Coronary Artery Calcification Levels Research Articles

Cerebral white matter hyperintensities indicate severity and progression of coronary artery calcification

Cerebral white matter hyperintensities (WMH) have been associated with subclinical atherosclerosis including coronary artery calcification (CAC). However, previous studies on this association are limited by only cross-sectional analysis. We aimed to explore the relationship between WMH and CAC in elderly individuals both cross-sectionally and longitudinally. The study population consisted of elderly stroke- and dementia-free participants from the community-based Austrian Stroke Prevention Family Study (ASPFS). WMH volume and CAC levels (via Agatston score) were analyzed at baseline and after a 6-year follow-up period. Of 324 study participants (median age: 68 years), 115 underwent follow-up. Baseline WMH volume (median: 4.1 cm3) positively correlated with baseline CAC levels in multivariable analysis correcting for common vascular risk factors (p = 0.010). While baseline CAC levels were not predictive for WMH progression (p = 0.447), baseline WMH volume was associated CAC progression (median Agatston score progression: 27) in multivariable analysis (ß = 66.3 ± 22.3 [per cm3], p = 0.004). Ten of 11 participants (91%) with severe WMH (Fazekas Scale: 3) at baseline showed significant CAC progression > 100 during follow-up. In this community-based cohort of elderly individuals, WMH were associated with CAC and predictive of its progression over a 6-year follow-up. Screening for coronary artery disease might be considered in people with more severe WMH.

Abstract 15267: Differential Effect of Calcium Score on Major Adverse Cardiac Events in Men and Women

Introduction: Coronary artery calcium (CAC) is well-validated for cardiovascular risk stratification. There are well-known gender differences in the presentation, diagnosis, and management of cardiac diseases that have been extensively studied in the past. To date, there have not been extensive studies to look at the differential effect of CAC score on major adverse cardiac events (MACE; defined as death, MI, stroke, or coronary revascularization) amongst men and women. The objective of our study is to look at this aspect. Methods/Results: Data were analyzed on a group of 1,380 patients who had participated in both the Sanford Health Heart Screen Program and the Sanford Health Preemptive Genomic Screening Program. These patients had their heart screen between 2011 and 2021 and their genetic testing between 2018-2022. Patients consented to both forms of screening independently, and the results were analyzed by means of a retrospective review. While other genetic factors were excluded from this study, we separated patients by sex. This sample had 64% female and 36% male. 10% of males had a MACE event and 4.9% of females had a MACE event. Males had higher levels of CAC (M=249.55, SD=550.41) compared to that of females (M=57.97, SD=190.5). The correlation between CAC and MACE was higher for males (r=0.33, p<0.01) than it was for females (r=0.17, p<0.05), Zou’s CI [.06, .26]. Conclusion: Males, overall had a higher level of CAC score compared to females. The correlation between the CAC score and MACE was also higher for males, as compared to females.

PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Prognostic Value of Coronary CT Angiography-derived Fractional Flow Reserve on 3-year Outcomes in Patients with Stable Angina.

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry

BackgroundElevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk. ObjectivesThe authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event. MethodsThe authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors. ResultsThe mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates. ConclusionsPatients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly.

High-Sensitivity Troponins and Subclinical Coronary Atherosclerosis Evaluated by Coronary Calcium Score Among Older Asians Living With Well-Controlled Human Immunodeficiency Virus.

