7%) participants, who were more likely to have CAC compared to those with normal UACR (62% vs. 48%, p<0.0001). During a mean follow-up of 2.4±0.8 years, those with MA were more likely to develop CAC (28% vs. 15%, p<0.0001) and they had a higher absolute median increase in CAC (47 vs. 29 Agatston Units, p<0.0001). After adjustment for age, gender, ethnicity, site, follow-up duration, diabetes, hypertension, smoking, family history of heart attack, total cholesterol, lipid lowering medications and body mass index; MA was associated with incident CAC (RR 1.65; 95%CI 1.41–2.48) among those with CAC=0 at baseline. Among those with CAC>0 at baseline, MA was associated with a median increase in CAC of 7.93 (95%CI 0.38 –15.47) Agatston Units in multivariable adjusted analyses (variables noted above). Conclusion : MA is independently associated with development of incident CAC and progression of CAC in an asymptomatic multi-ethnic population, and may in part explain its associated increased risk of CVD.


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Laura F Defina ◽  
Nina B Radford ◽  
David Leonard ◽  
Stephen W Farrell ◽  
Andjelka Pavlovic ◽  
...  

Introduction: Recent studies have suggested that extreme levels of physical activity (endurance athletes) are associated with subclinical atherosclerosis as well as increased mortality. The safety of continuing high levels of physical activity is uncertain once coronary artery calcification (CAC) is discovered. Hypothesis: We hypothesized that men performing &ge3000 MET·minutes/week of physical activity would have greater all-cause and cardiovascular (CV) mortality compared to those with &lt1500 or 1500-&lt3000 MET·minutes/week of physical activity and that mortality risk would be greater in those with CAC&ge100 compared to &lt100 Agatston units. Methods: The cohort studied included 16,109 men without prevalent CV disease who reported physical activity levels and underwent EBT or MDCT scan. Physical activity was categorized into &ge3000 (n=1,266), 1500-3000 (n=3,027), and &lt1500 (n=11,816) MET·minutes/week. CAC scanning included EBT scans (1997-2007) or MDCT scans (2007-2013), and CAC score was categorized into &ge100 (n=3,547) and &lt100 (n=12,562) Agatston units. We fit separate proportional hazards regression models to follow-up times for all-cause and CV mortality. The models included all combinations of CAC and physical activity categories and were adjusted for baseline age, smoking, BMI, cholesterol, HDLc, and systolic blood pressure. Results: The average age of participants at baseline was 51.3±8.3 years. Men with the highest activity level had a lower BMI and higher HDLc. After an average follow-up of 8.9 years, there were 329 all-cause and 60 CV deaths, including 174 all-cause and 38 CV deaths in those with CAC&ge100. The sample had 80% power to detect all-cause mortality hazard ratios &ge 1.9 and 1.8 for physical activity &ge3000 versus &lt1500 in those with CAC&lt100 and &ge100, respectively. The corresponding minimum detectable CV mortality hazard ratios were 3.5 and 2.8. Comparing physical activity &ge3000 to &lt1500 in those with CAC&ge100, the hazard ratios (95% CI) were 0.9 (0.5, 1.5) for all-cause mortality and 0.9 (0.3, 3.1) for CV mortality. Hazard ratios were similar when comparing physical activity &ge3000 to 1500-&lt3000 in those with CAC &ge100. Finally, when comparing physical activity categories, there was no evidence that hazard ratios varied by CAC category, p&gt0.7. Conclusions: This sample offers no evidence that levels of activity &ge3000 MET·minutes/week are associated with increased all-cause or CV mortality compared to those with &lt1500 or 1500- &lt3000 MET·minutes/week, regardless of CAC level.


2020 ◽  
Vol 30 (5) ◽  
pp. 685-690
Author(s):  
Tomas Andri Axelsson ◽  
Jonas A Adalsteinsson ◽  
Linda O Arnadottir ◽  
Dadi Helgason ◽  
Hera Johannesdottir ◽  
...  

Abstract OBJECTIVES Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications. METHODS This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes. RESULTS Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27–4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P &lt; 0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P &lt; 0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53–2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23–1.75). CONCLUSIONS Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up.


