Progression Of Coronary Artery Calcification Research Articles

Physical Activity and Progression of Coronary Artery Calcification in Men and Women

ImportancePrior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time.ObjectiveTo explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time.Design, Setting, and ParticipantsThis cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024.ExposuresPA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk.Main Outcomes and MeasuresNegative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU).ResultsAmong 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, −0.1% to 0.1%; women: 95% CI, −0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women.Conclusions and RelevanceThis study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.

Longitudinal albuminuria patterns predict coronary artery calcification progression: Findings from the Coronary Artery Risk Development in Young Adults study

Background and aimsAlbuminuria is an established risk factor for adverse cardiovascular outcomes. However, few studies have characterized longitudinal albuminuria patterns based on long-term measurement of urine albumin-to-creatinine ratio (UACR) levels. We aimed to evaluate the association between longitudinal albuminuria patterns in midlife adults and subsequent CAC progression. MethodsWe included 1919 participants with CAC assessment by computed tomography from CARDIA (Coronary Artery Risk Development in Young Adults) study. CAC progression was determined for each individual as the difference of logarithmic CAC scores at follow-up and baseline. Albuminuria patterns across a 10-year span were estimated by longitudinal UACR levels. Multivariable general linear models were used to evaluate the association of long-term albuminuria patterns with CAC progression. ResultsOf the 1919 included participants, 583 (30.4 %) participants experienced CAC progression, and the mean (SD) age was 50.4 (3.5) years at year 25. A total of four dynamic albuminuria patterns were identified. After multivariable adjustment, there were significant differences in CAC progression by albuminuria patterns as demonstrated as percent change in CAC with 36.0 % (SE, 1.5) progression for mid- and late-life normoalbuminuria group, 46.0 % (SE, 7.6) for midlife normoalbuminuria and late-life high albuminuria group, 52.4 % (SE, 7.1) for midlife high albuminuria and late-life normoalbuminuria group, and 54.5 % (SE, 8.7) for mid- and late-life high albuminuria group (p = 0.019). Similar findings were also observed in CAC volume score changes. ConclusionsLongitudinal albuminuria patterns across a 10-year span were associated with worse CAC progression independent of baseline CAC level and albuminuria changes, suggesting that it may provide early identification of high-risk individuals with dynamic rises in albuminuria who may benefit from aggressive risk factor modification.

RELATIONSHIP BETWEEN MITRAL ANNULAR CALCIFICATION AND CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC INDIVIDUALS

Objective: Despite the common atherosclerotic origins of mitral annular calcification (MAC) and coronary artery calcification (CAC), the relationship between MAC and CAC is not fully understood. We aimed to identify the factors associated with prevalent MAC and CAC, and also with their progression. Design and method: Using data from the KOrea Initiatives on Coronary Artery (KOICA) registry, 722 asymptomatic individuals who underwent health screening with serial cardiac computed tomography (CT) were selected for analysis. MAC and CAC were identified on CT, and the severity quantified using Agatston units (AU). The associations between the prevalence, severity, and the annualized progression rate of MAC and CAC were identified using multivariable regression models. Results: On initial CT, 47 (6.5%) participants had prevalent MAC and 334 (46.3%) had prevalent CAC. Increasing CAC severity was associated with a significantly higher probability of prevalent MAC (OR per 100 AU increase 1.06, 95% CI 1.05-1.07, p<0.001) even after correction for baseline characteristics. Similar results were true when CAC severity was assessed as a graded variable. Other factors associated with MAC were older age, female sex, higher body-mass index, diabetes, higher systolic blood pressure, and left atrial volume index. In those with prevalent MAC and CAC, the factors associated with a higher MAC progression rate were initial MAC severity (p<0.001), female sex (p=0.01), and higher serum phosphorus (p<0.001), while the factors associated with a higher CAC progression rate were initial CAC severity (p<0.001) and higher low-density lipoprotein cholesterol (p=0.02). Conclusions: We observed a close correlation between MAC and CAC, which is in accord with their common atherosclerotic origin. However, the differences in risk factors associated with the progression rate of MAC and CAC suggest the importance of site-specific mechanisms in the progression of calcification.