Elevated levels of high-sensitivity cardiac troponin (hs-cTn) are suggestive of myocardial cell injury and coronary artery disease. We explored the association between hs-cTn and subclinical arteriosclerosis using coronary artery calcification (CAC) scoring among 337 virally suppressed patients with human immunodeficiency virus (HIV) who were ≥50 years old and without evidence of known coronary artery disease. Noncontrast cardiac computed tomography and blood sampling for hs-cTn, both subunit I (hs-cTnI) and subunit T (hs-cTnT), were performed. The relationship between CAC (Agatston score) and serum hs-cTn levels was analyzed using Spearman correlation and logistic regression models. The patients, of whom 62% were male, had a median age of 54 years and had been on antiretroviral therapy for a median of 16 years; the CAC score was >0 in 50% of patients and ≥100 in 16%. Both hs-cTn concentrations were positively correlated with the Agatston score, with correlation coefficients of 0.28 and 0.27 (P < .001) for hs-cTnI and hs-cTnT, respectively. hs-cTnI and hs-cTnT concentrations of ≥4 and ≥5.3 pg/mL, respectively, provided the best performance for discriminating patients with Agatston scores ≥100, with a sensitivity and specificity of 76% and 60%, respectively, for hs-cTnI and 70% and 50% for hs-cTnT. In multivariable logistic regression analysis, each log unit increase in hs-cTnI level was independently associated with increased odds of having an Agatston score ≥100 (odds ratio, 2.83 [95% confidence interval, 1.69-4.75]; P <.001). Although not an independent predictor, hs-cTnT was also associated with an increased odds of having an Agatston score ≥100 (odds ratio, 1.58 [95% confidence interval, .92-2.73]; P = .10). Among Asians aged ≥50 years with well-controlled HIV infection and without established cardiovascular disease, 50% had subclinical arteriosclerosis. Increasing hs-cTnI and hs-cTnT concentrations were associated with an increased risk of severe subclinical arteriosclerosis, and hs-cTn may be a potential biomarker to detect severe subclinical arteriosclerosis.

Coronary artery calcium progression and all-cause mortality.

Coronary artery calcium (CAC) has been demonstrated as a noninvasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events. While it has been previously shown that CAC progression predicts all-cause mortality, we sought to quantify this association by examining a large cohort over a follow-up period of 1-22 years. We studied 3260 persons aged 30-89 years referred by their primary physician for CAC measurement, with a follow-up scan at least 12 months from the initial scan. Receiver operator characteristic (ROC) curves assessed a level of annualized CAC progression that predicted all-cause mortality. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios and 95% confidence intervals (CIs) for the association between annualized CAC progression and death after adjusting for relevant cardiovascular risk factors. The average time between scans was 4.7 ± 3.2 years with an additional average of 9.1 ± 4.0 years of follow-up time. The average age of the cohort was 58.1 ± 10.5 years, 70% being male, and 164 deaths occurred. Annualized CAC progression of 20 units optimized sensitivity (58%) and specificity (82%) in ROC curve analysis. Annualized CAC progression of 20 units was significantly associated with mortality while adjusting for age, sex, race, diabetes, hypertension, hyperlipidemia, smoking, baseline CAC level, family history, and time between scans, hazard ratio 1.84 (95% CI, 1.28-2.64) P = 0.001. Annualized CAC progression of greater than 20 units per year significantly predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.

Associations of Whole Blood Zinc Levels with Coronary Artery Calcification and Future Cardiovascular Events in CKD Patients.

This study was conducted to compare the differences of the whole blood zinc concentration in patients with chronic kidney disease (CKD) as compared to healthy controls, and to explore the correlations of the whole blood zinc level with coronary artery calcification (CAC) and cardiovascular event (CVE) in CKD patients. A total of 170 CKD patients and 62 healthy controls were recruited. The whole blood zinc concentration was determined in using atomic absorption spectroscopy (AAS) method. The degrees of CAC were evaluated by Agatston score based on computed tomography (CT). Regular follow-up visits were performed to record the incidence of CVE, and risk factors were analyzed by COX proportional hazard model and Kaplan-Meier survival curve. There were statistically significant lower zinc levels in CKD patients than in healthy population. The prevalence of CAC was 58.82% in CKD patients. Correlation analysis showed that dialysis duration, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), 25-hydroxyvitamin D3 (25(OH)D3), neutrophil-lymphocyte ratio (NLR), total cholesterol (TC), and high-sensitive C-reactive protein (Hs-CRP) were positively correlated with CAC, while albumin (ALB), hemoglobin (Hb), and zinc levels were negatively associated with CAC. Further COX proportional hazard model demonstrated that moderate to severe CAC, NLR, phosphate, 25(OH)D3, iPTH, and high-density lipoprotein (HDL) were associated with an increased risk for CVE, while zinc levels, Hb, and ALB were inversely associated with a reduced risk for CVE. Kaplan-Meier curve showed that low zinc (zinc < 86.62μmol/L) patients and moderate to severe CAC patients had lower survival respectively. Our study found the lower levels of zinc and higher prevalence of CAC in CKD patients; the low zinc is involved in the high incidence rate of moderate to severe CAC and CVE in CKD patients.

Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients.

Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated. In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST). Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time. Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.

Testosterone is positively associated with coronary artery calcium in a low cardiovascular disease risk population.

In industrialized populations, low male testosterone is associated with higher rates of cardiovascular mortality. However, coronary risk factors like obesity impact both testosterone and cardiovascular outcomes. Here, we assess the role of endogenous testosterone on coronary artery calcium in an active subsistence population with relatively low testosterone levels, low cardiovascular risk and low coronary artery calcium scores. In this cross-sectional community-based study, 719 Tsimane forager-horticulturalists in the Bolivian Amazon aged 40+ years underwent computed tomography (49.8% male, mean age 57.6 years). Coronary artery calcium levels were low; 84.5% had no coronary artery calcium. Zero-inflated negative binomial models found testosterone was positively associated with coronary artery calcium for the full sample (Incidence Rate Ratio [IRR] = 1.477, 95% Confidence Interval [CI] 1.001-2.170, P = 0.031), and in a male-only subset (IRR = 1.532, 95% CI 0.993-2.360, P = 0.053). Testosterone was also positively associated with clinically relevant coronary atherosclerosis (calcium >100 Agatston units) in the full sample (Odds Ratio [OR] = 1.984, 95% CI 1.202-3.275, P = 0.007) and when limited to male-only sample (OR = 2.032, 95% CI 1.118-4.816, P = 0.024). Individuals with coronary artery calcium >100 had 20% higher levels of testosterone than those with calcium <100 (t = -3.201, P = 0.007). Among Tsimane, testosterone is positively associated with coronary artery calcium despite generally low normal testosterone levels, minimal atherosclerosis and rare cardiovascular disease (CVD) events. Associations between low testosterone and CVD events in industrialized populations are likely confounded by obesity and other lifestyle factors.

PS-C15-3: CORRELATIONS BETWEEN CORONARY ARTERY DISEASE, CORONARY ARTERY CALCIUM SCORE, AND LIPOPROTEIN(A) LEVEL IN KOREA

Background: Lipoprotein(a) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA). Methods: This was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement within a three-month interval. Coronary angiography and further management were performed according to the physicians decision. Among 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400). Results: No relationship was observed between Lp(a) and CAD and other risk factors for that. There were no differences in the ratio of patients who underwent coronary revascularization and the CAC score according to an Lp(a) level of 50 ml/dL. There was no difference in Lp(a) level at a CAC level of 400. The proportion of patients who underwent coronary intervention was high in the high CAC score group (50.6% vs. 23.7%, p = 0.000). No association was observed between Lp(a) and CAC in the Pearson correlation (0.000, p &lt; 0.998). Conclusion: Correlations between Lp(a) and CAC and between Lp(a) and CAD were not observed in Korean patients. However, a high CAC score was correlated with coronary revascularization.

Subclinical atherosclerosis determined by coronary artery calcium deposition in patients with clinical familial hypercholesterolemia

Background and aimsLimited knowledge exists regarding the association between coronary artery calcium (CAC) deposition in patients with clinical familial hypercholesterolemia (FH) and FH subtypes such as polygenic causes. We studied CAC score in patients with clinical FH and subtypes including polygenic causes of FH compared to healthy controls. MethodsIn a case-control study, we identified potential clinical FH cases registered with an LDL-C >6.7 mmol/l within a nationwide clinical laboratory database on the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. All subjects were aged 18–75 years and without a history of cardiovascular disease. FH mutation testing and genotypes of twelve LDL-C associated single nucleotide polymorphisms were determined using conventional methods in selected individuals. CAC scores were assessed by cardiac CT. Odds ratios obtained using multivariate logistic regression were used as measures of association. ResultsA total of 120 clinical FH patients and 117 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (3%), but a high level of polygenic FH (60%) in those genetically tested (54%). There was a statistically significant association between the CAC score and a diagnosis of clinical FH with the highest observed odds ratio of 5.59 (95% CI 1.65; 18.94, p = 0.006) in those with a CAC score ≥300 compared to those with a CAC of zero. In supplemental analyses, there was a strong association between CAC scores and clinical FH of a polygenic cause. ConclusionWe found a statistically significant association between CAC levels and clinical FH with the highest observed risk estimates among clinical FH cases of a presumed polygenic cause.