2019 ◽  
Vol 121 (4) ◽  
pp. 461-468 ◽  
Author(s):  
Tian Hu ◽  
David R. Jacobs ◽  
Lydia A. Bazzano ◽  
Alain G. Bertoni ◽  
Lyn M. Steffen

AbstractThe evidence linking low-carbohydrate diets (LCD) to CVD is controversial, and results from epidemiological studies are inconsistent. We aimed to assess the relationship between LCD patterns and coronary artery Ca (CAC) scores from computed tomography in the Multi-Ethnic Study of Atherosclerosis cohort. Our sample included 5614 men and women free of clinical CVD at baseline (2000–2002), who had a FFQ, a baseline measure and ≥1 measure of CAC during follow-up. We excluded those with implausible energy intake or daily physical activity. The overall, animal-based and plant-based LCD scores were calculated based on intakes of macronutrients. Relative risk regression and robust regression models were used to examine the cross-sectional and longitudinal relationship between LCD score quintile and CAC outcomes, after adjustment for multiple cardiovascular risk factors. The mean age of participants was 63 years. The median intakes of total carbohydrate, fat and protein were 53·7, 30·5 and 15·6 % energy/d, respectively. Among 2892 participants with zero CAC scores at baseline, 264 developed positive scores during 2·4-year follow-up (11–59 months). Among those with positive scores at baseline, the median increase in CAC was 47 units over the course of follow-up. The overall, the animal-based and the plant-based LCD scores were not associated with CAC prevalence, incidence and progression. In conclusion, diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Niloofar Barzegar ◽  
Maryam Tohidi ◽  
Mitra Hasheminia ◽  
Fereidoun Azizi ◽  
Farzad Hadaegh

Abstract Background To investigate whether the Triglyceride-Glucose index (TyG-index) is associated with increased risk of cardiovascular diseases (CVD)/coronary heart disease (CHD). Methods A total of 7521 Iranians aged ≥ 30 years (male = 3367) were included in the study. Multivariate Cox regression analyses (adjusted for age, gender, waist circumference, body mass index, educational level, smoking status, physical activity, family history of CVD, type 2 diabetes, hypertension, low and high density lipoprotein cholesterol, and lipid lowering drugs) were used to assess the risk of incident CVD/CHD across quintiles and for 1-standard deviation (SD) increase in the TyG-index. The cut off point for TyG-index was assessed by the minimum value of $$\sqrt {\left( {1 - sensitivity} \right)^{2} + \left( {1 - specificity} \right)^{2} }$$ 1 - s e n s i t i v i t y 2 + 1 - s p e c i f i c i t y 2 . We also examined the added value of the TyG-index in addition to the Framingham risk score when predicting CVD. Results During follow-up, 1084 cases of CVD (male = 634) were recorded. We found a significant trend of TyG-index for incident CVD/CHD in multivariate analysis (both Ps for tend ≤ 0.002). Moreover, a 1-SD increase in TyG-index was associated with significant risk of CVD/CHD in multivariate analysis [1.16 (1.07–1.25) and 1.19 (1.10–1.29), respectively]. The cut-off value of TyG-index for incident CVD was 9.03 (59.2% sensitivity and 63.2% specificity); the corresponding value of TyG-index for incident CHD was 9.03 (60.0% sensitivity and 62.8% specificity), respectively. Although no interaction was found between gender and TyG-index for CVD/CHD in multivariate analysis (both Ps for interaction > 0.085), the significant trend of TyG-index was observed only among females for incident CVD (P = 0.035). A significant interaction was found between age groups (i.e. ≥ 60 vs < 60 years) and TyG-index for CVD outcomes in the multivariate model (P-value for interaction = 0.046). Accordingly, a significant association between the TyG-index and outcomes was found only among the younger age group. Among the population aged < 60 the addition of TyG-index to the Framingham risk score (FRS) did not show improvement in the predictive ability of the FRS, using integrated discrimination improvement. Conclusion The TyG-index is significantly associated with increased risk of CVD/CHD incidence; this issue was more prominent among the younger population. However, adding TyG-index to FRS does not provide better risk prediction for CVD.


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