Progression Of Coronary Artery Calcification Research Articles

The Curious Case of Synergy between Lipoprotein (a), Coronary Calcification, and Cardiovascular Disease Risk.

Despite recent advances in cardiovascular interventions and preventive therapies, there remains a substantial residual risk of atherosclerotic cardiovascular disease (ASCVD), even among patients on maximal guideline-directed medical therapy. Growing epidemiological and genetic evidence supports the causal role that lipoprotein(a) [Lp(a)], an apolipoprotein-B–containing lipoprotein, plays in increasing the risk of ASCVD morbidity and mortality, and an elevated Lp(a) (≥50 mg/dL or ≥125 nmol/L) is considered a risk enhancer in recent national guidelines (1). Multiple proinflammatory, proatherogenic, procalcific, and cellular signaling mechanisms have been described that could mediate the association of Lp(a) with ASCVD clinical events, in particular due to the oxidized phospholipid content of Lp(a) (2). An intriguing finding has been that elevated Lp(a) concentrations do not associate with prevalent coronary artery calcification (CAC) despite being associated with more rapid progression of CAC and atherosclerotic plaque (3). But while prior studies have shown no association between prevalent Lp(a) and CAC, the joint association of Lp(a) and CAC with the risk of future ASCVD events is not well understood (4). CAC, measured on computed tomography, is an established risk enhancer incorporated into recent guidelines to favor initiation or intensification of statin therapy in patients with uncertain ASCVD risk. On the other hand, the absence of CAC has been used to favor withholding or delaying statin use in certain patients (1).

98-OR: Prediction of Cardiovascular Disease in People with Type 1 Diabetes with Novel Omics Biomarkers

Introduction: Type 1 diabetes (T1D) increases risk for cardiovascular disease (CVD) at least 2-4 fold, with only half the excess risk explained by known risk factors. We sought to identify novel proteomic, lipidomic, and metabolomic biomarkers of CVD in T1D. Methods: We first built a predictive model of coronary artery calcium progression (CACp) using LASSO regression of clinical variables measured at baseline in 365 participants with T1D in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. The selected model was refit to a subgroup of 102 participants with complete clinical information and measured omics markers (targeted and untargeted metabolomics, global proteomics, glycated proteomics, and lipidomics) . Omics biomarkers were identified for inclusion in the final model by retaining the top markers that predicted CACp by moderated t-tests and sPLS-DA models. Results: The table shows variables retained in the clinical model (AUC=0.91) and in the model with biomarkers added (AUC=0.94) . Higher age, urine albumin:creatinine, and insulin dose predicted CACp in both models. Longer duration of T1D predicted CACp in the clinical model. In the model with D-Glucosamine/D-galactosamine and glycated fibrinogen peptides, D-Glucosamine/D-Galactosamine predicted CACp. Conclusion: Novel metabolites improved prediction of CACp in people with T1D. Disclosure L.Pyle: None. T.B.Vigers: None. R.K.Johnson: None. Q.Zhang: None. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. Funding American Heart Association (17CSA33570025) , NIH (P30-DK116073)

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.

Coronary artery calcium incidence and changes using direct plaque measurements: The MASALA study

Background and aimsWe aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants. MethodsWe used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010–2013, 2016–2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models. ResultsThe study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p = 0.02), baseline volume (β +0.24 per mm3, p < 0.01), and scan interval (β +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (β +0.81 per mg/dL, p = 0.03), exercise (β +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (β +0.15 per mm3, p < 0.01) and density (β −0.55 per unit, p < 0.01) were associated with change in total density. ConclusionsIn this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density.