Abstract 13660: Lp(a) is Associated With Coronary Artery Calcification in a Population With Exceptionally Low Cardiovascular Disease Risk

Introduction: The Tsimane forager-horticulturalists of Bolivia are highly physically active, carry high infectious disease burdens, and have the lowest reported population levels of coronary artery calcium (CAC), as well as relatively low cholesterol (LDL, HDL, total) levels. In industrialized populations, lipoprotein(a)—Lp(a)— is strongly predictive of coronary artery and aortic valve calcification (AVC). However, these relationships have not been assessed in this non-urban population. Hypothesis: We hypothesize that, despite the very low levels of CAC seen in the Tsimane, Lp(a) is higher in those with CAC and AVC but overall lower in Tsimane compared to a US comparator population (CARDIA). Methods: CAC and AVC were measured by non-contrast cardiac CT in 917 Tsimane (15.5% CAC positive, 21.0% AVC positive). A subset of 98 Individuals with and without CAC or AVC had serum Lp(a) analyzed (median age 63 yrs, range 41-91 yrs, 67% male) using a standard double monoclonal antibody ELISA at the Northwest Lipid Metabolism and Diabetes Research Laboratory (University of Washington). Individuals with CAC and AVC were oversampled (45.9% CAC positive, and 76.7% with AVC; 10% with neither) to ensure statistical power. Results: Overall, Tsimane had significantly lower levels of Lp(a) than CARDIA white males (Tsimane male median 16.5 nmol/L vs US median 19.4 nmol/L; p&lt;0.001) and CARDIA white females (Tsimane female median 11.5 nmol/L vs US median 21.9 nmol/L; p&lt;0.001), despite oversampling Tsimane with CAC and AVC. While Tsimane Lp(a) was low, individuals with CAC had significantly higher Lp(a) (p=0.030) controlling for age, sex, and body fat. Tsimane with no CAC had a median Lp(a) of 12.2 nmol/L, while those with any CAC signal had a median Lp(a) of 17.7 nmol/L. There was no association between AVC and Lp(a). Conclusions: While the Tsimane have lower levels of both CAC and Lp(a) than US adults, Lp(a) is significantly higher in Tsimane with CAC. The absence of association between Lp(a) and AVC may indicate that among the Tsimane, the etiology of AVC may be less tied to Lp(a) than in industrial populations. These results suggest that Lp(a) is associated with arterial calcification even in patients with low overall cardiovascular disease risk.

Prognostic value of FFRCT in patients with stable chest pain – a 3-year follow-up of the ADVANCE-DK registry

