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.

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.

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.

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.

The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

BACKGROUND: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE). METHODS: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE). RESULTS: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively). CONCLUSIONS: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.

Evaluating the Impact of Medial Arterial Calcification on Outcomes of Infrageniculate Endovascular Interventions for Treatment of Diabetic Foot Ulcers.

BACKGROUND: Medial arterial calcification (MAC) of the tibial and pedal arteries has been associated with an increased risk of amputation among people with diabetes. Endovascular interventions on infrageniculate vessels are frequently performed with the intent of treating peripheral artery disease (PAD) and decreasing the risk of amputation in those with diabetes. This study aimed to investigate how the extent of MAC impacts outcomes of endovascular procedures in people with diabetic foot ulcers (DFU). METHODS: We identified all patients who had undergone infrageniculate angioplasty in the setting of DFU at our institution between 2009 and 2019. Subjects were assigned a MAC score based on the severity of MAC in each vessel visualized on plain radiographs of the ankle and foot. We evaluated the relationship between MAC and the primary outcome, major adverse limb event (MALE), using stratified Cox proportional modeling. RESULTS: Among 99 subjects with DFU who had undergone infrageniculate angioplasty, MALE occurred in 50% (95% confidence interval [CI] 38%-61%) of patients within 1 year of intervention. On univariate Cox regression analysis, each 1 point increment in MAC score (hazard ratio [HR], 1.09; 95% CI 1.01-1.18), the third tertile of MAC score (HR, 2.27; 95% CI 1.01-5.11), age (HR 0.96; 95% CI 0.93-0.99), and wound grade (HR, 5.34; 95% CI 2.17-13.14), were significantly associated with increased risk of MALE. On adjusted analysis stratified by wound grade, MAC score was found to be associated with MALE only in patients with a low wound grade. CONCLUSION: Increased severity of MAC is associated with increased risk of MALE for subjects undergoing infrageniculate angioplasty with a low wound grade. Further research is needed to better understand the complex relationships of MAC, PAD, DFU, and interventions aimed at promoting healing of DFU.

Sex-Specific Outcome after Ascending Aortic Surgery in Moderate Hypothermic Circulatory Arrest.

BACKGROUND: Historically, female patients had worse outcome undergoing heart surgery. No recent data exist on gender-specific outcome after moderate hypothermic circulatory arrest (MHCA). The aim of this large retrospective analysis was to investigate gender disparity in patients undergoing elective surgery of ascending aorta in MHCA at 24°C. METHODS: We conducted a retrospective review of 905 (33.3% female) cases of elective heart surgery in MHCA for ascending aortic aneurysm (90.9%) or severely calcified aorta (12.5%) between 2001 and 2015. Furthermore, 299 female and 299 male patients matched by propensity score were compared. Patients with dissection of the aorta were excluded. RESULTS: Women were older (68.4 ± 9.9 vs. 65.8 ± 11.6 years; p = 0.002), had higher logistic EuroSCORE I (18.4 [11.7; 29.2] vs. 12.3% [7.4; 22.6]; p < 0.001), and significantly shorter cardiopulmonary bypass (CPB) time (132 [105; 175] vs. 150 [118; 192] minutes; p < 0.001), while mean MHCA time was longer (15 [13; 19] vs. 14 [12; 17] minutes; p = 0.003). Surgical procedures were less complex in women and they were treated more frequently by isolated supracoronary ascending aorta replacement (61 vs. 54%; p = 0.046). Postoperatively, men showed a higher incidence of neurologic complications (7.0 vs. 3.3%; p = 0.03). The 30-day mortality (women 4.9% vs. men 3.9%; p = 0.48) did not differ significantly, likewise after statistical matching (4.7 vs. 2.3%; p = 0.120). Age, CPB time, and blood transfusion, but not female gender, were risk factors for mortality in multivariable regression analysis. CONCLUSION: This study supports the hypothesis that female gender is not associated with increased short-term mortality or perioperative adverse events in elective aortic surgery in MHCA.

