Association of diabetes with cardiovascular calcification and all-cause mortality in end-stage renal disease in the early stages of hemodialysis: a retrospective cohort study.

BACKGROUND: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis. METHODS: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves. RESULTS: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds. CONCLUSIONS: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.

The predictive value of lesion-specific pericoronary fat attenuation index for major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The purpose of this study was to explore the prognostic significance of the lesion-specific pericoronary fat attenuation index (FAI) in forecasting major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). METHODS: This study conducted a retrospective analysis of 304 patients diagnosed with T2DM who underwent coronary computed tomography angiography (CCTA) in our hospital from December 2011 to October 2021. All participants were followed for a period exceeding three years. Detailed clinical data and CCTA imaging features were carefully recorded, encompassing lesion-specific pericoronary FAI, FAI of the three prime coronary arteries, features of high-risk plaques, and the coronary artery calcium score (CACS). The MACE included in the study comprised cardiac death, acute coronary syndrome (which encompasses unstable angina pectoris and myocardial infarction), late-phase coronary revascularization procedures, and hospital admissions prompted by heart failure. RESULTS: Within the three-year follow-up, 76 patients with T2DM suffered from MACE. The lesion-specific pericoronary FAI in patients who experienced MACE was notably higher compared to those without MACE (-84.87 ± 11.36 Hounsfield Units (HU) vs. -88.65 ± 11.89 HU, p = 0.016). Multivariate Cox regression analysis revealed that CACS ≥ 100 (hazard ratio [HR] = 4.071, 95% confidence interval [CI] 2.157-7.683, p < 0.001) and lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.400, 95% CI 1.399-4.120, p = 0.001) were independently associated with heightened risk of MACE in patients with T2DM over a three-year period. Kaplan-Meier analysis showed that patients with higher lesion-specific pericoronary FAI were more likely to develop MACE (p = 0.0023). Additionally, lesions characterized by higher lesion-specific pericoronary FAI values were found to have a greater proportion of high-risk plaques (p = 0.015). Subgroup analysis indicated that lesion-specific pericoronary FAI higher than - 83.5 HU (HR = 2.017, 95% CI 1.143-3.559, p = 0.015) was independently correlated with MACE in patients with T2DM who have moderate to severe coronary calcification. Moreover, the combination of CACS ≥ 100 and lesion-specific pericoronary FAI>-83.5 HU significantly enhanced the predictive value of MACE in patients with T2DM within 3 years. CONCLUSIONS: The elevated lesion-specific pericoronary FAI emerged as an independent prognostic factor for MACE in patients with T2DM, inclusive of those with moderate to severe coronary artery calcification. Incorporating lesion-specific pericoronary FAI with the CACS provided incremental predictive power for MACE in patients with T2DM.

Current applications, procedural and 1-year outcomes of Rotatripsy for the treatment of calcified coronary lesions.

BACKGROUND: Intravascular lithotripsy (IVL) combined with rotational atherectomy (RA), known as Rotatripsy, is used to treat severe coronary artery calcification (CAC), though data on efficacy, midterm safety and use sequence is limited. We aimed to identify indicators for Rotatripsy use and to assess its safety and success rates, both acutely and at 1-year follow-up. METHODS: Patients undergoing Rotatripsy for severe CAC across six centers from May 2019 to December 2023 were included. Demographic, clinical, procedural and follow-up data were collected. Efficacy endpoints included device success (delivery of the RA-burr and IVL-balloon across the target lesion and administration of therapy without related complications), technical success (TIMI 3 flow and residual stenosis <30% by quantitative coronary analysis) and procedural success [composite of technical success with absence of in-hospital major adverse cardiovascular events (MACE: cardiac death, myocardial infarction or target vessel revascularization). Safety endpoints comprised Rotatripsy-related complications and MACE at 1-year follow-up. RESULTS: A total of 114 patients (75 ± 9 years, 78% male) underwent Rotatripsy for 120 lesions. In the majority of procedures RA was followed by IVL, mostly electively (n = 68, 57%) but also for balloon underexpansion (n = 37, 31%) and stent crossing failure (n = 1, 1%). Diverse and complex target lesions were addressed with an average SYNTAX score of 24.6 ± 13.0. Device, technical and procedural success were 97%, 94% and 93%, respectively. Therapy-related complications included two (2%) coronary perforations, one (1%) coronary dissection and one (1%) burr entrapment. At 1-year follow-up(present in 77(67%) patients), MACE occurred in 7(9%) cases. CONCLUSIONS: Over a 1-year follow-up period, Rotatripsy was safe and effective, predominantly using RA electively before IVL.