The impact of nonoptimal lipids on the progression of coronary artery calcification in asymptomatic young adults: results from the KOICA registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Recently, as cumulative exposure of lipids for a lifetime has become important to prevent and predict atherosclerotic cardiovascular disease (ASCVD), it is recommended to obtain the optimal lipid levels from a young age. However, questions remain regarding the vascular changes in young adulthood by nonoptimal lipid levels. Purpose We aimed to investigate the progression of coronary artery calcification (CAC) according to lipid profiles in Korean young adults. Methods From the KOrea Initiative on Coronary Artery calcification registry, we collected 2,940 statin-naïve adults under 45-year-old, undergoing serial coronary artery calcium scans for the purpose of routine health check-ups between 2002 and 2017. CAC progression was assessed according to the optimality of lipid levels and each lipid variable. Results In this cohort (mean age, 41.3 years; man 82.4%), only 477 subjects (16.2%) had the optimal lipid profile, defined as triglycerides &amp;lt;150 mg/dl, LDL cholesterol &amp;lt;100 mg/dl, and HDL cholesterol ≥45 mg/dl. During follow-up (median 39.7 months), CAC progression was observed in 438 participants (14.8%) and more frequent in nonoptimal lipid group (16.5% vs 5.9%; p&amp;lt;0.001). Nonoptimal lipid levels during young adulthood increased the risk of CAC progression after adjusting for other cardiovascular risk factors (adjusted HR, 2.36; p=0.001), with a stepwise risk increase according to lipid levels. In particular, in the subjects with an initial calcium score of zero (adjusted HR, 2.13; p=0.014), those in their 20s or 30s (adjusted HR 2.70; p=0.029), and those without any other risk factors (adjusted HR 2.51; p=0.025), deemed as very low-risk groups, nonoptimal lipid levels more than doubled the risk of CAC progression, respectively. Among lipid variables, high triglycerides appeared to provide the greatest impact on CAC progression of young adults. Conclusions The proportion of young adults with optimal lipid levels was lower than expected. Nonoptimal lipid level was significantly associated with the risk of CAC progression in young adults, even with low-risk. Triglycerides had the strongest association with the risk of CAC progression. Screening and intervention for nonoptimal lipid levels, particularly triglycerides, from an early age might be of clinical value.

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.

MO185: Post-Translational Carbamylation of Sortilin is Associated with Cardiovascular Calcification in Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Sortilin, an intracellular sorting receptor, has been identified as a cardiovascular (CV) risk factor in the general population. Patients with chronic kidney disease (CKD) are highly susceptible to developing CV complications such as CV calcification. However, specific CKD-induced post-translational protein modifications of sortilin and their link to CV calcification remain unknown. METHODS Circulating sortilin isolated from two independent CKD cohorts was analysed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF mass spectrometry). The binding partner affinity was analysed by surface plasmon resonance spectroscopy. The effect of carbamylated sortilin on vascular calcification was analysed in vitro using human coronary artery smooth muscle cells. RESULTS In CKD patients, targeted mass spectrometric analyses of circulating sortilin revealed an increase in carbamylated lysine residues with kidney function decline. Carbamylation did not affect dimer formation of sortilin assessed by mass spectrometry. We observed an increased affinity of interleukin 6 to in vitro carbamylated sortilin. Carbamylated sortilin increased SMC calcification in vitro that was accelerated by interleukin 6, while carbamylated albumin and collagen type I did not affect SMC calcification. Mass-spectrometry imaging of human calcified arteries revealed in situ carbamylated sortilin. In CKD patients, sortilin carbamylation was associated with coronary artery calcification volume, independent of age, kidney function and other risk factors. Moreover, patients with carbamylated sortilin displayed significantly faster coronary artery calcification progression than patients without sortilin carbamylation. CONCLUSION Carbamylated sortilin is a risk factor for CV calcification and may contribute to elevated CV complications in patients with CKD.

Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals

Background and aimsIncreased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression. MethodsCross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression. ResultsOf 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84–1.06) and 0.82 (0.71–0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965–0.995). ConclusionsWe found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

Deoxycholic Acid and Coronary Artery Calcification in the Chronic Renal Insufficiency Cohort.

BackgroundDeoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and progression in a large and diverse population of individuals with chronic kidney disease stages 2 to 4 is unknown.Methods and ResultsIn the CRIC (Chronic Renal Insufficiency Cohort) study, we evaluated cross‐sectional (n=1057) and longitudinal (n=672) associations between fasting serum DCA levels and computed tomographic CAC using multivariable‐adjusted regression models. The mean age was 57±12 years, 47% were women, and 41% were Black. At baseline, 64% had CAC (CAC score >0 Agatston units). In cross‐sectional analyses, models adjusted for demographics and clinical factors showed no association between DCA levels and CAC >0 compared with no CAC (prevalence ratio per 1‐SD higher log DCA, 1.08 [95% CI, 0.91–1.26). DCA was not associated with incident CAC (incidence per 1‐SD greater log DCA, 1.08 [95% CI, 0.85–1.39]) or CAC progression (risk for increase in ≥100 and ≥200 Agatston units per year per 1‐SD greater log DCA, 1.05 [95% CI, 0.84–1.31] and 1.26 [95% CI, 0.77–2.06], respectively).ConclusionsAmong CRIC study participants, DCA was not associated with prevalent, incident, or progression of CAC.