Vascular Calcifications are Associated with Increased Mortality in Patients with Acute Mesenteric Ischemia.

BACKGROUND: Vascular calcifications have been identified as predictors of mortality in several cardiovascular diseases but have not been investigated in context of acute mesenteric ischemia. The aim of this study was to investigate the impact of vascular calcifications in patients with acute mesenteric ischemia. METHODS: Patients admitted for an acute mesenteric ischemia were retrospectively included. The presence of calcifications in the visceral aorta, the celiac trunk, the superior mesenteric artery, and the renal arteries was assessed on computed tomography scan images at the arterial phase. The calcification volumes were measured using the software Aquarius iNtuition Edition®. RESULTS: The all-cause mortality was 55 out of 86 patients (63.9%) for a median follow-up of 3.5 days (1-243). The survival rate of patients with calcification in the superior mesenteric artery was significantly lower than that of those without calcification (22% vs. 55.6%, P = 0.019). Patients who died had significantly a higher frequency of calcifications in the superior mesenteric artery, the visceral aorta, the celiac trunk, and the renal arteries. CONCLUSIONS: The presence of vascular calcifications in the superior mesenteric artery is associated with increased mortality in patients diagnosed with acute mesenteric ischemia. Further studies are required to identify the mechanisms underlying this association.

Prognostic importance of coincidental coronary artery calcification on FDG-PET/CT oncology studies.

Coronary artery calcification (CAC) on body CT imaging is considered a coincidental finding in cancer patients. In order to determine the significance of CAC in cancer patients we evaluated the prognostic utility of CAC detected on oncology FDG-PET/CT studies. A retrospective study was performed of consecutive FDG-PET/CT studies from January to March 2011. CAC was identified on the CT portion of FDG/PET-CT studies. Chart review documented statin use, the Framingham risk score (FRS) (includes age, diabetes, hypertension, dyslipidemia and smoking), the primary malignancy and metastases. The primary end point was a composite of death and cardiovascular (CV) events (non-fatal myocardial infarction (MI), PCI or coronary artery bypass surgery (CABG)). 266 patients had a median follow up of 41 months (95% CI 31-56 months). CAC was noted in 140 patients. Based on CAC, potentially 84 patients would have had a change in statin prescribing (p < 0.01). CAC was associated with the primary end point on univariable and multivariable analysis (OR 2.6 (95% CI 1.42-4.77) (p < 0.01). On univariable Kaplan-Meier survival analysis, CAC was associated with decreased survival only in the absence of metastases (p < 0.01). Cox proportional hazard modelling demonstrated CAC was associated with mortality and cardiac events in patients without metastases, whereas FRS was not (For CAC: HR 1.69 (95% CI 1.22-2.35), p = 0.002). CAC is commonly detected with oncology FDG-PET/CT. In cancer patients CAC was associated with an increased risk of clinical events. CAC reduced survival free time in patients without metastases. CAC might therefore be considered more than a coincidentaloma in patients without metastases.

Rotational atherectomy with adjunctive balloon angioplasty in calcified chronic total occlusions of superficial femoral artery.