Intravascular imaging-guided percutaneous coronary intervention for heavily calcified coronary lesions: a systematic review and meta-analysis.

Although multiple randomized clinical trials (RCTs) have shown that intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes compared with angiography-guided PCI, its benefits specifically in calcified coronary lesions is unclear due to the small number of patients included in individual trials. We performed a meta-analysis of RCTs to investigate benefits of IVI-guided PCI compared with angiography-guided PCI in heavily calcified coronary lesions. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, target-vessel or target-lesion myocardial infarction, and target-vessel or target lesion revascularization. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by using a random-effects meta-analysis based on the restricted maximum likelihood method. A search PubMed, EMBASE, and Cochrane Library from their inception to January 2024 identified 4 trials that randomized 1319 patients with angiographically moderate or severe or severe coronary calcification to IVI-guided (n = 702) vs. angiography-guided PCI (n = 617). IVI-guided PCI resulted in a significantly lower odds of MACE (OR 0.57, 95% CI 0.40-0.80) compared with angiography-guided PCI at a weighted median follow-up duration of 27.3 months. There was no evidence of heterogeneity among the studies (I2 = 0.0%), and included trials were judged to be low risk of bias. Compared with angiography-guided PCI, IVI-guided PCI was associated with a significantly lower MACE in angiographically heavily calcified coronary lesions.

Correlation Between Calcium Scoring and Abdominal Aortic Aneurysm Endovascular Repair Outcomes.

OBJECTIVES: Endovascular aneurysm repair, though minimally invasive and has the benefit of relatively low perioperative complication rates, it is associated with significant long term reintervention rates related to endoleaks. Several variables have been studied to predict the outcomes of endovascular aneurysm repair, 1 of which is the calcium burden of the vasculature. This prompted us to study the association between calcium burden measured by the standardized Agatston scoring system and the outcomes of Endovascular aneurysm repair. METHODS: This is a retrospective study of patients who underwent Endovascular aneurysm repair from 2008 to 2020 at our institution and who had a non-contrast computerized tomography scan preoperatively, accounting for 87 patients. The calcium burden of the vasculature was measured by the Agatston scoring system allowing for better reproducibility, and the outcome variables included mortality and endoleaks. RESULTS: Patients with higher median total calcium scores (≥12966.9) had significantly lesser survival (79.8% vs 52.3% (P = .002) at five years compared to patients with lower median total calcium score (<12966.9). Also, patients with type 2 endoleaks had higher calcium scores in above the aneurysm level ((1591.2 vs 688.2), P = .05)) compared to patients with no type 2 endoleaks. CONCLUSION: Calcium score assigned using a standardized Agatston scoring system can be used as a predictor of mortality risk assisting in deciding the treatment of choice for patients.

Quantitative Abdominal Arterial Calcification Correlates with Kidney Transplant Waitlist Mortality.

INTRODUCTION: The scarcity of available organs for kidney transplantation has resulted in a substantial waiting time for patients with end-stage kidney disease. This prolonged wait contributes to an increased risk of cardiovascular mortality. Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, and it is common among candidates for kidney transplant. The aim of this study was to correlate abdominal arterial calcification (AAC) score value with mortality on the waitlist. METHODS: We modified the coronary calcium score and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were listed for kidney transplant, between 2005 and 2015, and had abdominal computed tomography scan. Patients were divided into two groups: those who died on the waiting list group and those who survived on the waiting list group. RESULTS: Each 1,000 increase in the AAC score value of the sum score of the abdominal aorta, bilateral common iliac, bilateral external iliac, and bilateral internal iliac was associated with increased risk of death (HR 1.034, 95% CI: 1.013, 1.055) (p = 0.001). This association remained significant even after adjusting for various patient characteristics, including age, tobacco use, diabetes, coronary artery disease, and dialysis status. CONCLUSION: The study highlights the potential value of the AAC score as a noninvasive imaging biomarker for kidney transplant waitlist patients. Incorporating the AAC scoring system into routine imaging reports could facilitate improved risk assessment and personalized care for kidney transplant candidates.