Magnesium and Zinc Intake Ratio Mediates the Increase of Coronary Artery Calcification through Upregulating Interleukin 6

ABSTRACT The relation between dietary minerals and coronary artery calcification (CAC) has been emphasized. However, the effects of multiple dietary minerals on CAC progression remain unclear. This study Investiagetes the effect of combined dietary mineral intake on the progression of CAC. We analyzed a population-based cohort with 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores were measured at baseline and subsequent follow-up examinations by Multi-detector computed tomography (MDCT) scans with Agatston scores. Then, the progression of CAC was defined through increased CAC scores in the follow-up from the baseline exam. The results revealed that the dietary intake of individual minerals did not show significant differences across CAC progression vs non progression groups. However, participants with CAC progression had an increased Magnesium (Mg):Zinc (Zn) ratio (P < 0.05). This effect was significant in logistic regression after adjusting for multiple established risk factors of CAC progression (OR 1.050; 95% CI 1.003, 1.099; P = 0.038). The increased risk of CAC associated with Mg/Zn was mediated through an increase level of IL-6, which increased with association to the Mg: Zn ratio. In conclusion, the dietary of Mg: Zn ratio, rather than individual mineral intake is associated with increased risk of CAC progression, which is mediated by pro-calcific IL-6. Therefore, the consideration of dietary intake of Zn and Mg together would play a cardio protective role among CAC patients.

Associations of long-term physical activity trajectories with coronary artery calcium progression and cardiovascular disease events: results from the CARDIA study

ObjectiveThe study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events.MethodsWe...

Relation of Progression of Coronary Artery Calcium to Dementia (from the Multi-Ethnic Study of Atherosclerosis)

Baseline coronary artery calcification has been shown to be associated with dementia. However, the value of coronary artery calcium (CAC) progression in the prediction of dementia remains unclear. In this study, we examined the association between CAC progression and dementia in the Multi-Ethnic Study of Atherosclerosis. The Multi-Ethnic Study of Atherosclerosis is a prospective study consisting of 6,814 participants 45 to 84years of age, free of overt cardiovascular disease at baseline. A total of 5,570 subjects had baseline and follow-up CAC scans approximately 2.5years apart and were included this analysis. A total of 4,173 of these participants completed cognitive testing with the Cognitive Abilities Screening Instrument (CASI) approximately 10years after the baseline CAC scan. Dementia diagnoses were identified using International Classification of Diseases codes from hospitalizations, death certificates, and medications used to treat dementia. The absolute change between baseline and follow-up CAC was used to assess CAC progression. Cox proportional hazards and multivariable linear regression models were used to examine the association of CAC progression with incident dementia and with CASI score. Over a median follow-up of 13.2 (interquartile range: 11.2 to 15.3) years, 350 participants developed incident dementia. CAC progression showed no association with dementia risk after adjustment for age, gender, race/ethnicity, vascular risk factors, and baseline CAC score. There was no association of CAC progression with CASI score in any adjusted model. In conclusion, progression of CAC over approximately 2.5years was not associated with increased risk of dementia after adjustment for demographic variables, vascular risk factors, and baseline CAC.

Abstract MP25: Physical Activity And The Progression Of Coronary Artery Calcification

