Extracoronary Calcification Research Articles

The Predictive Value of Aortic Calcification on Computed Tomography for Major Cardiovascular Events.

As the prevalence of cardiovascular disease continues to increase, early identification of patients at high risk of major adverse cardiovascular events (MACE) using reliable diagnostic modalities is important. Transcatheter aortic valve implantation (TAVI) is a minimally invasive percutaneous procedure used to replace the aortic valve with a bioprosthetic one, often without the need for surgery. Extra coronary calcification in the ascending and/or descending thoracic aorta, aortic arch, and abdominal aorta has recently been identified as a method to quantify the extent of atherosclerotic cardiovascular disease. However, its definitive role in the prediction of MACE remains unclear. We performed a comprehensive review to summarize the current literature on the diagnostic and predictive value of thoracic and abdominal aortic calcification, as quantified in computed tomography, for the association, risk stratification, and prediction of MACE and after TAVI procedures. Despite increasing evidence, the predictive role of thoracic calcification still remains unproven, with a need for carefully tailored studies to confirm these findings.

Coronary and Extra-coronary Subclinical Atherosclerosis to Guide Lipid-Lowering Therapy.

To discuss and review the technical considerations, fundamentals, and guideline-based indications for coronary artery calcium scoring, and the use of other non-invasive imaging modalities, such as extra-coronary calcification in cardiovascular risk prediction. The most robust evidence for the use of CAC scoring is in select individuals, 40-75 years of age, at borderline to intermediate 10-year ASCVD risk. Recent US recommendations support the use of CAC scoring in varying clinical scenarios. First, in adults with very high CAC scores (CAC ≥ 1000), the use of high-intensity statin therapy and, if necessary, guideline-based add-on LDL-C lowering therapies (ezetimibe, PCSK9-inhibitors) to achieve a ≥ 50% reduction in LDL-C and optimally an LDL-C < 70 mg/dL is recommended. In patients with a CAC score ≥ 100 at low risk of bleeding, the benefits of aspirin use may outweigh the risk of bleeding. Other applications of CAC scoring include risk estimation on non-contrast CT scans of the chest, risk prediction in younger patients (< 40 years of age), its value as a gatekeeper for the decision to perform nuclear stress testing, and to aid in risk stratification in patients presenting with low-risk chest pain. There is a correlation between extra-coronary calcification (e.g., breast arterial calcification, aortic calcification, and aortic valve calcification) and incident ASCVD events. However, its role in informing lipid management remains unclear. Identification of coronary calcium in selected patients is the single best non-invasive imaging modality to identify future ASCVD risk and inform lipid-lowering therapy decision-making.

Abstract 11959: The Relationship of Matrix Gla Protein With Coronary and Extracoronary Calcification in the Multi-Ethnic Study of Atherosclerosis

Introduction: Vascular calcification regulators are understudied. Matrix Gla protein (MGP) is a calcification inhibitor, and its inactive dephosphorylated-uncarboxylated (dp-ucMGP) form has been linked to calcification. The longitudinal relationship of dp-ucMGP with coronary and extracoronary artery calcification in large populations is unknown. Hypothesis: Higher levels of dp-ucMGP may be associated with greater coronary artery, ascending thoracic aortic, and descending thoracic aortic calcification (CAC, ATAC, DTAC). Aim: To determine the association of dp-ucMGP with CAC, ATAC, and DTAC. Methods: Calcification was measured on serial thoracic computed tomography (CT) scans in the Multi-Ethnic Study of Atherosclerosis (MESA, n=6814). Dp-ucMGP was measured at baseline in a random subset of available serum samples (n=2663), 2539 included in the fully adjusted models) in participants with a baseline (2000-02) and follow-up CTs at Exam 5 (2010-12) ( InaKtif MGP ELISA, Perkin Elmer, Waltham, MA). Linear mixed effect models were used to determine the association of baseline dp-uc MGP levels with long-term CAC, ATAC, and DTAC incidence and progression. Results: Participants were on average 61 + 9 years, 51.3% women, and 37.7% white. For each one standard deviation (178 pmol/L) increase in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p&lt;0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p=0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p&lt;0.001) AU/year, in fully adjusted models. Conclusion: We found an association of the inactive form of matrix Gla protein, dp-ucMGP, with long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate MGP as a calcification regulator and possible therapeutic target.