OBJECTIVES: The aim was to report the mid-term outcomes of Jetstream™ rotational atherectomy device in complex femoropopliteal lesions. METHODS: Between November 2016 and April 2018, 55 patients who were treated with rotational atherectomy and adjunctive balloon angioplasty due to complex femoropopliteal lesions were retrospectively scanned. RESULTS: Fifty-five patients who underwent endovascular treatment with rotational atherectomy for chronic total occlusive femoropopliteal lesions were included in the study. Technical success rate was 100%. The mean age was 63 (±10.5) years. The cohort included 25 (45.4%) diabetics and 45 (81.8%) current smokers. The mean length of the lesions was 20.8 ± 11.2 cm. Chronic total occlusive lesions were detected in 35 (63.6%) patients, and mixed-type steno-occlusive lesions were detected in 20 patients (36.4%). Thirty-three (60%) lesions were moderate or severely calcified. Adjunctive balloon angioplasty was performed with plain old balloon angioplasty (POBA) on 31 (56.4%) patients and with drug-coated balloon angioplasty on 24 (43.6%) patients. After adjunctive balloon angioplasty, flow limiting dissection was observed in 20 (36.3%) patients, and 17 (30.9%) patients needed stent implantation. The Kaplan-Meier analysis method estimated that the overall primary patency rates at 12 and 24 months were 81.8% and 70.9%, respectively. Overall, secondary patency rates at 12 and 24 months were 94.5% and 80%. No statistically significant differences of 24-month primary patency and secondary patency rates were found between patients treated with drug-coated balloon angioplasty and POBA as an adjunctive therapy, even though primary patency (83.3% vs. 61.3%, p = .06) and secondary patency (91.7% vs. 71%, p = .56) rates of drug-coated balloon angioplasty were slightly higher than POBA. Patients with claudication had better primary patency (90.5% vs. 58.8%, p = .001) and secondary patency (100% vs. 67.6%, p = .004) rates than patients with critical limb ischemia at 24 months. Significant differences between patients who did and did not stop smoking were found in 24-month primary patency (57% vs. 88%, p = .007) and secondary patency (67% vs. 96%, p = .007). Six patients underwent unplanned amputation. There were eight (14.5%) mortalities during follow-up. CONCLUSIONS: Rotational atherectomy with adjunctive balloon angioplasty has satisfactory technical success rates and mid-term outcomes. As an adjunctive method, there was no difference between drug-coated balloon angioplasty s and POBAs. Smoking cessation is always the first-step treatment to improve mid-term patency results. Patients with critical limb ischemia have worse patency results compared to the patients with claudication.

Coronary artery calcification scoring system based on the coronary artery calcium data and reporting system (CAC-DRS) predicts major adverse cardiovascular events or all-cause death in patients with potentially curable lung cancer without a history of cardiovascular disease.

The coronary artery calcium data and reporting system (CAC-DRS) is a novel reporting system based on CAC severity. Lung cancer patients have a high risk of cardiovascular disease (CVD), for which CAC severity may provide additional prognostic information. Using non-gated, non-contrast computed tomography (CT), we evaluated the CAC-DRS for predicting CVD and all-cause death in patients with potentially curable resected lung cancer. We retrospectively studied 309 consecutive patients without a history of CVD (mean age 67.4 ± 8.2 years, 61% male) who underwent curative surgery for non-small-cell lung cancer between May 2012 and March 2019 at the Japanese Red Cross Okayama Hospital. Time to incidence of major adverse cardiac events (MACEs) (non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and all-cause death was analyzed using Fine and Gray and Cox regression models. The CAC-DRS score was assessed using standard chest CT without electrocardiogram gating. During 52-months' median follow-up, 43 patients (13.4%) developed incident MACEs or died from any cause; the pathological cancer stages were Ia (n = 20), Ib (n = 8), IIa (n = 2), IIb (n = 2) and IIIa (n = 11). Patients had a graded increase in incidence of MACEs or all-cause death with increasing categories of CAC-DRS. The CAC-DRS score was significantly associated with incident MACEs or all-cause death after adjusting for confounding factors (hazard ratio 1.18; 95% confidence interval 1.10-1.25, p < 0.01). In conclusion, the CAC-DRS score on non-gated standard CT can predict incident MACEs and/or all-cause death in patients with potentially curable resected lung cancer. Lung cancer survivors with a greater CAC-DRS category may need more active management of cardiovascular risk factors.

Coronary Artery Calcium as a Synergistic Tool for the Age- and Sex-Specific Risk of Cardiovascular and Cancer Mortality: The Coronary Artery Calcium Consortium.