Introduction: High volume endurance physical activity (PA) has been shown to associate with increased clinically relevant coronary artery calcification (CAC) but not mortality. A key issue is whether active individuals with CAC have progression of atherosclerosis in the setting of sustained high levels of PA. Hypothesis: We hypothesized that changes in CAC are not related to corresponding changes in PA volume. Further, we hypothesized the rate of CAC progression to ≥100 Agatston units (AU) does not depend on baseline PA level. Methods: The study included 6,525 men and 2,056 women with ≥2 assessments of PA and CAC (EBT scans (1997-2007) or MDCT scans (2007-2019)). All individuals had at least one follow-up visit (mean=1.8). We used mixed linear regression to relate within-person changes in square-root CAC to changes in PA volume, controlling for between-person effects. We used interval-censored proportional hazards regression to test if progression to CAC≥100 AU was related to baseline PA level: ≥3000, 1500-2999, and &lt;1500 MET·minutes/week (MET·min/wk). Covariates included age, smoking, BMI, glucose, cholesterol, systolic blood pressure, and statin use. In addition, the longitudinal analysis was adjusted for time since baseline, while the time-to-CAC-threshold analysis was adjusted for baseline CAC. Results: Mean baseline age was 50 years in men/51 years in women. Mean time to first follow-up was 4.5 years in men/5.1 years in women. PA levels increased by 100 MET·min/wk in men but were stable in women. Cardiorespiratory fitness was stable between visits. Within person changes in CAC were not associated with changes in PA volume (Table). At baseline, 5285 men and 1948 women had CAC&lt;100 AU; at follow-up, 1127 men and 136 women progressed to CAC≥100 AU. Neither PA ≥3000 nor 1500-2999 MET·min/wk exhibited significant risk of CAC progression versus &lt;1500 MET·min/wk. Estimated hazard ratios were ≤1 for both men and women. Conclusions: These results show no apparent risk of increasing CAC with sustained PA in active individuals.

Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women.

BackgroundPrevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well‐being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well‐being was associated with less progression of coronary artery calcium (CAC).Methods and ResultsParticipants were 312 women (mean age 50.8) from the SWAN (Study of Women’s Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well‐being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well‐being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well‐being was associated with less progression (RR, 0.909; 95% CI, 0.843−0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871−1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852−0.995; P=0.037).ConclusionsOptimum early prevention of CVD in women may result from including the mind side of the mind‐heart‐body continuum.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification

BackgroundKDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. MethodsIn this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. Results87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. ConclusionsThe association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

Association of Body Weight Variability With Progression of Coronary Artery Calcification in Patients With Predialysis Chronic Kidney Disease.

BackgroundWe investigated whether high body weight variability (BWV) is associated with a higher prevalence of coronary artery calcification (CAC) or more rapid progression of CAC in patients with predialysis chronic kidney disease (CKD).MethodsA total of 1,162 subjects from a nationwide prospective cohort of predialysis CKD were analyzed. The subjects were divided into the tertile (T1, T2, and T3) by BWV. CAC was assessed at the baseline and a 4-year follow-up by CT scan. Rapid progression of coronary artery calcification was defined as an increase in coronary artery calcium score (CACS) more than 200 Agatston units during a 4-year follow-up.ResultsOne-way ANOVA revealed that CACS change during the follow-up period is significantly higher in the subjects with high BWV, although CACS at the baseline and 4-year follow-up was not different among the tertile groups by BWV. Logistic regression analysis revealed that compared to low BWV (T1), both moderate (T2, adjusted odds ratio (OR) 2.118, 95% CI 1.075–4.175) and high (T3, adjusted OR 2.602, 95% CI 1.304–5.191) BWV was associated with significantly increased risk of rapid progression of CAC. Importantly, the association between BWV and progression of CAC remained robust even among the subjects without significant BW gain or loss during follow-up periods (T2, adjusted OR 2.007, 95% CI 1.011–3.984; T3, adjusted OR 2.054, 95% CI 1.003–4.207).ConclusionHigh BWV is independently associated with rapid progression of CAC in patients with predialysis CKD.

Association of High Serum Adiponectin Level With Adverse Cardiovascular Outcomes and Progression of Coronary Artery Calcification in Patients With Pre-dialysis Chronic Kidney Disease.