Abstract P438: Physical Activity and Calcification of Coronary Arteries, Aorta, and Cardiac Valves: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Regular physical activity (PA) has been associated with reduced risk of coronary heart disease, but conflicting results have been reported regarding its association with coronary artery calcification (CAC), one of the strongest predictors of cardiovascular disease. Moreover, different domains of PA (e.g., sports vs. work) and extra coronary calcification (ECC) have not been extensively studied in this context. Methods: We investigated 2,025 ARIC participants (age 73-95 years) who had no coronary heart disease and underwent a non-contrast cardiac-gated computed tomography scan at visit 7 (2018-19). PA was based on a modified Baecke questionnaire, which provides total and domain-specific (sport, non-sport leisure, and work) PA scores. We modeled the cumulative PA scores in middle-age at visit 1 (1987-89) and visit 3 (1993-95). We explored continuous CAC and ECC (log-transformed [Agatston score+1]) or any CAC and ECC (Agatston score &gt;0 vs. 0) as dependent variables using linear regression and multivariable logistic models, as appropriate. Results: Higher total and domain-specific PA scores showed no association with lower CAC. Among ECC, descending aorta calcification demonstrated the strongest association with total PA scores (coefficient -0.10 [95% CI -0.21, 0.01], p=0.075) ( Figure ). When specific domains were explored, higher sport and work PA scores were significantly associated with lower descending aorta calcification. When we analyzed any CAC and ECC as the outcome variable, the results were generally consistent. Conclusions: Higher PA in midlife was associated with lower calcification of descending aorta in late life. Our results further support the health benefits of PA and unique pathological process across different vascular beds.

Abstract P210: Dietary Calcium and Phosphorus Intakes at Middle Age and Their Associations With Vascular Calcification at Older Age: The Atherosclerosis Risk in Communities (ARIC) Study

Background: High dietary calcium and phosphorus intakes may accelerate vascular calcification. A few studies have explored the association of dietary calcium and phosphorus intakes with vascular calcification but reported inconsistent results. Most studies relied on dietary assessment at one time point and evaluated only coronary artery calcification. Aim: To assess the associations of dietary calcium and phosphorus intakes over two time points during middle age with coronary artery and extra-coronary calcification at older age. Methods: We studied 1,940 ARIC participants who underwent chest CT scans at ≥75 years of age in 2018-19 and completed a 66-item food frequency questionnaire at two earlier visits (1987-89 and 1993-95). We calculated the average of dietary calcium and phosphorus intakes across these two visits. Calcification was quantified as Agatston score in coronary arteries, ascending aorta, descending aorta, aortic valve ring, aortic valve, and mitral valve. We ran multivariable linear (for continuous Agatston score) and logistic regression models (for Agatston score &gt;75 th percentile). Results: The mean dietary calcium and phosphorus intake was 659 mg/day and 1,074 mg/day, respectively. Overall, we did not observe any positive associations of dietary calcium intake with vascular/valvular calcification. Rather, we saw its inverse association with ascending aorta calcification (Figure). In contrast, dietary phosphorus was not associated with the calcification of any vascular beds. The results were largely similar in linear regression models and after excluding 332 participants (17%) taking calcium supplements. Conclusion: Dietary calcium intake at middle age was largely neutral in its association with vascular calcification while showing a mild inverse association with ascending aorta calcification at older age. No evident associations were seen for dietary phosphorus. Our findings do not support a concern that a calcium or phosphorus-rich diet may accelerate vascular calcification.

