Change In Coronary Artery Calcification Score Research Articles

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>0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 0<baseline CAC<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 >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 < 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 (>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.

Clinical Implication of Consistently Strict Phosphate Control for Coronary and Valvular Calcification in Incident Patients Undergoing Hemodialysis.

Serum phosphate control is crucial for the progression of vascular and valvular calcifications. Strict phosphate control is recently suggested; however, there is a lack of convincing evidence. Therefore, we explored the effects of strict phosphate control on vascular and valvular calcifications in incident patients undergoing hemodialysis. A total of 64 patients undergoing hemodialysis from our previous randomized controlled trial were included in this study. Coronary artery calcification score (CACS) and cardiac valvular calcification score (CVCS) were evaluated using computed tomography and ultrasound cardiography at baseline and 18 months after the initiation of hemodialysis. The absolute changes in CACS (ΔCACS) and CVCS (ΔCVCS) and the percent change in CACS (%ΔCACS) and CVCS (%ΔCVCS) were calculated. Serum phosphate level was measured at 6, 12, and 18 months after the initiation of hemodialysis. Moreover, phosphate control status was evaluated using the area under the curve (AUC) by the amount of time spent with a serum phosphate level of ≥ 4.5 mg/dL and the extent to which this threshold exceeded over the observation period. ΔCACS, %ΔCACS, ΔCVCS, and %ΔCVCS were significantly lower in the low AUC group than in the high AUC group. ΔCACS and %ΔCACS were also significantly lower. ΔCVCS and %ΔCVCS tended to be lower in patients whose serum phosphate level never exceeded 4.5 mg/dL than in those whose serum phosphate level continuously exceeded 4.5 mg/dL. AUC significantly correlated with ΔCACS and ΔCVCS. Consistently strict phosphate control may slow the progression of coronary and valvular calcifications in incident patients undergoing hemodialysis.

Association of apolipoproteins C-I and C-II truncations with coronary heart disease and progression of coronary artery calcium: Multi-Ethnic Study of Atherosclerosis

Background and aimsHigher truncated-to-native proteoform ratios of apolipoproteins (apo) C-I (C-I’/C-I) and C-II (C-II’/C-II) are associated with less atherogenic lipid profiles. We examined prospective relationships of C-I’/C-II and C-II’/C-II with coronary heart disease (CHD) and coronary artery calcium (CAC). MethodsApoC-I and apoC-II proteoforms were measured by mass spectrometry immunoassay in 5790 MESA baseline plasma samples. CHD events (myocardial infarction, resuscitated cardiac arrest, fatal CHD, n = 434) were evaluated for up to 17 years. CAC was measured 1–4 times over 10 years for incident CAC (if baseline CAC = 0), and changes (follow-up adjusted for baseline) in CAC score and density (if baseline CAC>0). ResultsC-II’/C-II was inversely associated with CHD (n = 434 events) after adjusting for non-lipid cardiovascular risk factors (Hazard ratio: 0.89 [95% CI: 0.81–0.98] per SD), however, the association was attenuated after further adjustment for HDL levels (0.93 [0.83–1.03]). There was no association between C-I’/C-I and CHD (0.98 [0.88–1.08]). C-II’/C-II was positively associated with changes in CAC score (3.4% [95%CI: 0.6, 6.3]) and density (6.3% [0.3, 4.2]), while C-I’/C-I was inversely associated with incident CAC (Risk ratio: 0.89 [95% CI: 0.81, 0.98]) in fully adjusted models that included plasma lipids. Total apoC-I and apoC-II concentrations were not associated with CHD, incident CAC or change in CAC score. ConclusionsIncreased apoC-II truncation was associated with reduced CHD, possibly explained by differences in lipid metabolism. Increased apoC-I and apoC-II truncations were also associated with less CAC progression and/or development of denser coronary plaques.