Association between progression of coronary artery calcification and development of kidney failure with replacement therapy: Findings from KNOW-CKD study

Background and aimsHigh coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). MethodsWe analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1–199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. ResultsDuring a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02–2.87) and 2.55 (95 % CI, 1.07–6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. ConclusionsCAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression.

GlycA Levels Independently Predict Coronary Artery Calcium Incidence and Progression in the ELSA-Brasil Cohort (Brazilian Longitudinal Study of Adult Health)

Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Elevated GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy individuals. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and two interval CAC assessments between 2010 through 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC > 0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were female, 54.6% and 16.1% (429/2690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 μmol/L, and the incidence of CAC was 13.1% (280/2,129). GlycA level odds ratio (OR) for CAC incidence was 1.002 [95% confidence interval (CI) 1.0005-1.005, p=0.016] adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and comorbidities. The GlycA (≤p25 vs ≥p75) OR for CAC progression (Berry definition) was 1.77 (95% CI 1.07-2.96, p=0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.

Steatotic liver disease and its newly proposed sub-classifications correlate with progression of the coronary artery calcium score.

A new nomenclature, Steatotic Liver Disease (SLD), has been proposed by consensus with sub-classifications and requires evidence-based validation. We assessed whether the presence and severity of SLD, as well as its sub-classifications, are associated with the progression of coronary atherosclerosis. This longitudinal cohort study included 13,811 adults who participated in repeated regular health screening examinations between January 1, 2004 and December 31, 2021 that included assessments of their coronary artery calcium (CAC) scores. SLD was defined using abdominal ultrasonography and classified as metabolic dysfunction associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and cryptogenic SLD. SLD severity was assessed using fibrosis-4 (FIB-4) scores. The progression of CAC scores was measured using multidetector CT scans. The average duration of follow-up was 5.8 years. During follow-up, the annual rate of CAC progression in participants with and without SLD was 18% (95% CI 17%-19%) and 14% (95% CI 13%-14%) (p < 0.01), respectively. The multivariable ratios of progression rates when we compared participants with cryptogenic SLD, MASLD, or MetALD with those without SLD were 0.98 (95% CI 0.95-1.01), 1.03 (95% CI 1.03-1.04), and 1.07 (95% CI 1.04-1.09), respectively. The multivariable ratios of progression rates when we compared participants with SLD with FIB-4 score <1.3 and SLD with FIB-4 score ≥1.3 with those without SLD were 1.03 (95% CI 1.02-1.04), and 1.05 (95% CI 1.04-1.06), respectively. SLD was associated with a higher risk of coronary atherosclerosis, and the risk differed by sub-classifications and severity. These findings suggest that the newly proposed definition has clinical relevance in terms of stratifying cardiovascular disease risk.

Abstract P113: Associations of Immune Cell Subsets With Coronary Artery Calcium Incidence and Progression in the Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium (CAC) and its progression strongly associates with incident cardiovascular disease (CVD). Although immune dysregulation and related inflammation are important causes of coronary artery disease, few data exist on associations between specific immune cell subsets and CAC presence and progression. Hypothesis: We hypothesized innate &amp; adaptive immune cell subsets are associated with longitudinal CAC changes Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we examined associations of immune cell subsets (measured at baseline in peripheral blood by flow cytometry) with incident CAC and CAC progression. Of 975 participants sampled who had CAC and immune cell subsets measured at baseline (2000-02), 378 had CAC 0 at baseline and were used to examine incident CAC from MESA exam 2 (2002-04) through 5 (2010-12); the remaining 597 participants were included to analyze CAC progression from exam 1-5. Incident CAC analyses (N=378) used Weighted Cox regressions to determine hazard ratios of incident CAC, adjusted for age, gender, race, MESA site, education, smoking status, blood pressure, body-mass index, diabetes status, cholesterol, HDL cholesterol, statin use, and antihypertensive medication. CAC progression analyses among individuals with nonzero CAC at baseline (N=597) used weighted multivariable-adjusted linear mixed models to investigate associations of baseline immune cell subsets with CAC progression, with Benjamini-Hochberg correction for multiple comparisons. Results: Among 378 participants with CAC 0 and immune cell subsets measured at baseline, 149 had incident CAC between MESA examination 2-5. Of 19 subsets measured, natural killer (NK) cells (CD3-CD16+CD56+) were associated with an elevated risk of incident CAC (hazard ratio (HR) 1.26 per standard deviation (SD) higher NK cells; 95% confidence interval (CI) 1.03-1.56, p=0.03). Two CD4+ T cell subsets, Th1 (HR 0.81, 95% CI 0.66-0.99, p=0.04) and Th2 (HR 0.80, 95% CI 0.64-0.99, p=0.04) were associated with a borderline lower risk for incident CAC. In analyses of CAC progression for participants with nonzero CAC at baseline (N=597), CD19+ B-cells were associated with CAC progression (beta-coefficient=53.1 Agatston units per SD higher B-cells proportion, 95% CI 2.0-104.2, p=0.04), while intermediate monocytes (CD14+CD16+) (beta = -71.6 Agatston units per SD higher, 95% CI -134.9 - -8.3, p=0.03) and higher T-regulatory cells (CD4+CD25+CD127-) (beta = -71.6 Agatston units per SD higher, 95% CI -119.1 - -4.8, p=0.03) were negatively associated with CAC progression. Conclusions: Among individuals with CAC 0 at baseline, NK cells were associated with incident CAC. In individuals with nonzero CAC at baseline, T-regulatory cells and intermediate monocytes were negatively associated with CAC progression, whereas B-cells were positively associated with CAC progression.