Background Coronary artery calcium (CAC) is a predictor for the development of cardiovascular disease (CVD) and to a lesser extent cancer. The age- and sex-specific relationship of CAC with CVD and cancer mortality is unknown. Methods and Results Asymptomatic patients aged 40 to 75 years old without known CVD were included from the CAC Consortium. We calculated sex-specific mortality rates per 1000 person-years' follow-up. Using parametric survival regression modeling, we determined the age- and sex-specific CAC score at which the risk of death from CVD and cancer were equal. Among the 59 502 patients included in this analysis, the mean age was 54.9 (±8.5) years, 34% were women, and 89% were white. There were 671 deaths attributable to CVD and 954 deaths attributable to cancer over a mean follow-up of 12±3 years. Among patients with CAC=0, cancer was the leading cause of death, the total mortality rate was low (women, 1.8; men, 1.5), and the CVD mortality rate was exceedingly low for women (0.3) and men (0.3). The age-specific CAC score at which the risk of CVD and cancer mortality were equal had a U-shaped relationship for women, while the relationship was exponential for men. Conclusions The age- and sex-specific relationship of CAC with CVD and cancer mortality differed significantly for women and men. Our age- and sex-specific CAC score provides a more precise estimate and further facilitates the use of CAC as a synergistic tool in strategies for the prediction and prevention of CVD and cancer mortality.

Low Iliofemoral Calcium Score May Predict Higher Survival after EVAR and FEVAR.

BACKGROUND: Abdominal aortic aneurysm is associated with an increased mortality, mostly cardiovascular events. Moreover, aortoiliac calcification is associated with increased mortality in patients with peripheral occlusive disease. The aim of this study is to assess the potential association between iliofemoral calcification, assessed by calcium score, in patients undergoing infrarenal (endovascular aneurysm repair [EVAR]) or fenestrated endovascular aortic repair (FEVAR) and long-term mortality, particularly caused by cardiac events. METHODS: All patients with preoperative noncontrast-enhanced computed tomographic scans who underwent infrarenal EVAR and FEVAR of nonruptured abdominal aortic aneurysm between 2004 and 2012 at a single tertiary center were screened for inclusion. Agatston calcium score was measured from the aortic bifurcation to common femoral arteries using a dedicated postprocessing software. The values are presented as median and interquartile range. RESULTS: About 404 (62.05%) of 651 patients who underwent EVAR and FEVAR had sufficient imaging quality to be included. There was no difference in survival between included and excluded patients (P = 0.33). Nine patients (2.2%) died within 30 days of the operation, whereas the remaining were followed up for 6.3 (4.7-8.4) years. The iliofemoral calcium score was 8348 (3830-14,179). Estimated overall survival at 5 years was 73 ± 2%. Patients within the lowest quartile of iliofemoral calcium score had significantly higher overall survival (5 years: 79 ± 4% vs. 71 ± 3%; P = 0.01) and cardiac event-free survival (5 years: 95 ± 2% vs. 91 ± 2%; P = 0.033) when compared with the remaining ones. Calcium score was associated with neither univariate regression analysis with survival (odds ratio, 1.016 [0.988-1.045]; P = 0.268) nor cardiac event-free survival (odds ratio, 1.024 [0.986-1.063]; P = 0.222). CONCLUSIONS: Low iliofemoral calcium score may be associated with lower incidence of fatal cardiac events and all-cause long-term mortality after EVAR and FEVAR. This may be partially a reflection of aging and cardiovascular comorbidity but needs to be studied further.