Abstract 10296: Relation of Lipoprotein(a) to Progression of Coronary Artery Calcium: Results From a Pooled Cohort of Mesa, Cardia, and Framingham Offspring Studies

Background: Lipoprotein(a) [Lp(a)] levels and coronary artery calcium (CAC) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Progression of CAC is also associated with greater ASCVD risk. Less well-established is the relation of Lp(a) with progression of atherosclerosis as assessed by progression of CAC. Methods: We included a pooled cohort of 9454 persons without ASCVD at baseline (mean age 55.6 years, 53.5% female, and 31% black) and with multiple measures of CAC (up to 4 over a mean of 7.3 + 3.3 years from baseline CAC measures) from the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Framingham Offspring Studies. Lp(a) was assessed continuously and by category (&lt;15 mg/dL [reference], 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL) in relation to progression of CAC (annualized change in Agatston score) incorporating multiple CAC measures utilizing mixed model regression with time (in years), adjusted for age, sex, race, baseline CAC, and other covariates. Subgroup analyses were done separately in those with baseline CAC. Results: A 50 mg/dL increment of Lp(a) was associated with an adjusted annualized change in CAC score of 3.97 units. Compared to those with Lp(a) levels of &lt;15 mg/dL, those with levels of 50-69 mg/dL, 70-89 mg/dL, and &gt; 90 mg/dL had a statistically significant annualized progression of CAC that was 3.09, 8.70, and 9.46 units greater in adjusted analyses. Progression was greater in those with baseline CAC&gt;0 (Table). Conclusions: Higher levels of Lp(a) are associated with greater progression of atherosclerosis as measured by CAC scores.

The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study.

BackgroundDecreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study.MethodsIn the principal study, patients with CAC scores of 1–999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry.ResultsA total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = –0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28–6.49, p = 0.01).ConclusionsLow numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.

MO750: Dialysate Magnesium Impact on Progression of Coronary Artery Calcification

Abstract BACKGROUND AND AIMS The development of vascular calcifications is accelerated in dialysis patients and is associated with an increased risk of cardiovascular morbidity and mortality. Studies have shown that magnesium (Mg) reduces mineral deposit formation, thus potentially abating the process of vascular calcification. Therefore, the use of higher dialysate-Mg might present a promising tool to reduce vascular calcification. Many in vitro studies have investigated effects of Mg on vascular calcification, but prospective clinical trials are lacking. This study evaluated the difference in coronary artery calcification progression over 12 months based on different concentrations of routinely used dialysate-Mg. METHOD This prospective randomized, multicentre study included 60 angina-free chronic haemodialysis (HD) patients distributed into two equal groups based on dialysate-Mg level (0.5 versus 1.0 mmol/L) used routinely before and throughout the study period. Laboratory measurements, including total serum Mg level and coronary artery calcium score (CACS) determined by cardiac computed tomography, were performed in all patients at baseline and after 12 months of follow-up. RESULTS Total serum Mg was significantly higher in patients on higher dialysate-Mg, both at baseline and after 12 months of follow-up (P &amp;lt; 0.001). Nevertheless, in both study groups, total serum Mg decreased after 12 months of follow-up; from 1.13 ± 0.15 mmol/L to 0.99 ± 0.14 mmol/L (P &amp;lt; 0.001) in the lower dialysate-Mg group and from 1.39 ± 0.22 mmol/L to 1.29 ± 0.21 mmol/L (P &amp;lt; 0.001) in the higher dialysate-Mg group. CACS increased significantly in both study groups after 12 months: from 361.90 ± 725.67 to 480.00 ± 783.53 (P &amp;lt;0.001) in the lower dialysate-Mg group and from 437.71 ± 573.77 to 589.07 ± 682.82 (P &amp;lt; 0.001) in the higher dialysate-Mg. Still, the mean change in CACS (ΔCACS) did not differ significantly between the study groups (109.29 ± 181.99 versus 151.86 ± 211.22; P = 0.321). In patients with CACS = 0 at the beginning of the study (4 in the lower and 5 in the higher dialysate-Mg group), the mean ΔCACS was 21.25 ± 3.96 and 0 (P = 0.180), respectively. CONCLUSION Routine use of higher dialysate-Mg (1.0 mmol/L) increases total serum Mg level compared with standard dialysate-Mg solutions (0.5 mmol/L). However, this was not associated with lower CACS progression over 12 months of follow-up. Further research is needed to assess if patients with CACS = 0 may benefit from higher dialysate-Mg in terms of reduced calcification progression compared with standard dialysate-Mg solutions.

