A national cross-sectional analysis of dietary copper intake and abdominal aortic calcification in the US adults: NHANES 2013-2014.

BACKGROUND AND AIMS: Copper is an essential dietary element with a crucial role in physiological regulation. However, the relationship between dietary copper intake and abdominal aortic calcification (AAC) remains uncertain. METHODS AND RESULTS: This study encompassed a cohort of 2535 adults aged over 40 years, derived from the National Health and Nutrition Examination Survey 2013-2014. Dietary copper intake from both food sources and supplements was assessed through two 24-h dietary recall interviews. AAC was measured by dual-energy X-ray absorptiometry and classified into 3 groups using the Kauppila score system. Multivariable logistic regression models were constructed to evaluate the association between dietary copper intake and AAC. Among the participants, a total of 771 individuals (30.4%) were diagnosed with AAC, of which 239 (9.4%) exhibited severe AAC. Higher dietary copper intake was significantly associated with a lower incidence of severe AAC. Specifically, for each 1 mg/day increase in dietary copper intake, the incidence of severe AAC decreased by 38% (odds ratios [OR] 0.62, 95% confidence intervals [CI] 0.39-0.98) after adjustment for relevant covariates. Moreover, individuals in the third tertile of copper intake had a 37% lower incidence of AAC compared to those in the first tertile [OR 0.63, 95% CI (0.43-0.95)]. However, no significant associations were found between supplemental copper intake or serum copper levels and AAC. CONCLUSIONS: This study demonstrates that lower dietary copper intake, rather than serum copper levels or supplement copper intake, is significantly associated with a higher prevalence of AAC in adults ≥40 years old in the United States.

Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease.

BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.

Atherogenic Indices as a Predictor of Aortic Calcification in Prostate Cancer Patients Assessed Using 18F-Sodium Fluoride PET/CT.

A major pathophysiological cause of cardiovascular disease is vascular plaque calcification. Fluorine 18−Sodium Fluoride (18F-NaF) PET/CT can be used as a sensitive imaging modality for detection of vascular calcification. The aim of this study was to find a non-invasive, cost-efficient, and readily available metric for predicting vascular calcification severity. This retrospective study was performed on 36 participants who underwent 18F-NaF fused PET/CT scans. The mean standard uptake values (SUVs) were calculated from manually sectioned axial sections over the aortic arch and thoracic aorta. Correlation analyses were performed between SUVs and calculated atherogenic indices (AIs). Castelli's Risk Index I (r = 0.63, p < 0.0001), Castelli's Risk Index II (r = 0.64, p < 0.0001), Atherogenic Coefficient (r = 0.63, p < 0.0001), Atherogenic Index of Plasma (r = 0.51, p = 0.00152), and standalone high-density lipoprotein (HDL) cholesterol (r = −0.53, p = 0.000786) were associated with aortic calcification. AIs show strong association with aortic arch and thoracic aorta calcifications. AIs are better predictors of vascular calcification compared to standalone lipid metrics, with the exception of HDL cholesterol. Clinical application of AIs provides a holistic metric beneficial for enhancing screening and treatment protocols.

Using a machine learning-based risk prediction model to analyze the coronary artery calcification score and predict coronary heart disease and risk assessment.

OBJECTIVES: To calculate the coronary artery calcification score (CACS) obtained from coronary artery computed tomography angiography (CCTA) examination and combine it with the influencing factors of coronary artery calcification (CAC), which is then analyzed by machine learning (ML) to predict the probability of coronary heart disease(CHD). METHODS: All patients who were admitted to the Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University from January 2019 to March 2022, suspected of CHD, and underwent CCTA inspection were retrospectively selected. The degree of CAC was quantified based on the Agatston score. To compare the correlation between the CACS and clinical-related factors, we collected 31 variables, including hypertension, diabetes, smoking, hyperlipidemia, among others. ML models containing the random forest (RF), radial basis function neural network (RBFNN),support vector machine (SVM),K-Nearest Neighbor algorithm (KNN) and kernel ridge regression (KRR) were used to assess the risk of CHD based on CACS and clinical-related factors. RESULTS: Among the five ML models, RF achieves the best performance about accuracy (ACC) (78.96%), sensitivity (SN) (93.86%), specificity(Spe) (51.13%), and Matthew's correlation coefficient (MCC) (0.5192).It also has the best area under the receiver operator characteristic curve (ROC) (0.8375), which is far superior to the other four ML models. CONCLUSION: Computer ML model analysis confirmed the importance of CACS in predicting the occurrence of CHD, especially the outstanding RF model, making it another advancement of the ML model in the field of medical analysis.

Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease.

BACKGROUND: Arterial stiffness and calcification propensity are associated with high cardiovascular risk and increased mortality in chronic kidney disease (CKD). Both magnesium and phosphate are recognized as modulators of vascular calcification and chronic inflammation, both features of CKD that contribute to arterial stiffness. In this paper, we outline the rationale and design of a randomized controlled trial (RCT) investigating whether 24 weeks of oral magnesium supplementation with or without additional phosphate-binding therapy can improve arterial stiffness and calcification propensity in patients with stage 3-4 CKD. METHODS: In this multi-center, placebo-controlled RCT, a total of 180 participants with an estimated glomerular filtration rate of 15 to 50 ml/min/1.73 m2 without phosphate binder therapy will be recruited. During the 24 weeks intervention, participants will be randomized to one of four intervention groups to receive either magnesium citrate (350 mg elemental magnesium/day) or placebo, with or without the addition of the phosphate binder sucroferric oxyhydroxide (1000 mg/day). Primary outcome of the study is the change of arterial stiffness measured by the carotid-femoral pulse wave velocity over 24 weeks. Secondary outcomes include markers of calcification and inflammation, among others calcification propensity (T50) and high-sensitivity C-reactive protein. As explorative endpoints, repeated 18F-FDG and 18F-NaF PET-scans will be performed in a subset of participants (n = 40). Measurements of primary and secondary endpoints are performed at baseline, 12 and 24 weeks. DISCUSSION: The combined intervention of magnesium citrate supplementation and phosphate-lowering therapy with sucroferric oxyhydroxide, in stage 3-4 CKD patients without overt hyperphosphatemia, aims to modulate the complex and deregulated mineral metabolism leading to vascular calcification and arterial stiffness and to establish to what extent this is mediated by T50 changes. The results of this combined intervention may contribute to future early interventions for CKD patients to reduce the risk of CVD and mortality. TRIAL REGISTRATION: Netherlands Trial Register, NL8252 (registered December 2019), EU clinical Trial Register 2019-001306-23 (registered November 2019).

"RotaTripsy": Combination of Rotational Atherectomy and Intravascular Lithotripsy in Heavily Calcified Coronary Lesions: A Case Series.

Heavily calcified coronary lesions increase the complexity of percutaneous coronary interventions (PCI) and represent a challenge for interventional cardiologists. They are an important cause of stent underexpansion and poor clinical outcome. Nowadays, there are different dedicated devices which enhance the chances of success. Rotational atherectomy is the first-line modality which permits to cross balloons or stents through severe calcified lesions. However, when circumferential deep calcium plaques exist may not be enough to achieve adequate expansion of these devices. In these cases, the complementary use of intracoronary lithotripsy ("RotaTripsy") can be an effective approach that further modifies the calcified plaque and enables optimal stent implantation. We present the first case series undergoing PCI using "RotaTripsy" technique.

Case 296: Phlebosclerotic Colitis.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range, <1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography. She underwent subsequent evaluation with noncontrast CT of the abdomen and colonoscopy.

Coronary CT Angiography CAD-RADS versus Coronary Artery Calcium Score in Patients with Acute Chest Pain.

Background The Coronary Artery Disease Reporting and Data System (CAD-RADS) was established in 2016 to standardize the reporting of coronary artery disease at coronary CT angiography (CCTA). Purpose To assess the prognostic value of CAD-RADS at CCTA for major adverse cardiovascular events (MACEs) in patients presenting to the emergency department with chest pain. Materials and Methods This multicenter retrospective observational cohort study was conducted at four qualifying university teaching hospitals. Patients presenting to the emergency department with acute chest pain underwent CCTA between January 2010 and December 2017. Multivariable Cox regression analysis was used to evaluate risk factors for MACEs, including clinical factors, coronary artery calcium score (CACS), and CAD-RADS categories. The prognostic value compared with clinical risk factors and CACS was also assessed. Results A total of 1492 patients were evaluated (mean age, 58 years ± 14 years [standard deviation]; 759 men). During a median follow-up period of 31.5 months, 103 of the 1492 patients (7%) experienced MACEs. Multivariable Cox regression analysis showed that a moderate to severe CACS was associated with MACEs after adjusting for clinical risk factors (hazard ratio [HR] range, 2.3-4.4; P value range, <.001 to <.01). CAD-RADS categories from 3 to 4 or 5 (HR range, 3.2-8.5; P < .001) and high-risk plaques (HR = 3.6, P < .001) were also associated with MACEs. The C statistics revealed that the CAD-RADS score improved risk stratification more than that using clinical risk factors alone or combined with CACS (C-index, 0.85 vs 0.63 [P < .001] and 0.76 [P < .01], respectively). Conclusion The Coronary Artery Disease Reporting and Data System classification had an incremental prognostic value compared with the coronary artery calcium score in the prediction of major adverse cardiovascular events in patients presenting to the emergency department with acute chest pain. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vliegenthart in this issue.