Kidney function, bone-mineral metabolism markers, and calcification of coronary arteries, aorta, and cardiac valves in older adults

Background and aimsThe contribution of kidney dysfunction, especially at mild-to-moderate stages, and bone-mineral metabolism (BMM) markers to vascular calcification remains controversial or unclear. We comprehensively evaluated the association of kidney and BMM markers with coronary artery calcification (CAC) and extra-coronary calcification (ECC). MethodsIn 1931 ARIC participants (age 73–95 years) without coronary heart disease at visit 7 (2018–19), we investigated the associations of estimated glomerular filtration rate (eGFR) (with creatinine, cystatin C, and both) and five serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) with high CAC and ECC (sex-race specific ≥75th vs. <75th percentile Agatston score) or any vs. zero CAC and ECC using multivariable logistic regression. For eGFR and BMM markers, we took their weighted cumulative averages from visit 1 (1987–89) to visit 5 (2011–13). ResultsLower eGFR, regardless of equations used, was not robustly associated with high CAC or ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed robust associations with high CAC (only when modeled continuously) and ECC, independently of kidney function (e.g., odds ratio 1.94 [95%CI 1.38–2.73] for high aortic valve calcification, in the highest vs. lowest quartile). Results were generally consistent when analyzing any CAC or ECC, although cystatin C-based eGFR <60 mL/min/1.73 m2 became significantly associated with mitral valve calcification (odds ratio 1.69 [1.10–2.60]). ConclusionsAmong kidney and BMM measures tested, only serum phosphorus demonstrated robust associations with both CAC and ECC, supporting a key role of phosphorus in the pathophysiology of vascular calcification.

Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?

The coronary artery calcium score is a guideline-endorsed aid for further risk stratification in the primary prevention of atherosclerotic cardiovascular disease. The non-contrast scan performed for detection of coronary artery calcium also gives an opportunity to visualize calcifications in the thoracic aorta and in the heart valves, at no additional cost or radiation exposure. The purpose of this review was to discuss the potential clinical value of measuring thoracic aortic calcification, aortic valve calcification, and mitral annulus calcification. After two decades of active research, all three calcifications have been extensively evaluated, across various cohorts. We discuss classic and recent studies, current knowledge gaps, and future directions in this space. The added value of these measurements has traditionally been considered modest at best, and they are not currently discussed in relevant primary prevention guidelines in North America and Europe. However, recent studies evaluating high thoracic calcification thresholds and younger populations have further enriched this space. Specifically, some studies suggest that detection of severe thoracic aortic calcification may be helpful in further risk assessment and that detection of aortic valve calcifications may have important prognostic implications in younger individuals. Although more research is needed, particularly in larger young-to-middle-aged cohorts, future guidelines might consider including these features as risk-enhancing factors.

Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

BackgroundLipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age.Methods and ResultsLp(a) was measured at ARIC visit 4 (1996–1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018–2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34–2.47), CAC (aOR, 1.40; 95% CI, 1.08–1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07–1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06–1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05–1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex.ConclusionsElevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Coronary Artery Calcium Scoring: Current Status and Future Directions.

Coronary artery calcium (CAC) scores obtained from CT scans have been shown to be prognostic in assessment of the risk for development of cardiovascular diseases, facilitating the prediction of outcome in asymptomatic individuals. Currently, several methods to calculate the CAC score exist, and each has its own set of advantages and disadvantages. Agatston CAC scoring is the most extensively used method. CAC scoring is currently recommended for use in asymptomatic individuals to predict the risk of developing cardiovascular diseases and the disease-specific mortality. In specific subsets of patients, the CAC score has also been recommended for reclassifying cardiovascular risk and aiding in decision making when planning primary prevention interventions such as statin therapy. The progression of CAC scores on follow-up images has been shown to be linked to risk of myocardial infarction and cardiovascular mortality. While the CAC score is a validated tool used clinically, several challenges, including various pitfalls associated with the acquisition, calculation, and interpretation of the score, prevent more widespread adoption of this metric. Recent research has been focused extensively on strategies to improve existing scoring methods, including measuring calcium attenuation, detecting microcalcifications, and focusing on extracoronary calcifications, and on strategies to improve image acquisition. A better understanding of CAC scoring approaches will help radiologists and other physicians better use and interpret these scores in their workflows. An invited commentary by S. Gupta is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis

BackgroundHepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary...

Favorable Cardiovascular Health Is Associated With Lower Prevalence, Incidence, Extent, and Progression of Extracoronary Calcification: MESA.