Abstract P336: The Association of Coronary Artery Calcium Progression and Cognitive Function in Midlife - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Little is known about the impact of coronary artery calcium (CAC) and its progression on cognitive function in midlife, a time of importance for cognitive aging. Methods: In CARDIA, CAC was measured using computed tomography at years 15 (baseline), 20 and 25. CAC progression was defined as: (1) CAC&gt;0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 0&lt;baseline CAC&lt;100; or (3) an annualized percent change (annualized change in CAC score divided by baseline CAC score) ≥10% among those with baseline CAC≥100. Cognitive function was measured with Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Interference, Montreal Cognitive Assessment (MoCA) and Verbal Fluency (Letter and Category Fluency) at year 35. We used linear regression to estimate the difference between marginal means with 95% confidence intervals (CIs) of each cognitive test by CAC score (0 vs &gt;0) and CAC progression. Results: Among 2,341 participants (mean age 40.3 ± 3.6 years, 56% female, 43% Black at baseline), higher CAC score and CAC progression were associated with significantly lower cognitive performance in all cognitive tests. After adjustment for demographics, the association remained for CAC progression, compared to no progression, for most test scores: DSST (-2.70 95% CI: -4.05 to -1.36, p &lt; 0.001), MoCA (-0.44 95% CI: -0.74 to -0.13, p = 0.005) and verbal fluency (-0.85 95% CI: -1.57 to -0.12, p = 0.02). Similar associations were observed for higher CAC score (&gt;0 vs 0): DSST (-3.11 95% CI: -5.16 to -1.06, p = 0.003), MoCA (-0.81 95% CI: -1.28 to -0.34, p = 0.001) and RAVLT (-0.67 95% CI: -1.12 to -0.23, p = 0.003). Additional adjustment for physical activity, depressive symptoms, and APOE, and mutually for baseline CAC score and progression did not materially change the association. Conclusions: CAC score and progression were associated with lower cognitive function in midlife. CAC progression may be an independent risk factor for early cognitive aging, independent of baseline CAC score and other risk factors.

Triglyceride-glucose index is an independent predictor of coronary artery calcification progression in patients with chronic kidney disease.

Coronary artery calcification (CAC) is highly prevalent in patients with chronic kidney disease (CKD) and is associated with major adverse cardiovascular events and metabolic disturbances. The triglyceride-glucose index (TyGI), a novel surrogate marker of metabolic syndrome and insulin resistance, is associated with CAC in the general population and in patients with diabetes. This study investigated the association between the TyGI and CAC progression in patients with CKD, which is unknown. A total of 1,154 patients with CKD (grades 1-5; age, 52.8 ± 11.9 years; male, 688 [59.6%]) were enrolled from the KNOWCKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The TyGI was calculated as follows: ln (fasting triglycerides × fasting glucose/2). Patients were classified into tertiles (low, intermediate, high) based on the TyGI. The primary outcome was annualized percentage change in CAC score [(percent change in CAC score + 1)12/follow-up months - 1] of ≥15%, defined as CAC progression. During the 4-year follow-up, the percentage of patients with CAC progression increased across TyGI groups (28.6%, 37.5%, and 46.2% in low, intermediate, and high groups, respectively; p < 0.001). A high TyGI was associated with an increased risk of CAC progression (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.14-3.88; p = 0.02) compared to the low group. Moreover, a 1-point increase in the TyGI was related to increased risk of CAC progression (OR, 1.55; 95% CI, 1.06-1.76; p = 0.02) after adjustment. A high TyGI may be a useful predictor of CAC progression in CKD.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. MethodsWe assessed the distribution of CVH metrics (inadequate: score 0–8, average: 9–10, optimal: 11–14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). ResultsWe included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14–0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19–0.53), p < 0.01]. ConclusionsOptimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis

Background and aimsMatrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. ResultsFor every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 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 < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. ConclusionsWe found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Longitudinal associations of the alternative healthy eating index with coronary artery calcification and pericardial adiposity in US adults with and without type 1 diabetes

Background and aimLong-term associations between the alternative healthy eating index (AHEI) score and two predictive indicators for CVD, pericardial adipose tissue (PAT) and coronary artery calcification (CAC) volume, are lacking. Our study aims to investigate the longitudinal associations of the AHEI score with measures of CAC and PAT in adults with and without type 1 diabetes (T1D). Methods and resultsThe prospective Coronary Artery Calcification in T1D (CACTI) study included 652 people with T1D and 764 people without diabetes (non-DM) (19–56 years old) and was conducted in 2000–2002, 2003–2004, and 2006–2007. At each visit, food frequency questionnaires were collected and PAT and CAC were measured using electron beam computed tomography. Two variables were used for CAC analyses: a continuous variable for the square-root tranformed volume (SRV) for each visit and a second variable identified CAC progression from baseline to visit 3. Mixed effect models and a logistic regression model were used to conduct statistical analyses. A one-point increase in the AHEI score was significantly associated with a −0.12 cm3 (95% CI: −0.17, −0.08; p-value<0.0001) decrease in PAT volume in combined analyses, a −0.16 cm3 (95% CI: −0.22, −0.09; p-value<0.0001) decrease in the non-DM group, a marginally significant −0.07 cm3 (95% CI: −0.14, 0.002; p-value = 0.0571) decrease in the T1D group, and was not associated with either CAC outcome. ConclusionThe AHEI score is inversely associated with PAT; the association revealed greater magnitude of PAT reduction in the non-DM group. The AHEI score did not associate with CAC progression.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults

Background and aimsWe aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). MethodsA total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32–46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. Results1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30–1.36), incidence (1.30–1.32), and progression (1.31–1.35) of coronary artery calcium (CAC) and a 42–44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 μm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. ConclusionsAmong adults aged 32–46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

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.

Cardiac troponins and coronary artery calcium score: a systematic review

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification.

Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple Emax model for maximum concentration (Cmax) and PD effect, and linear and non-linear Emax models for exposure-efficacy among individual average Cmax and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo (n = 15), 300mg (n = 20), or 600mg (n = 20), average Cmax across visits was not quantifiable (<0.76μM), 15μM, and 46μM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a Cmax ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple Emax models described 80% maximal effect at exposures >21.9µM and a plateau in exposure-efficacy above the third quartile of Cmax (≥32µM). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028.

Denosumab Decreases Epicardial Adipose Tissue Attenuation in Dialysis Patients with Secondary Hyperparathyroidism and Low Bone Mass