Abstract P126: Comparing Cardiovascular Risk Factor Progression Between South Asian Men and Women With Diabetes: A Longitudinal Analysis From the Masala Study

Introduction: South Asians have a high incidence of type 2 diabetes(DM) and cardiovascular disease (CVD). Women with DM may have greater CVD risk compared to men with DM and women without DM. No study has determined whether the incidence or progression of coronary artery calcium (CAC) score, a measure of atherosclerosis burden, differs between South Asian men and women with DM. Hypothesis: We hypothesize that CAC progression is greater in women with DM as compared to men with DM and women without DM. Methods: We used the data from the MASALA study, a community-based prospective cohort of South Asians from 2 clinical sites without CVD at baseline. We conducted a longitudinal analysis of diabetic participants who were reassessed after 5 years and compared with those without diabetes. We classified incident CAC as any CAC at exam 2 in a participant who had no CAC at baseline. To examine the progression of CVD risk factors over time, we compared change in CAC score, waist circumference, systolic and diastolic blood pressure, HbA1c and lipid levels amongst the diabetic and non-diabetic population by sex. We conducted multivariable linear regression models stratified by diabetes status to determine whether sex was independently associated with change in CAC score and other CVD risk factors. Results: Of 749 participants who were seen in follow-up, 176 (23%) had diabetes at baseline, 65% were men, and mean age was 58 years. Approximately 64% women with DM vs. 28% men with DM had CAC=0, and men had higher median CAC score (49 (IQR 0-247) vs. 0 (IQR 0-46, p&lt;0.001). After mean follow-up of 4.8±0.8 years, incident CAC did not differ between men and women with diabetes (p=0.85). Progression of CAC was greater in men with DM (94, IQR 13-290) compared to women with DM (0, IQR 0-30) (p &lt;0.001). Baseline statin and aspirin use was lower in women with DM (statins: 37% in women vs. 56% in men, p&lt;0.001; aspirin 16% in women vs. 43% in men, p&lt;0.001). In multivariable models, the fold-change in CAC in women (0.22, 95% CI 0.10 - 0.47) was lower than in men (4.54, 95% CI 2.08 - 9.89) and comparable to women without DM (0.30 95%CI 0.21 -0.43), after adjusting for age, baseline CAC, systolic and diastolic blood pressure, total and LDL cholesterol, duration of diabetes, smoking and any medication use (statin, diabetes, or hypertension med). Sex was not associated with change in any CVD risk factor among those with diabetes; but women without DM had greater change in total and LDL cholesterol and waist circumference than men without DM. Conclusion: In this South Asian population, change in CAC score was lower in women with DM than in men with DM, and was comparable to women without DM. These results suggest among South Asians with DM, overall CVD risk may be greater in men than in women.Continued follow-up of the MASALA cohort will determine whether there are sex differences in CVD outcomes.

Coronary Artery Calcium From Early Adulthood to Middle Age and Left Ventricular Structure and Function.

Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25. Results At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (β=1.218; adjusted P=0.007), higher LV end-diastolic volume (β=0.811; adjusted P=0.007), higher LV end-systolic volume (β=0.350; adjusted P=0.048), higher left atrial volume (β=0.214; adjusted P=0.009), and higher E/e' ratio (β=0.059; adjusted P=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (β=4.789; adjusted P<0.001), but not in whites (β=1.051; adjusted P=0.283). Conclusions Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.

A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD.