Ideal cardiovascular health (CVH) is associated with a lower incidence of cardiovascular disease. Extracoronary calcification (ECC)-measured at the aortic valve, mitral annulus, ascending thoracic aorta, and descending thoracic aorta-is an indicator of systemic atherosclerosis. This study examined whether favorable CVH was associated with a lower risk of ECC. We analyzed data from MESA (Multi-Ethnic Study of Atherosclerosis) participants aged 45 to 84 years without cardiovascular disease at baseline. ECC was measured by noncontrast cardiac computed tomography scan at baseline and after an average of 2.4 years. Prevalent ECC was defined as an Agatston score >0 at the baseline scan. Incident ECC was defined as Agatston score >0 at the follow-up scan among participants with Agatston score of 0 at the baseline scan. Each CVH metric (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose) was scored 0 to 2 points, with 2 indicating ideal; 1, intermediate; and 0, poor. The aggregated CVH score was 0 to 14 points (0-8, inadequate; 9-10, average; 11-14, optimal). We used Poisson and linear mixed-effects regression models to examine the association between CVH and ECC adjusted for sociodemographic factors. Of 6504 participants, 53% were women with a mean age (SD) of 62 (10) years. Optimal and average CVH scores were associated with lower ECC prevalence, incidence, and extent. For example, optimal CVH scores were associated with 57%, 56%, 70%, and 54% lower risk of incident aortic valve calcification, mitral annulus calcification, ascending thoracic aorta calcification, and descending thoracic aorta calcification, respectively. In addition, optimal and average CVH scores were associated with lower ECC progression at 2 years, although these associations were only significant for mitral annulus calcification and descending thoracic aorta calcification. In this multiethnic cohort, favorable CVH was associated with a lower risk of extracoronary atherosclerosis. These findings emphasize the importance of primordial prevention as an intervention to reduce the burden of cardiovascular disease.

Abstract MP61: 1-year Prognosis By Coronary Artery And Extra-coronary Calcification In The 75-and-older Population

Background: Coronary artery calcium (CAC) is one of the most potent predictors of cardiovascular disease (CVD). Also, thoracic extra-coronary calcification (ECC) (e.g., aortic valve calcification) has provided additional prognostic information beyond CAC. However, data on CAC and ECC as predictors of CVD outcomes are limited in individuals aged ≥75 years and rarely report near-term prognosis despite its importance in the 75-and-older population given life expectancy. Methods: In 1,672 ARIC participants (age 75-94 years) without history of clinical coronary heart disease (CHD) at visit 7 (2018-2019), we assessed the associations of CAC and ECC with CVD (including CHD, stroke, and heart failure) over a median follow-up of 1.1 (IQI 0.7-1.5) years (46 CVD total cases), using adjusted Cox models. CAC and ECC were modeled categorically (Agatston scores 0-99 [reference], 100-299, and 300+) and continuously (log[Agatston score+1]). Results: Higher scores of CAC and calcium in the aortic valve (only when modeled continuously) and ascending aorta were significantly associated with elevated risk of CVD (e.g., adjusted hazard ratio [HR]: 2.79 [95% CI 1.21, 6.44] for CAC 300+ and 5.90 [2.42, 14.39] for ascending aorta calcium 300+ vs. 0-99.) ( Table ). We confirmed consistent results after excluding participants with prevalent stroke, and the association of aortic valve calcium 300+ with CVD became statistically significant (HR 2.31 [95% CI 1.02, 5.24]. When each CVD outcome was analyzed separately, significant associations with CHD and heart failure were shown in CAC (only when modeled continuously) and ascending aorta calcium (e.g., 4.98 [95% CI 1.10, 22.58] for CHD and 6.88 [2.14, 22.04] in ascending aorta calcium 300+). Conclusions: Coronary artery, ascending aorta, and aortic valve calcifications were positively associated with 1-year risk of CVD in 75+ year old. Our results support the prognostic value of CAC and ECC even in very old adults and suggest distinct prognostic implications of different vascular beds.