Independent Associations of Aortic Calcification with Cirrhosis and Liver Related Mortality in Veterans with Chronic Liver Disease.

INTRODUCTION: Abdominal aortic calcifications (AAC) are incidentally found on medical imaging and useful cardiovascular burden approximations. The Morphomic Aortic Calcification Score (MAC) leverages automated deep learning methods to quantify and score AACs. While associations of AAC and non-alcoholic fatty liver disease (NAFLD) have been described, relationships of AAC with other liver diseases and clinical outcome are sparse. This study's purpose was to evaluate AAC and liver-related death in a cohort of Veterans with chronic liver disease (CLD). METHODS: We utilized the VISN 10 CLD cohort, a regional cohort of Veterans with the three forms of CLD: NAFLD, hepatitis C (HCV), alcohol-associated (ETOH), seen between 2008 and 2014, with abdominal CT scans (n = 3604). Associations between MAC and cirrhosis development, liver decompensation, liver-related death, and overall death were evaluated with Cox proportional hazard models. RESULTS: The full cohort demonstrated strong associations of MAC and cirrhosis after adjustment: HR 2.13 (95% CI 1.63, 2.78), decompensation HR 2.19 (95% CI 1.60, 3.02), liver-related death HR 2.13 (95% CI 1.46, 3.11), and overall death HR 1.47 (95% CI 1.27, 1.71). These associations seemed to be driven by the non-NAFLD groups for decompensation and liver-related death [HR 2.80 (95% CI 1.52, 5.17; HR 2.34 (95% CI 1.14, 4.83), respectively]. DISCUSSION: MAC was strongly and independently associated with cirrhosis, liver decompensation, liver-related death, and overall death. Surprisingly, stratification results demonstrated comparable or stronger associations among those with non-NAFLD etiology. These findings suggest abdominal aortic calcification may predict liver disease severity and clinical outcomes in patients with CLD.

Pedal medial arterial calcification influences the outcomes of isolated infra-malleolar interventions for chronic limb-threatening ischemia.

OBJECTIVE: Inframalleolar disease is present in most diabetic patients presenting with tissue loss. Inframalleolar (pedal) artery disease and pedal medial arterial calcification (pMAC) are associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). This study aimed to examine the impact of pMAC on the outcomes after isolated inframalleolar (pedal artery) interventions. METHODS: A database of lower extremity endovascular intervention for patients with tissue loss between 2007 and 2022 was retrospectively queried. Patients with CLTI were selected, and those undergoing isolated inframalleolar intervention on the dorsalis pedis and medial and lateral tarsal arteries and who had foot x-rays were identified. X-rays were assessed blindly for pMAC and scored on a scale of 0 to 5. Patients with concomitant superficial femoral artery and tibial interventions were excluded. Intention to treat analysis by the patient was performed. Amputation-free survival (survival without major amputation) was evaluated. RESULTS: A total of 223 patients (51% female; 87% Hispanic; average age, 66 years; 323 vessels) underwent isolated infra-malleolar intervention for tissue loss. All patients had diabetes, 96% had hypertension, 79% had hyperlipidemia, and 63% had chronic renal insufficiency (55% of these were on hemodialysis). Most of the patients had Wound, Ischemia, and foot Infection (WIfI) stage 3 disease and had various stages of pMAC: severe (score = 5) in 48%, moderate (score = 2-4) in 31%, and mild (score = 0-1) in 21% of the patients. Technical success was 94%, with a median of one vessel treated per patient. All failures were in severe pMAC. Overall, major adverse cardiovascular events was 0.9% at 90 days after the procedure. Following the intervention, most patients underwent a planned forefoot amputation (single digit, multiple digits, ray amputation, or trans-metatarsal amputation). WIfI ischemic grade was improved by 51%. Wound healing at 3 months was 69%. Those not healing underwent below-knee amputations. The overall 5-year amputation-free survival rate was 35% ± 9%. The severity of pMAC was associated with decreased AFS. CONCLUSIONS: Increasing severity of pMAC influences the technical and long-term outcomes of infra-malleolar intervention in diabetes. Severe pMAC is associated with amputation and should be considered as a variable in the shared decision-making of diabetic patients with CLTI.