Developing strategies for managing coronary artery calcification (CAC) in patients with CKD is an important clinical challenge. Experimental studies have demonstrated that magnesium inhibits vascular calcification, whereas the uremic toxin indoxyl sulfate aggravates it. To assess the efficacy of magnesium oxide (MgO) and/or the oral carbon adsorbent AST-120 for slowing CAC progression in CKD, we conducted a 2-year, open-label, randomized, controlled trial, enrolling patients with stage 3-4 CKD with risk factors for CAC (diabetes mellitus, history of cardiovascular disease, high LDL cholesterol, or smoking). Using a two-by-two factorial design, we randomly assigned patients to an MgO group or a control group, and to an AST-120 group or a control group. The primary outcome was percentage change in CAC score. We terminated the study prematurely after an interim analysis with the first 125 enrolled patients (of whom 96 completed the study) showed that the median change in CAC score was significantly smaller for MgO versus control (11.3% versus 39.5%). The proportion of patients with an annualized percentage change in CAC score of ≥15% was also significantly lower for MgO compared with control (23.9% versus 62.0%). However, MgO did not suppress the progression of thoracic aorta calcification. The MgO group's dropout rate was higher than that of the control group (27% versus 17%), primarily due to diarrhea. The percentage change in CAC score did not differ significantly between the AST-120 and control groups. MgO, but not AST-120, appears to be effective in slowing CAC progression. Larger-scale trials are warranted to confirm these findings.

Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study.

Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use. From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = -0.194, P = 0.026). In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins.

The effect of magnesium supplementation on vascular calcification in chronic kidney disease—a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale

IntroductionChronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease and mortality, which is thought to be caused by increased propensity towards vascular calcification (VC). Magnesium (Mg)...

Effects of Low-density Lipoprotein Cholesterol on Coronary Artery Calcification Progression According to High-density Lipoprotein Cholesterol Levels

Previous studies reported that many patients are at high risk for cardiovascular disease (CVD) despite achieving recommended low-density lipoprotein cholesterol (LDL-C) levels. Therefore, we investigated whether the association between LDL-C and the risk for incident CVD differed according to high-density lipoprotein cholesterol (HDL-C) levels using coronary artery calcium score (CACS) progression as a surrogate marker for predicting CVD. We investigated 2132 Korean men in a health screening program, in which CACS was measured at baseline and after 4years. Coronary artery calcification (CAC) progression was defined as a change in CACS ≥0 over 4years. We divided the subjects into nine groups according to baseline HDL-C and LDL-C levels and compared their risks for CAC progression. After 4years, 475 subjects (22.3%) exhibited CAC progression. We identified a positive relationship between baseline LDL-C levels and the risk for incident CAC. However, this association was attenuated by high baseline HDL-C levels. Multivariate logistic regression analysis adjusted for age, body mass index, systolic blood pressure, fasting glucose, smoking, and exercise status revealed that the odds ratios for incident CAC in the lowest HDL-C tertile were 3.08 for LDL-C tertile 3 and 2.02 for LDL-C tertile 2 compared to LDL-C tertile 1. However, these differences disappeared in the highest HDL-C tertile (HDL-C ≥54.0mg/dL). In this longitudinal study, we found that the positive relationship between LDL-C and the relative risk for incident CAC was attenuated by higher HDL-C levels. Therefore, HDL-C levels should be considered when estimating CVD risk.

Abstract P370: Risk Factors for Progression of Coronary Artery Calcification in Patients with Chronic Kidney Disease