Introduction: Denosumab preceding elective surgery is an alternative option when parathyroidectomy is not immediately possible. Denosumab (an osteoprotegerin mimic) may play a role in the cardiovascular system, which is reflected in the features of epicardial adipose tissue (EAT) and coronary artery calcification (CAC). Methods: We investigated the effects of denosumab on EAT attenuation (EATat) and CAC in dialysis patients with secondary hyperparathyroidism (SHPT). This cohort study included patients on dialysis with SHPT. The baseline characteristics of dialysis patients and propensity score-matched non-dialysis patients were compared. Computed tomography scans of the dialysis patients (dialysis group with denosumab, n = 24; dialysis group without denosumab, n = 21) were obtained at baseline and at 6 months of follow-up. Results: At baseline, the dialysis group patients had a higher EATat-median (−71.00 H ± 10.38 vs. −81.60 H ± 6.03; p < 0.001) and CAC (1,223 A [248.50–3,315] vs. 7 A [0–182.5]; p < 0.001) than the non-dialysis group. At follow-up, the dialysis group without denosumab showed an increase in Agatston score (1,319.50 A [238.00–2,587.50] to 1,552.00 A [335.50–2,952.50]; p = 0.001) without changes in EATat-median (−71.33 H ± 11.72 to −70.86 H ± 12.67; p = 0.15). The dialysis group with denosumab showed no change in Agatston score (1,132.2 A [252.25–3,260.5] to 1,199.50 A [324.25–2,995]; p = 0.19) but a significant decrease of EATat-median (−70.71 H ± 9.30 to −74.33 H ± 10.28; p = 0.01). Conclusions: Denosumab may reverse EATat and retard CAC progression in dialysis patients with SHPT.

The association of lipoprotein(a) and coronary artery calcium in asymptomatic patients: a systematic review and meta-analysis.

Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a tool to diagnose subclinical atherosclerosis and guide clinical decision-making for primary prevention of CHD. Studies show conflicting results concerning the relationship between Lp(a) and CAC in asymptomatic populations. We conducted a meta-analysis to evaluate the association of Lp(a) and CAC in asymptomatic patients. We systematically searched PubMed, Embase, and Cochrane until April 2023 for studies evaluating the association between Lp(a) and CAC in asymptomatic patients. We evaluated CAC > 0 Agatston units, and CAC ≥ 100. Lp(a) was analysed as a continuous or dichotomous variable. We assessed the association between Lp(a) and CAC with pooled odds ratios (OR) adopting a random-effects model. A total of 23 105 patients from 18 studies were included in the meta-analysis with a mean age of 55.9 years, 46.4% female. Elevated Lp(a) increased the odds of CAC > 0 [OR 1.31; 95% confidence intervals (CI) 1.05-1.64; P = 0.02], CAC ≥100 (OR 1.29; 95% CI 1.01-1.65; P = 0.04; ), and CAC progression (OR 1.43; 95% CI 1.20-1.70; P < 0.01; ). For each increment of 1 mg/dL in Lp(a) there was a 1% in the odds of CAC > 0 (OR 1.01; 95% CI 1.01-1.01; P < 0.01). Our findings of this meta-analysis suggest that Lp(a) is positively associated with a higher likelihood of CAC. Higher Lp(a) levels increased the odds of CAC >0. These data support the concept that Lp(a) is atherogenic, although with high heterogeneity and a low level of certainty. CRD42023422034. Asymptomatic patients with elevated Lp(a) had 31% higher chances of having any coronary calcification (CAC > 0) and 29% higher chances of having more advanced calcification (CAC > 100). It increased the chances of having progression of coronary calcification over time by 43%. For each 1 mg/dL of Lp(a) there was an increment of 1% chance of having coronary calcification.

Immune checkpoint inhibitors in cancer: the increased risk of atherosclerotic cardiovascular disease events and progression of coronary artery calcium

BackgroundImmune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified.MethodsPatients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups.ResultsOverall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs.ConclusionsTreatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review.

Vascular calcification (VC) is a complex process of calcium deposition on the arterial wall and atherosclerotic plaques and involves interaction between vascular smooth muscle cells, inflammatory and VC mediators. The latter are independent predictors of cardiovascular morbidity and mortality and potential targets of pharmaceutical therapy. This paper is a narrative review of the complex mechanisms of VC development and in this context the potential anti-atherosclerotic effects of statins. At the initial stages of atherosclerosis VC correlates with atherosclerosis burden and in the long-term with cardiovascular morbidity and mortality. A plethora of animal and clinical studies have proposed statins as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Based on coronary computed tomography data, high doses of statins may have negligible or even positive effects on the progression of coronary artery calcification. Growing data support an increase in atherosclerotic plaque calcification in peripheral arteries (e.g., carotids), after long-term, statin-therapy. Despite the paradox of increasing VC, those effects of statins have been associated with higher plaque stability, reducing the risk of consequent adverse events. Statins seem to promote a "favorable" atherosclerotic calcification, suppressing atherosclerotic lesion expansion and their vulnerability. More studies are required to clarify the underlying mechanisms.