The association of coronary artery calcium score and mortality risk among smokers: The coronary artery calcium consortium.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) and cancer are the two leading causes of death in smokers. Lung cancer screening is recommended in a large proportion of smokers. We examined the implication of coronary artery calcium (CAC) score (quantitative and qualitative) for cardiovascular disease (CVD), coronary heart disease (CHD), and cancer mortality risk prediction among current smokers. METHODS: We included current smokers without known heart disease from the CAC Consortium. Cox regression (for all-cause mortality) and Fine-and-Gray competing-risk regression (for CVD, CHD, and cancer mortality) models, adjusted for traditional CVD risk factors, were used to assess the association between CAC and each mortality outcome, with CAC as a continuous (log2-transformed) or categorical variable (CAC = 0, CAC = 1-99, CAC = 100-399, and CAC ≥400). We used number of vessels with CAC as a surrogate for the qualitative measure of CAC and mortality outcomes. Analyses were repeated for lung cancer screening-eligible population (defined as ever smokers with >30 pack years smoking history) (n = 1,149). Hazard ratios (HR) for all-cause mortality and Subdistribution HRs (sHR) with 95% confidence intervals (CI) were reported. RESULTS: Over a median of 11.9 years (25th-75th percentile: 10.2-13.3) of follow-up, of 5,147 current smokers (mean age 52.5 ± 9.4, 32.4% women) 337 died (102 of CVD, 54 of CHD, and 123 of cancer). A doubling of CAC score was associated with increased HRs of all-cause mortality (1.10 (1.06-1.14)), and sHRs for CVD (1.15 (1.07-1.24)), CHD (1.26 (1.11-1.42)) and cancer mortality (1.06 (1.00-1.13)). Those with CAC ≥400 had increased sHR of CVD (3.55 (1.70-7.41)), CHD (8.80 (2.41-32.10)), and cancer mortality (1.85 (1.07-3.22)), compared with those with CAC = 0. A diffuse CAC pattern significantly increased the risk of all-cause, CVD, and CHD mortality among smokers. Results were consistent for the lung cancer screening-eligible population. CONCLUSIONS: Qualitative and quantitative CAC scores can prognosticate risk of all-cause, CVD, CHD, and cancer mortality beyond traditional risk factors among all smokers as well as those eligible for lung cancer screening.

All-cause and cause-specific mortality in individuals with zero and minimal coronary artery calcium: A long-term, competing risk analysis in the Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: The long-term associations between zero, minimal coronary artery calcium (CAC) and cause-specific mortality are currently unknown, particularly after accounting for competing risks with other causes of death. METHODS: We evaluated 66,363 individuals from the CAC Consortium (mean age 54 years, 33% women), a multi-center, retrospective cohort study of asymptomatic individuals undergoing CAC scoring for clinical risk assessment. Baseline evaluations occurred between 1991 and 2010. RESULTS: Over a mean of 12 years of follow-up, individuals with CAC = 0 (45% prevalence, mean age 45 years) had stable low rates of coronary heart disease (CHD) death, cardiovascular disease (CVD) death (ranging 0.32 to 0.43 per 1000 person-years), and all-cause death (1.38-1.62 per 1000 person-years). Cancer was the predominant cause of death in this group, yet rates were also very low (0.47-0.79 per 1000 person-years). Compared to CAC = 0, individuals with CAC 1-10 had an increased multivariable-adjusted risk of CVD death only under age 40. Individuals with CAC>10 had multivariable-adjusted increased risks of CHD death, CVD death and all-cause death at all ages, and a higher proportion of CVD deaths. CONCLUSIONS: CAC = 0 is a frequent finding among individuals undergoing CAC scanning for risk assessment and is associated with low rates of all-cause death at 12 years of follow-up. Our results support the emerging consensus that CAC = 0 represents a unique population with favorable all-cause prognosis who may be considered for more flexible treatment goals in primary prevention. Detection of any CAC in young adults could be used to trigger aggressive preventive interventions.

The Impact of Femoropopliteal Artery Calcium Score after Endovascular Treatment.