Idiopathic mesenteric phlebosclerosis associated with use of Chinese herbal medicine: Two case reports.

RATIONALE: Idiopathic mesenteric phlebosclerosis (IMP) is a rare form of ischemic colitis. It is more common in the Asian population people with Asian ancestry. Disease pathogenesis and etiology are not fully elucidated but may be associated with the long-term intake of toxins and other substances, including Chinese herbs. The disease has typical radiological and endoscopic features. Radiologic examination combined with endoscopy can lead to a conclusive diagnosis. PATIENT CONCERNS: We present 2 cases of IMP: in male patients aged 66 and 79 years. The first patient presented with diarrhea and abdominal pain, and the second patient presented with numbness of limbs and abdominal discomfort. These patients had a history of long-term use of Chinese herbal medicine (CHM). DIAGNOSIS: Both patients were diagnosed with IMP by endoscopy and radiology, and the diagnosis confirmed by biopsy in the first patient. INTERVENTIONS: The first patient was advised to stop using CHM. Both patients were given conservative treatment and were followed up regularly. OUTCOMES: Symptoms improved after conservative treatment. The patients had no obvious discomfort during the follow-up period. CONCLUSION: We suspect that the disease is induced by the long-term use of CHM, and dosage and duration of use may determine disease severity.

Association between waist-hip ratio and coronary artery calcification in postmenopausal women.

OBJECTIVE: Many studies have reported that body composition might be associated with cardiovascular disease, but the issue has not been fully investigated in postmenopausal women. METHODS: This retrospective study comprised 582 postmenopausal women without a history of cardiovascular disease who visited the Health Promotion Center between May 2008 and February 2018. All women were screened for body fat composition by bioelectrical impedance analysis and for degree of coronary artery calcification (CAC) by multidetector computed tomography. In addition, multivariate analysis, integrated discrimination improvement, and category-free net reclassification improvement were performed. RESULTS: The level of triglycerides, and the waist-hip ratio (WHR) in participants with CAC (coronary artery calcium score [CACS] > 0) were higher than in participants with a CACS of zero points. When the participants were stratified into four groups according to WHR, participants with CAC (CACS > 0) increased significantly as WHR quartile increased. A multivariate analysis showed that older age (odds ratio [OR]: 2.539; 95% confidence interval [CI]: 1.524-4.230; P < 0.001), triglyceride level (OR: 1.005; 95% CI: 1.002-1.008; P = 0.003), WHR (OR: 1.103; 95% CI: 1.018-1.195; P = 0.017), and history of hypertension (OR: 2.701; 95% CI: 1.715-4.253; P < 0.001) were significantly associated with CAC. The Brier score upon adding WHR to a clinical model was lower than that of the clinical model without WHR. Adding WHR to a clinical model better predicted CAC than a clinical model without WHR (C index: 0.761, 95% CI: 0.724-0.795, P < 0.001; net reclassification improvement: 0.195, P = 0.037; integrated discrimination improvement: 1.02%, P = 0.043). CONCLUSIONS: In asymptomatic postmenopausal women, WHR as measured by bioelectrical impedance analysis was significantly associated with coronary atherosclerosis, supplementing information of usual clinical markers. Hence, WHR might be appropriate as a marker for early atherosclerosis.

Vitamin K for kidney transplant organ recipients: investigating vessel stiffness (ViKTORIES): study rationale and protocol of a randomised controlled trial.