Abstract 10670: Kidney Function, Bone-Mineral Metabolism Markers, and Calcification of Coronary Arteries, Aorta, and Cardiac Valves in Older Adults

Background: Kidney function is a crucial determinant of bone-mineral metabolism (BMM); however, the contribution of kidney dysfunction, especially at mild to moderate stages, to vascular calcification remains controversial. Moreover, little is known about whether BMM markers are associated with coronary artery calcification (CAC) and extra-coronary calcification (ECC) beyond kidney function. Methods: In 1935 ARIC participants (age 73-95 years) with no coronary heart disease and data on CAC and ECC at visit 7 (2018-2019), we evaluated estimated glomerular filtration (eGFR) (based on creatinine, cystatin C, and both) and serum BMM markers (calcium, fibroblast growth factor 23, magnesium, parathyroid hormone, and phosphorus) as exposures. The exposures were modeled as weighted averages over ~15 years (visit 1 [1987-89] to visit 5 [2011-13] to allow a lag time for vascular calcification), and the outcome variables were high CAC and ECC (sex-race specific ≥75 th vs. &lt;75 th percentile Agatston score) or any CAC and ECC (Agatston score &gt;0 vs. 0) using multivariable logistic regression. Results: Low eGFR (overall range 30-149 mL/min/1.73m 2 ), regardless of equations, was not robustly associated with high CAC and ECC. Among BMM markers, only higher phosphorus levels, even within the normal range, showed significant associations with high CAC and ECC, independent of kidney function ( Figure ). Considering presence of any calcification, results were generally consistent, although cystatin C-based eGFR &lt;60 mL/min/1.73m 2 was associated with mitral valve calcification (present in 47%) (odds ratio 1.70 [95% CI 1.13, 2.58]). Conclusion: Cumulative exposure to lower eGFR showed weak associations with vascular calcification in community-dwelling older adults. Among BMM markers, phosphorus was most robustly associated with CAC and ECC beyond kidney function. Our results suggest a potential key role of phosphorus in the pathophysiology of vascular calcification.

Abstract 11104: Association of Cigarette Smoking and Coronary Artery and Extra-Coronary Calcification in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Smoking is a major risk factor for atherosclerosis, but its impact is heterogeneous across different vascular beds (e.g., stronger association with peripheral artery disease than coronary disease). However, whether the association of cigarette smoking with vascular calcification is (dis)similar across vascular beds is uncertain. Methods: In 1,961 ARIC participants without a history of coronary heart disease at visit 7 (2018-19), we quantified the associations of pack-years of smoking and years since cessation with coronary artery calcium (CAC) and extra-coronary calcification (ECC) using multivariable logistic regression models. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) were defined as Agatston score &gt;75th percentile and were analyzed separately as dependent variables. Results: Pack-years of smoking demonstrated an independent and robust dose-response relationship with CAC, ascending and descending aorta calcification, and aortic valve ring calcification (Table). The association was particularly evident for descending aorta calcification (e.g., adjusted odds ratio [aOR] 3.57 [95%CI 2.46-5.19] for ≥40 pack-years). The results were similar for the duration since smoking cessation, with the most prolonged risk seen for the descending aorta (i.e., even ≥30 years of smoking cessation had OR of 1.34 [1.03-1.47]). Aortic valve and mitral valve calcification demonstrated modest associations with smoking. Conclusions: Cigarette smoking showed a robust association with coronary and extra-coronary calcification, and its association was particularly strong with descending aorta calcification. Our findings further emphasize the harm of smoking on broad ranges of vascular beds and simultaneously highlight unique pathophysiologic mechanisms across different vascular beds and cardiac valves.