Absolute iron deficiency, coronary artery calcification and cardiovascular mortality in maintenance haemodialysis patients.

AIM: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD). METHODS: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed. RESULTS: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05). CONCLUSION: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Effects of overhydration, Kt/Vurea, ß2-microglobulin on coronary artery calcification and mortality in haemodialysis patients.

AIM: We studied the effects of overhydration (OH), Kt/Vurea and ß2-microglobulin (ß2-MG) on coronary artery calcification and mortality in patients undergoing haemodialysis (HD). METHODS: The Agatston coronary artery calcium score (CACS), postdialysis body composition using bioimpedance analysis, single-pool Kt/Vurea and predialysis ß2-MG at baseline were assessed and followed up for 3 years in patients undergoing HD. We performed logistic regression analyses for a CACS ≥400 and Cox proportional hazard analyses for all-cause and cardiovascular mortality. RESULTS: The study involved 338 patients with a median age of 67 (56-74) years, dialysis duration of 70 (33-141) months and diabetes prevalence of 39.1% (132/338). Patients with a CACS ≥400 (n = 222) had significantly higher age, dialysis duration, male prevalence, diabetes prevalence, C-reactive protein, predialysis ß2-MG, OH, extracellular water/total body water and overhydration/extracellular water (OH/ECW) but significantly lower Kt/Vurea than patients with a CACS <400 (n = 116) (p < .05). OH/ECW, Kt/Vurea and predialysis ß2-MG were significant predictors of a CACS ≥400 (p < .05) after adjusting for age, dialysis duration, serum phosphate and magnesium. In all patients, cut-off values of OH/ECW, Kt/Vurea and predialysis ß2-MG for a CACS ≥400 were 16%, 1.74 and 28 mg/L, respectively. After adjusting for dialysis duration, OH/ECW ≥16%, Kt/Vurea ≥1.74 and ß2-MG ≥28 mg/L were significant predictors of 3-year all-cause mortality but not 3-year cardiovascular mortality. CONCLUSION: Higher OH/ECW, higher predialysis ß2-MG and lower Kt/Vurea values are significant risk factors for a CACS ≥400 and 3-year all-cause mortality in patients undergoing maintenance HD.

Clinical implications of diverse calcification patterns in endovascular therapy for femoral-popliteal arterial occlusive disease.

OBJECTIVE: The aim of this study was to investigate whether intimal arterial calcification (IAC) and medial arterial calcification (MAC) are correlated with the various clinical outcomes following endovascular therapy (EVT) for peripheral arterial disease (PAD). METHODS: This single-center retrospective study comprised 154 consecutively hospitalized individuals with PAD who underwent EVT for de novo femoral-popliteal calcific lesions from January 2016 to July 2021. The predominant calcification patterns of IAC and MAC were assessed using a semi-quantitative computed tomography scoring system. The Kaplan-Meier method and Cox regression were conducted to evaluate the correlations between calcification patterns and medium- to long-term outcomes. RESULTS: The distribution of calcification patterns was as follows: IAC in 111 patients (72%) and MAC in 43 patients (28%). No remarkable variation was noted between the IAC and MAC groups regarding age (P = .84) and gender (P = .23). The MAC group indicated lower rates of 4-year primary patency, assisted primary patency, secondary patency, and amputation-free survival (AFS) compared with the IAC group (24% ± 7% vs 40% ± 6%; P = .003; 30% ± 8% vs 51% ± 6%; P = .001; 51% ± 8% vs 65% ± 5%; P = .004; and 43% ± 9% vs 76% ± 5%; P < .001, respectively). There was no significant difference in the rate of freedom from clinically driven target lesion revascularization between the MAC and IAC groups (63% ± 10% vs 73% ± 5%; P = .26). Stepwise multivariable Cox regression analysis demonstrated that MAC was associated with poor patency (hazard ratio, 1.81; 95% confidence interval, 1.12-2.93; P = .016) and AFS (hazard ratio, 2.80; 95% confidence interval, 1.52-5.16; P = .001). CONCLUSIONS: Compared with IAC, MAC is independently associated with lower medium- to long-term patency and AFS after EVT for de novo femoral-popliteal occlusive lesions.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