Abstract Introduction The short-term safety of using coronary CT angiography (CTA) derived fractional flow reserve (FFRCT) to guide downstream testing after CTA is well documented. Whether the prognostic information provided by FFRCT can be extended to sustained follow-up and to patients with a high degree of coronary artery calcification (CAC) is unknown. Purpose To evaluate the association between FFRCT and clinical outcomes in new onset stable symptomatic patients with coronary stenosis up to 3 years after CTA index testing. Methods Multicenter 3-year follow-up study of 900 patients from the Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care (ADVANCE) registry at three Danish sites, the “ADVANCE-DK Registry”. All patients had at least one ≥30% coronary stenosis by CTA and underwent subsequent core laboratory FFRCT analysis by HeartFlow. The criterium for an abnormal FFRCT test result was an FFRCT value ≤0.80 (2 cm distal to stenosis). High CAC was defined as a CAC score ≥400. The primary endpoint (PE) was a composite of all-cause death and spontaneous myocardial infarction (MI). The secondary endpoint (SE) was a composite of cardiovascular (CV) death and spontaneous MI. Events were adjudicated by an independent clinical committee. Results Patient characteristics are given in Table 1. Coronary stenosis ≥50% was present in 750 (83%) patients. In total 36 patients suffered a PE (all-cause death, n=24; MI, n=12) and 22 an SE (CV death, n=10; MI, n=12). An abnormal vs a normal FFRCT test result was associated with an increased risk of the PE and of the SE both overall and in patients with high CAC; PE (all), 6.6% vs 2.1%, relative risk (RR): 3.1; 95% CI: 1.6–6.3, p&amp;lt;0.001, SE (all), 5.0% vs 0.6%, RR: 8.7; 95% CI: non assessable, p&amp;lt;0.001, PE (high CAC), 9.0% vs 2.2%, RR: 4.1; 85% CI: 1.4–11.8, p=0.001, and SE (high CAC), 6.6% vs 0.5%, RR: 12.0; 95% CI: non assessable, p=0.01, respectively, Figure 1. The observed increased risk in patients with an abnormal vs a normal FFRCT test result persisted after adjustment for degree of stenosis by CCTA (&amp;lt; / ≥50%) and amount of CAC (&amp;lt; / ≥400): PE, adjusted RR: 2.5; 95% CI: 1.2–5.2, p=0.02, and SE, adjusted RR: 8.0; 95% CI: 2.1–30.2, p=0.002. Conclusion Patients with stable chest pain, stenosis by CTA and a normal FFRCT test result have a low risk of adverse outcomes during 3 years of follow-up. An abnormal FFRCT identifies patients at increased risk of death or spontaneous MI. These associations are consistent in patients with high levels of CAC. Funding Acknowledgement Type of funding sources: None.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention

Background and aimsHigh-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. MethodsWe examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. ResultsMean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74–0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66–0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72–1.46), CAC = 1–99 was 0.71 (95% CI, 0.51–0.99), and CAC≥100 was 0.67 (95% CI, 0.52–0.84). A similar association was seen in tertiles of DHA by CAC category. ConclusionsIn an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Abstract 466: Fhl5 Enhances Vascular Calcification By Regulating Smooth Muscle Cell Transcriptional Networks

Coronary artery calcium (CAC) is a hallmark of coronary artery disease (CAD) with increased CAC levels associated with increased risk for CAD related morbidity and mortality. The development of CAC is a pathological process driven by the modulation of smooth muscle cells (SMCs) and maladaptive extracellular matrix remodeling. In the most recent multi-ancestry meta-analysis of more than 35,000 individuals, FHL5 (Four-and-a-half LIM domains 5) was prioritized as a novel CAC gene through Bayesian colocalization and epigenomic analyses. scRNA-seq studies of human coronary and carotid arteries revealed high enrichment of FHL5 gene expression in SMC and pericyte populations. These preliminary studies motivate our hypothesis that FHL5 functions as a transcriptional regulator of vascular remodeling pathways associated with increased CAC risk. Following treatment of SMCs with a calcifying cocktail, stable FHL5 overexpression promoted the osteogenic SMC phenotypic transition, characterized by increased levels of osteogenic activators and reduced expression of SMC contractile markers. This osteogenic gene signature correlated with increased SMC calcification, consistent with the direction of effect of the CAC risk allele. To provide insights into the transcriptional program regulated by FHL5 that contributes to the vascular calcification phenotype, we mapped FHL5 binding sites in SMCs using the CUT&amp;RUN method. We identified 17,201 FHL5 binding sites that overlapped the active enhancer mark H3K27ac. FHL5 target genes were enriched in pathways linked to vascular remodeling, such as cell adhesion and extracellular matrix organization. Moreover, risk variants for pulse pressure, a metric of arterial stiffness that is highly correlated with CAC, was enriched in FHL5 binding sites. Lastly, integration with FHL5 trans-eQTL target genes in STARNET arterial tissues revealed a network of CAD-associated candidate genes regulated by FHL5 in vitro and in vivo that impact SMC proliferation, migration, and calcification. Taken together, we provide evidence that FHL5 regulates a network of genes linked to arterial stiffness, which may explain the underlying mechanism of its genetic association with CAC in individuals from the general population.