BACKGROUND: The coronary artery calcium score is a widely known independent predictor of cardiac events. Tibial artery calcification had been reported as an amputation risk, but the femoropopliteal artery calcium score is rarely known. METHODS: A retrospective analysis was performed using the data collected from the patients who underwent endovascular treatment for the femoropopliteal artery between January 2010 and December 2017. The femoropopliteal artery calcium scores on preprocedural computed tomography were calculated according to the Agatston definition. The mean value of total of femoropopliteal artery calcium scores was used to divide the scores into two groups. The prognostic value of the calcium score was analyzed based on primary patency, clinically driven target lesion revascularization, major amputation, and all-cause death. RESULTS: In total, 132 consecutive limbs that underwent successful endovascular intervention were analyzed in this study; 44 and 88 limbs were assigned to the high and low calcium score groups, respectively. There were no significant differences between the two groups in terms of patient and lesion characteristics, except for chronic kidney disease (7% vs. 25%, P < 0.01), hemodialysis (80% vs. 25%, P < 0.01), and coronary artery disease (73% vs. 53%, P = 0.03). Compared with the low calcium score group, the high calcium score group had a significantly higher rate of loss of primary patency and clinically driven target lesion revascularization at one year, based on the Kaplan-Meier curve (55% vs. 81%, 44% vs. 8%, both P < 0.01). There were no significant differences between the two groups in terms of major amputation and death. Multivariate analysis revealed that hemodialysis [hazard ratio (HR): 1.9; 95% confidence interval (CI): 1.01-5.28; P = 0.04] runoff grade 0 (HR: 2.9; 95% CI: 1.02-10.9; P = 0.04), lesion length > 200 mm (HR: 3.9; 95% CI: 1.1-13.7; P = 0.03), and calcium score per 100 increase (HR: 1.05; 95% CI: 1.02-1.08; P < 0.01) were predictors of clinically driven target lesion revascularization. As per receiver operating characteristic analysis, the best cutoff value of target lesion calcium score for target lesion revascularization was 206. CONCLUSIONS: A high femoropopliteal artery calcium score might increase loss of patency and the risk for clinically driven target lesion revascularization.

Long-Term All-Cause and Cause-Specific Mortality in Asymptomatic Patients With CAC ≥1,000: Results From the CAC Consortium.

OBJECTIVES: This study thoroughly explored the demographic and imaging characteristics, as well as the all-cause and cause-specific mortality risks of patients with a coronary artery calcium (CAC) score ≥1,000 in the largest dataset of this population to date. BACKGROUND: CAC is commonly used to quantify cardiovascular risk. Current guidelines classify a CAC score of >300 or 400 as the highest risk group, yet little is known about the potentially unique imaging characteristics and mortality risk in individuals with a CAC score ≥1,000. METHODS: A total of 66,636 asymptomatic adults were included from the CAC consortium, a large retrospective multicenter clinical cohort. Mean patient follow-up was 12.3 ± 3.9 years for patients with cardiovascular disease (CVD), coronary heart disease (CHD), cancer, and all-cause mortality. Multivariate Cox proportional hazards regression models adjusted for age, sex, and conventional risk factors were used to assess the relative mortality hazard of individuals with CAC ≥1,000 compared with, first, a CAC reference of 0, and second, with patients with a CAC score of 400 to 999. RESULTS: There were 2,869 patients with CAC ≥1,000 (86.3% male, mean 66.3 ± 9.7 years of age). Most patients with CAC ≥1,000 had 4-vessel CAC (mean: 3.5 ± 0.6 vessels) and had greater total CAC area, higher mean CAC density, and more extracoronary calcium (79% with thoracic artery calcium, 46% with aortic valve calcium, and 21% with mitral valve calcium) than those with CAC scores of 400 to 999. After full adjustment, those with CAC ≥1,000 had a 5.04- (95% confidence interval [CI]: 3.92 to 6.48), 6.79- (95% CI: 4.74 to 9.73), 1.55- (95% CI:1.23 to 1.95), and 2.89-fold (95% CI: 2.53 to 3.31) risk of CVD, CHD, cancer, and all-cause mortality, respectively, compared to those with CAC score of 0. The CAC ≥1,000 group had a 1.71- (95% CI: 1.41 to 2.08), 1.84- (95% CI: 1.43 to 2.36), 1.36- (95% CI:1.07 to 1.73), and 1.51-fold (95% CI: 1.33 to 1.70) increased risk of CVD, CHD, cancer, and all-cause mortality compared to those with CAC scores 400 to 999. Graphic analysis of CAC ≥1,000 patients revealed continued logarithmic increase in risk, with no clear evidence of a risk plateau. CONCLUSIONS: Patients with extensive CAC (CAC ≥1,000) represent a unique very high-risk phenotype with mortality outcomes commensurate with high-risk secondary prevention patients. Future guidelines should consider CAC ≥1,000 patients to be a distinct risk group who may benefit from the most aggressive preventive therapy.