Abstract 11401: The Association of Carotid-Femoral Pulse Wave Velocity with Coronary and Extra-Coronary Calcification: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Increased carotid-femoral pulse wave velocity (cfPWV) is considered the standard non-invasive measurement of central arterial stiffness and is associated positively with cardiovascular disease. However, its relationship with coronary artery calcium (CAC) and extra-coronary calcification (ECC) in older adults is unclear. Hypothesis: cfPWV has a stronger relationship with aortic calcification as it is a large conduit artery, compared to small end-organ coronary arteries. Methods: In 1,409 ARIC participants aged 74-91 without prior coronary heart disease at visit 7 (2018-19), we quantified associations of cfPWV and high CAC or ECC using multivariable logistic regression models. PWV test was conducted at either visit 6 (2016-2017) or 7, and 725 participants completed PWV test at visit 6. cfPWV was measured using VP-1000plus (Omron Healthcare) and was categorized into tertiles. High CAC and ECC (aortic valve, aortic valve ring, mitral valve, ascending aorta, and descending aorta calcification) &gt;75th percentile of Agatston score were analyzed separately as dependent variables. Results: Those in the highest (vs. lowest) tertile of cfPWV were significantly more likely to have high CAC (adjusted OR 1.66 [1.19, 2.33]) (Table). The strongest association was seen for high descending aorta calcification, with adjusted ORs of 3.53 (2.47, 5.03) for the highest tertile of cfPWV and 1.90 (1.33, 2.71) for the middle tertile, compared with the lowest tertile. High mitral valve calcification but not aortic valve calcification was significantly associated with cfPWV. Conclusions: Higher cfPWV was robustly associated with high calcification of some, but not all, vascular beds examined, especially descending aorta calcification. Our findings further support unique pathophysiological processes across different vascular beds. The robust association between cfPWV and mitral valve calcification warrants future investigation.

Associations of endogenous sex hormone levels with the prevalence and progression of valvular and thoracic aortic calcification in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsSex hormones (SH) may contribute to sex differences in cardiovascular disease (CVD). High free testosterone (T) and low sex hormone binding globulin (SHBG) have been associated with progression of coronary artery calcification in women. We now examined the association of SH with extra-coronary calcification (ECC) prevalence and progression among MESA participants. MethodsWe studied 2,737 postmenopausal women and 3,130 men free of clinical CVD with baseline SH levels. ECC measurements [ascending and descending thoracic aortic calcification (ATAC, DTAC), mitral annular calcification (MAC), aortic valve calcification (AVC)] were obtained by computed tomography at baseline and after 2.4 ± 0.9 years. We used multivariable Poisson regression to evaluate associations with ECC prevalence and incidence (Agatston scores >0) and linear mixed effects models for ECC progression, per 1-SD increment in log(SH) in women and men separately. ResultsThe mean age was 65 ± 9 and 62 ± 10 years for women and men, respectively. In women, greater free T and lower SHBG were associated with MAC incidence in a demographic-adjusted model only. In men, lower free T was associated with MAC prevalence, DTAC incidence and progression, while greater SHBG was associated with MAC prevalence and DTAC progression after further adjusting for CVD risk factors. ConclusionsIn this diverse cohort free of CVD, we found some associations of SH with ECC measures. In particular, free T was inversely associated with prevalent MAC and DTAC progression in men independent of CVD risk factors. SH may influence vascular calcification, but further work is needed to understand clinical implications of these findings.

Cardiac calcium score in systemic sclerosis.

Cardiac coronary Ca score (CCS), and extra coronary Ca score (ECCS) estimation in asymptomatic systemic sclerosis (SSc) patients and their relation to different disease and patients' variables. The CCS and ECCS were estimated in asymptomatic 20 SSc patients compared to 20 age and sex-matched healthy control using non-contrast cardiac computed tomography. All were applied for cardiac history taking, examination, echocardiography, body mass index (BMI), complete blood picture, erythrocyte sedimentation rate, and lipid profile estimation. The SSc patients were 11 females and 9 males with a mean age of (42.55 ± 9.145) and mean disease duration (12.9 ± 6.774). CCS was reported in 9 (45%) SSc cases and 2 (10%) of the control; (p = 0.013) and was significantly greater in SSc patients (58.4 ± 175.443) than in the control group (0.7 ± 2.25); (p = 0.01). The ECCS was significantly higher in SSc cases (194.45 ± 586.511) than control group (2.8 ± 7.8); (p = 0.001) and reported in 16 (80%) SSc cases and 3 (15%) of controls; (p = 0.000). Limited scleroderma cases had higher scores than diffuse type. Patients with total ca score (> 100) were older (p = 0.016), had longer disease duration (p = 0.001) and greater BMI (p = 0.002). Significant correlation was found between the log-transformed CCS and disease duration, age, BMI, left ventricular mass, and mass index. Systemic sclerosis patients are at increased risk of subclinical cardiovascular disease determined by cardiac Ca scoring as a noninvasive and reliable method. Extra coronary calcification may be an earlier indicator for this. Disease duration is a determinant risk factor for cardiac calcification in SSc. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • Systemic sclerosis patients are at high risk of accelerated atherosclerosis and cardiovascular diseases. Coronary atherosclerosis was previously estimated in SSc patients through coronary angiography. A novel method of assessing coronary artery disease is the coronary calcium score, as determined by multidetector computed tomography, it measures coronary artery calcification that occurs in atherosclerotic plaque. In this study, the cardiac coronary and extra coronary Ca score were evaluated in relation to disease characteristics in asymptomatic SSC patients for early detection of coronary artery disease.