Introduction: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and predicts the risk of cardiovascular disease (CVD). Risk factors for the progression of CAC in patients with CKD have not been well studied. Hypothesis: We assessed the hypothesis that several established and novel CVD risk factors are associated with progression of CAC among patients with CKD. Methods: In a random subsample of 1,123 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured at baseline and the follow-up visit using electron beam computed tomography (CT) or multidetector CT. CAC progression was defined as an increase of Agatston score ≥100 units during follow-up. Multiple logistic regression and mixed-effects regression models were used to assess risk factors for progression of CAC. Results: Over an average of 3-year follow-up, 332 (29.6%) participants developed CAC progression. After adjusting for age, sex, race, clinical site, total cholesterol, HDL-cholesterol, systolic blood pressure, antihypertensive treatment, diabetes, and current smoking in the multivariable models, history of CVD (odds ratio [OR] 1.53, 95% CI 1.09-2.15, p=0.02), lipid-lowering treatment (OR 1.81, 95% CI 1.28-2.55, p&lt;0.001), higher serum phosphate (OR 1.37, 95% CI 1.17-1.61, p&lt;0.001), hemoglobin A1c (OR 1.32, 95% CI 1.10-1.58, p=0.002), and cystatin C (OR 1.24, 95% CI 1.06-1.45, p=0.007), and lower estimated-glomerular filtration rate (eGFR) (OR 1.32, 95% CI 1.10-1.56, p=0.002) were associated with CAC progression. In addition, lower physical activity, lipid-lowering treatment, body-mass index, LDL-cholesterol, lower serum calcium, phosphate, total parathyroid hormone, fibrinogen, interleukin-6, tumor necrosis factor-α, fibroblast growth factor-23, lower eGFR, cystatin C, and 24-hour urine albumin were associated with square root transformed change in CAC score from baseline in multiple-adjusted models. These findings persisted after additional adjustment for baseline CAC score. Conclusions: In conclusion, these data suggest that reduced kidney function, calcium and phosphate metabolic disorders and inflammation, in addition to established CVD risk factors, might play a role in CAC progression among patients with CKD.

Abstract MP079: Coronary Artery Calcium Incidence and Progression Among South Asians: Results From the MASALA Study

Background: South Asians have a high burden of cardiovascular disease. We have reported that South Asians have similarly high prevalence of coronary artery calcium (CAC) compared to non-Hispanic Whites, and higher CAC than other U.S. ethnic minority groups. No studies have determined the incidence or progression of CAC among South Asians. Methods: We used data from a community-based cohort of South Asians (MASALA) and calculated change in CAC Agatston score between Exam 1 (2010-2013) and Exam 2 (2015-2016) among 379 South Asians. We calculated the average annual incident CAC for those with no CAC at Exam 1, and CAC progression among those with CAC at Exam 1. We compared these findings to the previously reported CAC incidence and progression in the Multi-Ethnic Study of Atherosclerosis (MESA). We also determined factors associated with a ≥100 change in CAC score. Results: We used data from 240 men and 139 women with repeat CAC measured after 4.5±0.7 years of follow-up. Among those with no detectable CAC at baseline, 6.8% developed incident CAC annually (9.2% of men and 4.4% of women), which was similar to MESA race/ethnic groups. Among those with known CAC at baseline, the median annual CAC progression was 23 (interquartile range, 8-56). The table shows the distribution of annual CAC progression. South Asians overall, but particularly South Asian men, had significantly higher annual CAC progression compared to the reported average in MESA (overall median 18, 4-53). Established risk factors (age, male sex, diabetes and hypertension), pericardial fat volume and visceral fat area were associated with greater CAC progression. Conclusions: These preliminary results suggest that South Asian men have significantly greater CAC progression compared to other race/ethnic groups. Longer follow-up of MASALA will determine whether CAC score or CAC progression are important predictors of cardiovascular disease events.

Increased risk of coronary artery calcification progression in subjects with high baseline Lp(a) levels: The Kangbuk Samsung Health Study