Coronary artery calcium and the risk of cardiovascular events and mortality in younger adults: a meta-analysis.

AIMS: American College of Cardiology/American Heart Association 2019 prevention guidelines recommend utilizing coronary artery calcium (CAC) to stratify cardiovascular risk in selected cases. However, data regarding CAC and risk in younger adults are less robust due to the lower prevalence of CAC and lower incidence of events. The objective of this meta-analysis is to determine the ability of CAC to predict the risk of cardiovascular events and mortality in adults <50. METHODS AND RESULTS: PubMed and Cochrane CENTRAL databases were electronically searched through May 2022 for studies with a primary prevention cohort under age 55 who underwent CAC scoring. Six observational studies with a total of 45 919 individuals with an average age of 43.1 and mean follow-up of 12.1 years were included. The presence of CAC was associated with an increased risk of adverse events [pooled hazard ratio (HR) = 1.80, 95% confidence interval (CI) 1.26-2.56, P = 0.012, I2 = 65.5]. Compared with a CAC of 0, a CAC of 1-100 did carry an increased risk of cardiovascular events (pooled HR = 1.85, 95% CI 1.08-3.16, P = 0.0248, I2 = 50.3), but not mortality (pooled HR = 1.20, 95% CI 0.85-1.69, P = 0.2917), while a CAC > 100 did carry an increased risk of cardiovascular events (pooled HR = 6.57, 95% CI 3.23-13.36, P < 0.0001, I2 = 72.6) and mortality (pooled HR = 2.91, 95% CI 2.23-3.80, P < 0.0001). CONCLUSION: In a meta-analysis of younger adults undergoing CAC scoring, a CAC of 1-100 was associated with a higher likelihood of cardiovascular events, while a CAC > 100 was associated with a higher likelihood of cardiovascular events and mortality.

This paper compiles prior studies into a meta-analysis to clarify the ability of coronary artery calcium (CAC) to predict cardiovascular risk and mortality risk in adults < 55 years. • A mildly elevated CAC (1­100) in adults < 55 likely has an increased cardiovascular risk but does not appear to have an increased mortality risk. • A moderately or highly elevated CAC (>100) in adults < 55 has a substantial increase in cardiovascular risk and mortality risk.

The Combined Prognostic Significance of Alkaline Phosphatase and Intracranial Arterial Calcifications in Hemodialysis Patients.

INTRODUCTION: The prevalence of intracranial arterial calcification (ICAC) in maintenance hemodialysis (MHD) patients is about 90%, and its severity is correlated with age, hemodialysis vintage, and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient for medial calcification because of inhibition by pyrophosphate. Alkaline phosphatase (ALP) promotes calcification by hydrolyzing extracellular pyrophosphate. Epigenetic mechanisms involving ALP inhibition by apabetalone were investigated as a potential target for preventing vascular calcifications (VCs). This study assessed the combined impact of VCs and elevated serum ALP on mortality among chronic HD patients. METHODS: VCs represented by ICAC were measured simultaneously with mineral bone disease parameters including serum ALP of MHD patients who underwent noncontrast brain computed tomography from 2015 to 2018 in our institution. RESULTS: This retrospective study included 150 MHD patients (mean age 71.3 ± 12.1 years, 60.1% male). Of the total cohort, 12 (7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95% CI: 1.7-12.7) among patients with brain calcifications and normal ALP (p = 0.003) and odds ratios for all-cause mortality of 6.1 (95% CI: 2.1-17.7) among patients with brain calcifications and elevated ALP (p= 0.001). CONCLUSION: We found an independent association between ICAC and the risk of death among MHD patients. The combined effect of ICAC and elevated ALP was associated with a higher odds ratio for all-cause mortality in MHD patients and may contribute to the risk stratification of these patients.