Osteoporosis in patients with coronary artery disease after coronary bypas surgery

Aim. To determine the most significant predictors of an unfavorable progress of osteoporosis (OP) in men with coronary artery disease after coronary artery bypass grafting (CABG) according to long-term (5 years) follow-up data.Methods. The prospective study included 393 patients (men) hospitalized for CABG. All patients underwent multispiral computed tomography of the coronary and carotid arteries to assess the calcium score (CS) and determine the equivalent density of calcium deposits (EDCD), coronary angiography, and dual-energy X-ray absorptiometry. After 5 years (average 59 months) of follow-up, the prognosis (status alive/dead) was assessed in 335 patients. Mortality during follow-up in patients after CABG was 10.7% (36 patients died). 257 patients underwent repeated osteodensitometry, quantitative assessment of coronary and carotid calcification, assessment of the “end points” of bone status (osteoporotic fractures, osteoporosis).Results. During the five-year follow-up an increase in the prevalence of OP was noted from 76.1% to 90.7%, while in 43.6% of cases, the progression of OP was recorded. Fractures occurred in 39 patients (15.2%), and in 34 (13.2%) osteoporosis developed for the first time. OP progression is associated with smoking (OR 5.3, 95% CI 3.1–9.4), 30% or more carotid artery stenosis (OR 5.6, 95% CI 2.9–10.7), baseline severe (more than 400) calcification of the coronary arteries (OR 2.7 at 95% CI 1.3–9.8), low density of (EDCD less than 0.19 g/mm3 ) coronary (OR 1.7 at 95% CI 1.1–8.2) and carotid (OR 2.4, 95% CI 1.4–10.3) calcium deposits. Linear regression analysis made it possible to establish that the reliable predictors of an unfavorable course of OP are coronary CS, EDCD of the carotid arteries, and the absence of statin therapy.Conclusion. OP progression in patients in the long-term period (5 years) after CABG was noted in 43.6%. The predictors of OP progression and the complications are a high level of coronary artery calcification, a low EDCD in the carotid arteries, and 30% or more stenosis of the carotid arteries. Patients receiving statins were associated with a lower risk of osteoporosis.

Metabolomic Analysis of Coronary Heart Disease in an African American Cohort From the Jackson Heart Study

African American individuals have disproportionate rates of coronary heart disease (CHD) but lower levels of coronary artery calcium (CAC), a marker of subclinical CHD, than non-Hispanic White individuals. African American individuals may have distinct metabolite profiles associated with incident CHD risk compared with non-Hispanic White individuals, and examination of these differences could highlight important processes that differ between them. To identify novel biomarkers of incident CHD and CAC among African American individuals and to replicate incident CHD findings in a multiethnic cohort. This analysis targeted plasma metabolomic profiling of 2346 participants in the Jackson Heart Study (JHS), a prospective population-based cohort study that included 5306 African American participants who were examined at baseline (2000-2004) and 2 follow-up visits. Replication of CHD-associated metabolites was sought among 1588 multiethnic participants from the Women's Health Initiative (WHI), a prospective population-based multiethnic cohort study of 161 808 postmenopausal women who were examined at baseline (1991-1995) and ongoing follow-up visits. Regression analyses were performed for each metabolite to examine the associations with incident CHD and CAC scores. Data were collected from the WHI between 1994 and 2009 and from the JHS between 2000 and 2015. All data were analyzed from November 2020 to August 2021. Plasma metabolites. Incident CHD was defined as definite or probable myocardial infarction or definite fatal CHD in both the JHS and WHI cohorts. In the JHS cohort, silent myocardial infarction between examinations (as determined by electrocardiography) and coronary revascularization were included in the incident CHD analysis. Coronary artery calcium was measured using a 16-channel computed tomographic system and reported as an Agatston score. Among 2346 African American individuals in the JHS cohort, the mean (SD) age was 56 (13) years, and 1468 individuals (62.6%) were female. Among 1588 postmenopausal women in the WHI cohort, the mean (SD) age was 67 (7) years; 217 individuals (13.7%) self-identified as African American, 1219 (76.8%) as non-Hispanic White, and 152 (9.6%) as other races or ethnicities. In the fully adjusted model including 1876 individuals, 46 of 303 targeted metabolites were associated with incident CHD (false discovery rate q <0.100). Data for 32 of the 46 metabolites were available in the WHI cohort, and 13 incident CHD-associated metabolites from the JHS cohort were replicated in the WHI cohort. A total of 1439 participants from the JHS cohort with available CAC scores received metabolomic profiling. Nine metabolites were associated with CAC scores. Minimal overlap was found between the results from the incident CHD and CAC analyses, with only 3 metabolites shared between the 2 analyses. This cohort study identified metabolites that were associated with incident CHD among African American individuals, including 13 incident CHD-associated metabolites that were replicated in a multiethnic population and 9 novel metabolites that included N-acylamides, leucine, and lipid species. These findings may help to elucidate common and distinct metabolic processes that may be associated with CHD among individuals with different self-identified race.