BackgroundResults from previous studies support the association of lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we analyzed the association between baseline Lp(a) levels and future progression of coronary artery calcification (CAC) in apparently healthy Korean adults. MethodsA total of 2611 participants (mean age: 41years, 92% mend) who underwent a routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a) was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC was defined as a change in CACS >0 over four years. ResultsBivariate correlation analyses with baseline Lp(a) and other metabolic parameters revealed age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive correlation, while body weight, fasting glucose level, blood pressure and triglyceride level were negatively correlated with baseline Lp(a) level. After four years of follow-up, 635 subjects (24.3%) had CAC progression. The participants who had CAC progression were older, composed of more men, more obese, and had higher fasting glucose levels and worse baseline lipid profiles compared to those who did not have CAC progression. The mean serum Lp(a) level was significantly higher in subjects who had CAC progression compared to those who did not (32.5 vs. 28.9mg/dL, p<0.01). When the risk for CAC progression according to baseline Lp(a) was calculated, those with Lp(a) level≥50mg/dL had an odds ratio of 1.333 (95% CI 1.027–1.730) for CAC progression compared to those with Lp(a)<50mg/dL after adjusting for confounding factors. ConclusionsIn this study, the subjects who had higher Lp(a) were at significantly higher risk for CAC progression after four years of follow-up, suggesting the role of high Lp(a) in CAC progression.

Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study.

Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown. This study investigated the longitudinal association between NAFLD and CAC score. This study is a longitudinal cohort study performed in a healthcare center. Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography. CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed. More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043). NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

Inflammatory/Hemostatic Biomarkers and Coronary Artery Calcium Progression in Women at Midlife (from the Study of Women's Health Across the Nation, Heart Study)

It is unknown whether inflammatory/hemostatic biomarkers are associated with coronary artery calcium (CAC) progression. Our purpose was to evaluate the associations of baseline levels of C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen, and circulating factor VII with CAC progression in healthy midlife women. Inflammatory/hemostatic biomarkers were measured at baseline. CAC was quantified by computed tomography scans at baseline and after 2.3 ±0.5years of follow-up. Significant CAC progression was defined as present if (1) follow-up CAC Agatston score was >0 if baseline CAC score= 0; (2) annualized change in CAC score was ≥10 if baseline CAC score >0 to <100; and (3) annualized percent change in CAC score was ≥10% if baseline CAC score ≥100. Extent of CAC progression was defined as [log(CAC(follow-up)+25)- log(CAC(baseline)+25)]/year. Logistic and linear regression models were used as appropriate, and the final models were adjusted for baseline CAC score, age, study site, race/ethnicity, menopausal status, sociodemographics, traditional cardiovascular disease (CVD) risk factors, family history of CVD, and CVD medication use. The study included 252 women (baseline age 51.2 ± 2.6years; 67.5% white; 56.4% premenopausal or early perimenopausal). In final models, only log(PAI-1) was associated with presence of CAC progression (odds ratio 1.91, 95% CI 1.24 to 2.93; per 1 log unit increase in PAI-1; p= 0.003). In addition, higher log(PAI-1) was marginally associated with greater extent of CAC progression (p= 0.06). In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CVD risk factors.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Association between serum gamma-glutamyltransferase and the progression of coronary artery calcification

BackgroundElevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with coronary artery calcification (CAC). CAC progression is an important marker of atherosclerosis and correlates with future cardiovascular risk. However, there is a lack of research that directly examines the association between serum GGT and CAC progression. The aim of this study was to elucidate the association between serum GGT activity and CAC progression. MethodsWe enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. To eliminate the dependence of the inter scan variability on the baseline CAC scores, square root-transformed CAC scores were used to analyze CAC progression. In addition, the annualized rate of change in CAC scores was computed. ResultsSerum GGT activities were significantly higher in “progressors” than “nonprogressors”. The prevalence of progression increased with the GGT tertile (11.9%, 20.1% and 27.9% in the 1st, 2nd, and 3rd GGT tertiles, respectively; p < 0.001). In the multivariate logistic regression analysis, the odds ratio (95% confidence interval) for CAC score progression was 1.85 (1.14–3.00) in the highest GGT tertile group. By multivariate linear regression analysis, baseline serum GGT activity demonstrated a positive association with the annualized change in CAC score (β = 0.002; p = 0.006) after adjusting for cardiovascular risk factors. ConclusionElevated serum GGT levels are independently associated with CAC progression. Serum GGT levels may be a potential biomarker of future coronary atherosclerosis and prognosis.