IL-6 Is Associated with Progression of Coronary Artery Calcification and Mortality in Incident Dialysis Patients.

INTRODUCTION: Inflammation is important in the pathogenesis of atherosclerosis. Elevated interleukin-6 (IL-6) is associated with cardiovascular events and also predicts mortality in individuals with CKD. Our goal was to determine the association between IL-6, FGF23, and high-sensitivity C-reactive protein (hsCRP) on coronary artery calcification (CAC) progression and mortality in incident dialysis patients without prior coronary events. METHODS: A prospective cohort of incident adult dialysis participants had CAC measured by ECG-triggered multislice CT scans at baseline and at least 12 months later. Lipids, mineral metabolism markers, FGF23, and inflammatory markers, such as IL-6 and hsCRP, were measured at the baseline visit. RESULTS: Participants in the high IL-6 tertile had the highest baseline CAC score (133.25 [10.35-466.15]) compared to the low (0.25 [0-212.2]) and intermediate (29.55 [0-182.85]) tertiles. Almost half of the participants with high IL-6 (15 of 32 [46.9%]) experienced progression of CAC compared to participants with low (8 of 32 [25%]) and intermediate (9 of 32 [28.1%]) (p = 0.05) IL-6 levels. Each log increase in IL-6 was associated with increase in death (hazard ratio 2.2, 95% CI: 1.2-3.8; p = 0.01). After adjusting for smoking, age, gender, race, diabetes, phosphate, and baseline calcium score, IL-6 (log) was associated with 2.2 times (95% CI: 1.1-4.6; p = 0.03) increase in death. CONCLUSION: IL-6 is associated with progression of CAC and mortality in incident dialysis patients.

Incremental Prognostic Value of Coronary Artery Calcium Score for Predicting All-Cause Mortality after Transcatheter Aortic Valve Replacement.

Background Current risk models show limited performances for predicting all-cause mortality after transcatheter aortic valve replacement (TAVR). Purpose To determine the prognostic value of coronary artery calcium (CAC) scoring for predicting 30-day and 1-year mortality in patients undergoing TAVR. Materials and Methods In this single-center institutional review board-approved secondary analysis of prospectively collected data (SwissTAVI Registry), the authors evaluated participants who, before TAVR, underwent CT that included a nonenhanced electrocardiography-gated cardiac scan between May 2008 and September 2019 and who had not undergone previous coronary revascularization. Clinical data, including the European System for Cardiac Operative Risk Evaluation (EuroSCORE II), were recorded. The CAC score was determined, and 30-day and 1-year all-cause mortality were assessed by using Cox regression analyses. Results In total, 309 participants (mean age ± standard deviation, 81 years ± 7; 175 women) were included, with a median CAC score of 334 (interquartile range, 104-987). Seventy-seven of the 309 participants (25%) had a CAC score greater than or equal to 1000. A CAC score of 1000 or greater served as an independent predictor of 30-day (hazard ratio [HR], 4.5 [95% CI: 1.5, 13.6] compared with a CAC score <1000; P = .007) and 1-year (HR, 4.3 [95% CI: 1.5, 12.7] compared with a CAC score of 0-99; P = .008) mortality after TAVR. Similar trends were observed for each point increase of the EuroSCORE II as an independent predictor of 30-day (HR, 1.22 [95% CI: 1.10, 1.36]; P < .001) and 1-year (HR, 1.16 [95% CI: 1.08, 1.25]; P < .001) mortality. Adding the CAC score to the EuroSCORE II provided incremental prognostic value for 1-year mortality after TAVR over the EuroSCORE II alone (concordance index, 0.76 vs 0.69; P = .04). Conclusion In participants without prior coronary revascularization, the coronary artery calcium score represented an independent predictor of 30-day and 1-year mortality after transcatheter aortic valve replacement. ClinicalTrials.gov identifier, NCT01368250 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Vascular Calcification Progression Modulates the Risk Associated with Vascular Calcification Burden in Incident to Dialysis Patients.

Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29; 95% confidence interval: 1.17-1.44) and CACP (HR: 5.16; 2.61-10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients.

C-factor: a summary measure for systemic arterial calcifications.

BACKGROUND: Arterial calcification, the hallmark of arteriosclerosis, has a widespread distribution in the human body with only moderate correlation among sites. Hitherto, a single measure capturing the systemic burden of arterial calcification was lacking. In this paper, we propose the C-factor as an overall measure of calcification burden. METHODS: To quantify calcification in the coronary arteries, aortic arch, extra- and intracranial carotid arteries, and vertebrobasilar arteries, 2384 Rotterdam Study participants underwent cardiac and extra-cardiac non-enhanced CT. We performed principal component analyses on the calcification volumes of all twenty-six possible combinations of these vessel beds. Each analysis' first principal component represents the C-factor. Subsequently, we determined the correlation between the C-factor derived from all vessel beds and the other C-factors with intraclass correlation coefficient (ICC) analyses. Finally, we examined the association of the C-factor and calcification in the separate vessel beds with cardiovascular, non-cardiovascular, and overall mortality using Cox-regression analyses. RESULTS: The ICCs ranged from 0.80 to 0.99. Larger calcification volumes and a higher C-factor were all individually associated with higher risk of cardiovascular, non-cardiovascular, and overall mortality. When included simultaneously in a model, the C-factor was still associated with all three mortality types (adjusted hazard ratio per standard deviation increase (HR) > 1.52), whereas associations of the separate vessel beds with mortality attenuated substantially (HR < 1.26). CONCLUSIONS: The C-factor summarizes the systemic component of arterial calcification on an individual level and appears robust among different combinations of vessel beds. Importantly, when mutually adjusted, the C-factor retains its strength of association with mortality while the site-specific associations attenuate.

Impact of Coronary Calcification on Clinical Outcomes After Implantation of Newer-Generation Drug-Eluting Stents.

Background Percutaneous coronary intervention of calcified lesions was associated with worse outcomes in the era of bare-metal and first-generation drug-eluting stents. Data on percutaneous coronary intervention of calcified lesions with newer-generation drug-eluting stents are scarce. Therefore, we investigated the impact of lesion calcification on clinical outcomes in patients undergoing percutaneous coronary intervention with a bioresorbable-polymer sirolimus-eluting stent or a durable-polymer everolimus-eluting stent. Methods and Results Patients (n=2361) from BIOFLOW II, IV, and V trials were categorized into moderate/severe versus none/mild lesion calcification by a core laboratory. End points were target-lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or target-lesion revascularization) and probable/definite stent thrombosis at 2 years. The agreement in calcification assessment between the operator and the core laboratory was weak (weighted κ, 0.23). Patients with moderate/severe calcification (n=303; 16%) had higher TLF (13.5% versus 8.4%; P=0.003) and stent thrombosis rates (2.1% versus 0.2%; P<0.0001), whereas target-lesion revascularization was not different between the groups (5.0% versus 3.9%; P=0.302). After adjustment, calcification did not emerge as an independent predictor of TLF (adjusted hazard ratio [aHR], 1.37; 95% CI, 0.89-2.08; P=0.148) but did for target-vessel myocardial infarction (aHR, 1.66; 95% CI, 1.03-2.68; P=0.037). TLF rates were similar between bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent (12.6% versus 15.4%, P=0.482) in moderate/severe calcification. In none/mild calcification, the bioresorbable-polymer sirolimus-eluting stent showed lower TLF (7.5% versus 10.3%, P=0.045). Conclusions With newer-generation drug-eluting stents, moderate/severe lesion calcification was not associated with more TLF after adjustment for the higher risk of patients with coronary calcification, whereas the rate of target-vessel myocardial infarction was higher. The bioresorbable-polymer sirolimus-eluting stent and durable-polymer everolimus-eluting stent were equally effective and safe in calcified lesions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01356888, NCT01939249, NCT02389946.