Does coronary calcium score add value to European SCORE in an asymptomatic population?

Abstract Background Despite being a controversial subject, multiple guidelines mention the use of Coronary Artery Calcification (CAC) scoring in the cardiovascular risk prediction in the asymptomatic population. Adding CAC score to European SCORE (Systematic Coronary Risk Evaluation) may improve the prediction of MACE (Major Adverse Cardiovascular Events), providing better cardiovascular risk stratification. Purpose Our study aims to evaluate the impact of CAC severity in MACE prediction compared with SCORE and estimate the additional value of CAC score in cardiovascular risk stratification in a low- risk region and asymptomatic population. Methods and results The study consisted of a prospective registry of 1110 asymptomatic individuals free of known coronary heart disease, enrolled from the GENEMACOR study and referred for computed tomography for the CAC scoring assessment. The mean age was 51.6±8.2 years, and 74.1% were male. This population was followed for a mean of 5.2±3.3 years for the primary endpoint of all-cause of cardiovascular events. The extent of CAC differs significantly between men and women in the same age group. Therefore, the distribution of CAC score by age and gender was done using Hoff's nomogram (a). According to this nomogram, 3 categories were created: low CAC (0≤CAC&amp;lt;100 and P&amp;lt;50); moderate CAC (100≤CAC&amp;lt;400 or P50–75) and high CAC (CAC≥400 or P&amp;gt;75). Through a Cox regression for MACE occurrence, SCORE does not remain in the equation, and the higher severity level of CAC presented a significant risk of MACE occurrence with an HR of 7.943 (95% CI 2.948 – 21.401; p&amp;lt;0.0001). Using the C-index, CAC was superior to SCORE (0.729 vs 0.615; p&amp;lt;0.0001). Adding CAC score to SCORE increased MACE prediction compared to SCORE alone (AUC 0.77 vs 0.615; p=0.003). Conclusion Our results point to the importance of the CAC score inclusion in primary prevention to improve cardiovascular risk stratification. CAC score in clinical practice could have a prognostic impact on MACE prediction. Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings. Funding Acknowledgement Type of funding sources: None. Table 1

The Effect of Sodium Thiosulfate on Coronary Artery Calcification in Hemodialysis Patients.

This study aimed to effectively control the disease process of hemodialysis outpatients. Hemodialysis secondary hyperparathyroidism patients were randomly divided into the control group and treatment group. The control group was treated with routine treatment, and the treatment group was treated with sodium thiosulfate based on the control group. The changes of serum calcium, phosphorus, whole parathyroid hormone, calcium-phosphorus product and coronary artery calcification (CAC) score, as well as the relief of clinical symptoms, postoperative complications and recurrence in the preoperative and postoperative periods were observed. The levels of C-reactive protein and CAC scores were significantly decreased in the treatment group after treatment. While there was no significant difference in blood calcium, blood phosphorus, PTH, calcium-phosphorus product, and CAC score in the control group after treatment. And after treatment, the proportion of skin pruritus, myasthenia, bone pain, insomnia, restless legs syndrome, and other symptoms in the treatment group was significantly decreased compared with those before treatment, but there was no significant change in the control group before and after treatment. Sodium thiosulfate can reduce the high level of CAC in hemodialysis patients obviously.