Abstract P214: Ideal Cardiovascular Health And Progression Of Extra-coronary Calcification In The Multi-ethnic Study Of Atherosclerosis

Background: Ideal cardiovascular health (CVH) is associated with a lower incidence of cardiovascular disease (CVD). Extra-coronary calcification (ECC) – measured at the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta (ATAC) and descending thoracic aortic (DTAC) – is an indicator of systemic atherosclerosis. However, the association between ideal CVH and ECC is unknown. This study examined whether favorable CVH was associated with a lower risk of ECC. Methods: We analyzed data from 6,504 men and women aged 45-84 years from MESA, a multi-ethnic cohort free of CVD at baseline. Extra-coronary calcification [AVC, MAC, ATAC and DTAC] was measured by non-contrast cardiac CT scan at baseline and after an average of 2.4 years. Prevalent and incident ECC were defined as an Agatston score &gt;0. Each CVH metric (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) was scored 0-2 points, with 2 indicating “ideal”, 1 “intermediate” and 0 “poor”. The maximum CVH score attainable ranged from 0-14 points (inadequate score: 0-8; average: 9-10; optimal: 11-14). We used Poisson regression and linear mixed-effect models to examine the association between CVH and ECC adjusted for age, sex, race/ethnicity, education, income, health insurance and study site. Results: The mean (SD) age of participants was 62 (10) years, 53% were women, 39% White, 12% Chinese American, 26% Black and 22% Hispanic. Optimal and average CVH scores were associated with a lower prevalence and incidence of ECC as well as lower ECC extent at baseline compared to inadequate scores (Table). In addition, optimal and average CVH scores were associated with less ECC progression at 2 years although the associations were only significant for MAC and DTAC. Conclusion: In this multi-ethnic cohort, favorable CVH was associated with a lower risk of developing extra-coronary atherosclerosis. These findings underscore the importance of primordial prevention as an intervention to reduce the burden of CVD.

Abstract P217: Associations Of Adipokine Levels With The Prevalence And Extent Of Valvular And Thoracic Aortic Calcification: The Multi-ethnic Study Of Atherosclerosis

Introduction: Extra-coronary calcification (ECC), a marker of systemic atherosclerosis, is an independent risk factor for incident cardiovascular disease (CVD). Adipokines participate in many cardiometabolic pathways and may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well established. We hypothesized that higher leptin and resistin levels and lower adiponectin levels would be associated with a greater extent of ECC. Methods: We performed a cross-sectional analysis of 1,955 community dwelling adults free of clinical CVD in the MESA cohort. Serum adipokine levels and a cardiac CT scan were obtained at exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin (per 1 SD of log transformed adipokine) with the prevalence and extent of ECC. Results: The mean age of participants was 62±10 years; 50% were women, 40% white, 13% Chinese, 21% Black and 26% Hispanic. In a model adjusted for demographics, we found 1) adiponectin was inversely associated with AVC prevalence and extent; 2) leptin was positively associated with MAC prevalence and extent; and 3) resistin was positively associated with ATAC prevalence and extent and with DTAC prevalence. After full adjustment for BMI and other CVD risk factors ( Table ), adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC or DTAC after full adjustment. Conclusion: In this diverse cohort free from clinical CVD, we found significant associations between selected adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.

Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.

There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63-6.11), 7.57- (5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25-2.16), 1.66- (1.22-2.25), 1.51- (1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.