Background: Serum adiponectin level predicts cardiovascular (CV) outcomes and progression of coronary artery calcification (CAC) in the general population, although the association has not been validated in patients with chronic kidney disease (CKD). In this study, we investigated the association of high serum adiponectin level with the risk of adverse CV outcomes and progression of CAC in patients with pre-dialysis CKD.Methods: A total of 1,127 patients with pre-dialysis CKD from a nationwide prospective cohort of patients with pre-dialysis CKD in Korea were divided into the tertile by serum adiponectin level at the baseline. CV outcome of interest was fatal and non-fatal CV events and all-cause mortality. Progression of CAC was defined as coronary artery calcium score (CACS) change more than 200 during a 4-year follow-up.Results: Cox regression analysis revealed that high serum adiponectin is associated with increased risk of fatal and non-fatal CV events (adjusted hazard ratio 2.799, 95% CI 1.348–5.811). In contrast, high serum adiponectin level was not significantly associated with all-cause mortality (adjusted hazard ratio 0.655, 95% CI 0.203–2.113). Binary logistic regression analysis revealed that high serum adiponectin level is also associated with increased risk of progression of CAC (adjusted odds ratio [OR] 2.078, 95% CI 1.014–4.260). Subgroup analyses demonstrated that the association of high serum adiponectin with increased risk of fatal and non-fatal CV events is not modified by age, gender, history of diabetes, estimated glomerular filtration rate (eGFR), or spot urine albumin-to-creatinine ratio (ACR).Conclusions: High serum adiponectin level is associated with adverse CV outcomes and progression of CAC in patients with pre-dialysis CKD.

Statins Accelerate Coronary Calcification and Reduce the Risk of Cardiovascular Events.

Lipid-lowering therapy with statins is well recognized as an effective therapy in reducing adverse cardiovascular events. However, the relationship between statin therapy and progression of coronary artery calcification (CAC) is unclear. A few of studies suggested that statins fail to slow and even accelerate progression of CAC; meanwhile, some researchers demonstrate opposite results. With the purpose of seeking out the effect of statin therapy on CAC, we summarized the existing evidence on statins and undertook meta-analyses of clinical trials assessing the effect of statin therapy on CAC. Fourteen trials were identified suitable for inclusion in the analysis of the effect of statin treatment on CAC, of which 11 were randomized controlled trails, 1 was case-control study, 1 was cross-sectional study, and 1 was observational study. In the meta-analysis of CAC progression, statin therapy seemed to accelerate the progression of CAC. Meanwhile, the analysis revealed a significant correlation between statin treatment and lower risk of cardiovascular events. In conclusion, meta-analyses of the available trials have shown a significant reduction of risk of cardiovascular events. In contrast, statins accelerated CAC. This suggests that statin-mediated atheroma calcification may enhance plaque stability and reduce the risk of plaque rupture.

Association Between Serum Uric Acid Levels and Progression of Coronary Artery Calcification in Japanese Subjects at a Health Checkup

Association Between Serum Uric Acid Levels and Progression of Coronary Artery Calcification in Japanese Subjects at a Health Checkup

Effects of lanthanum carbonate and calcium carbonate on cardiovascular calcification in hemodialysis patients: A systematic review and meta-analysis.

This paper was written to systematically review and meta-analyze the evidence on the efficacy of lanthanum carbonate (LC) and calcium carbonate (CC) and the risk of cardiovascular calcification on hemodialysis (HD) patients. The Cochrane library, PubMed, Web of Science, Chinese journal full-text database (CNKI), WANGFANG DATA, and Sino Med were searched between January 1946 and December 2020. The literature with respect to the randomized controlled clinical trial comparing LC and CC in HD patients was selected. The main outcomes include coronary artery calcification score (CACS), cardiovascular events, and serum phosphorus (mmol/L). The statistical program used for meta-analysis was Stata V14.0. Of 388 original titles screened, data was extracted from 9 studies (625 participants). LC can significantly reduce the progression of coronary artery calcification compared to CC (standardized mean deviation (SMD) = -0.59, 95% CI: -0.94 to -0.25, p < 0.01). The LC group had lower serum phosphorus levels (SMD = -1.35, 95% CI: -2.33 to -0.36, p < 0.01), lower serum calcium levels (SMD = -1.03, 95% CI: -1.83 to -0.23, p = 0.012), and lower fibroblast growth factor 23 (FGF-23) level (SMD = -4.80, 95% CI: -7.96 to -1.64, p = 0.003) than the CC group. The Egger regression test of CACS showed no potential publication bias (p = 0.72). Compared with CC, LC can significantly delay the process of coronary artery calcification, and at the same time reduce patients' serum phosphate, serum calcium, and FGF-23. Therefore, we recommend LC as a phosphorus-lowering drug for HD patients.