BACKGROUND: Renal transplant recipients (RTRs) exhibit increased vascular stiffness and calcification; these parameters are associated with increased cardiovascular risk. Activity of endogenous calcification inhibitors such as matrix gla protein (MGP) is dependent on vitamin K. RTRs commonly have subclinical vitamin K deficiency. The Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel Stiffness (ViKTORIES) study assesses whether vitamin K supplementation reduces vascular stiffness and calcification in a diverse population of RTR. METHODS AND ANALYSIS: ViKTORIES (ISRCTN22012044) is a single-centre, phase II, parallel-group, randomised, double-blind, placebo-controlled trial of the effect of vitamin K supplementation in 90 prevalent RTR. Participants are eligible if they have a functioning renal transplant for >1 year. Those on warfarin, with atrial fibrillation, estimated glomerular filtration rate <15 mL/min/1.73 m2 or contraindications to MRI are excluded. Treatment is with vitamin K (menadiol diphosphate) 5 mg three times per week for 1 year or matching placebo. All participants have primary and secondary endpoint measures at 0 and 12 months. The primary endpoint is ascending aortic distensibility on cardiac MR imaging. Secondary endpoints include vascular calcification (coronary artery calcium score by CT), cardiac structure and function on MR, carotid-femoral pulse wave velocity, serum uncarboxylated MGP, transplant function, proteinuria and quality of life. The study is powered to detect 1.0×10-3 mm Hg-1 improvement in ascending aortic distensibility in the vitamin K group relative to placebo at 12 months. Analyses will be conducted as between-group differences at 12 months by intention to treat. DISCUSSION: This trial may identify a novel, inexpensive and low-risk treatment to improve surrogate markers of cardiovascular risk in RTR.

X-ray Micro-Computed Tomography: An Emerging Technology to Analyze Vascular Calcification in Animal Models.

Vascular calcification describes the formation of mineralized tissue within the blood vessel wall, and it is highly associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease, diabetes, and atherosclerosis. In this article, we briefly review different rodent models used to study vascular calcification in vivo, and critically assess the strengths and weaknesses of the current techniques used to analyze and quantify calcification in these models, namely 2-D histology and the o-cresolphthalein assay. In light of this, we examine X-ray micro-computed tomography (µCT) as an emerging complementary tool for the analysis of vascular calcification in animal models. We demonstrate that this non-destructive technique allows us to simultaneously quantify and localize calcification in an intact vessel in 3-D, and we consider recent advances in µCT sample preparation techniques. This review also discusses the potential to combine 3-D µCT analyses with subsequent 2-D histological, immunohistochemical, and proteomic approaches in correlative microscopy workflows to obtain rich, multifaceted information on calcification volume, calcification load, and signaling mechanisms from within the same arterial segment. In conclusion we briefly discuss the potential use of µCT to visualize and measure vascular calcification in vivo in real-time.

Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature.

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.

Deep Learning for Automatic Calcium Scoring in CT: Validation Using Multiple Cardiac CT and Chest CT Protocols.

Background Although several deep learning (DL) calcium scoring methods have achieved excellent performance for specific CT protocols, their performance in a range of CT examination types is unknown. Purpose To evaluate the performance of a DL method for automatic calcium scoring across a wide range of CT examination types and to investigate whether the method can adapt to different types of CT examinations when representative images are added to the existing training data set. Materials and Methods The study included 7240 participants who underwent various types of nonenhanced CT examinations that included the heart: coronary artery calcium (CAC) scoring CT, diagnostic CT of the chest, PET attenuation correction CT, radiation therapy treatment planning CT, CAC screening CT, and low-dose CT of the chest. CAC and thoracic aorta calcification (TAC) were quantified using a convolutional neural network trained with (a) 1181 low-dose chest CT examinations (baseline), (b) a small set of examinations of the respective type supplemented to the baseline (data specific), and (c) a combination of examinations of all available types (combined). Supplemental training sets contained 199-568 CT images depending on the calcium burden of each population. The DL algorithm performance was evaluated with intraclass correlation coefficients (ICCs) between DL and manual (Agatston) CAC and (volume) TAC scoring and with linearly weighted κ values for cardiovascular risk categories (Agatston score; cardiovascular disease risk categories: 0, 1-10, 11-100, 101-400, >400). Results At baseline, the DL algorithm yielded ICCs of 0.79-0.97 for CAC and 0.66-0.98 for TAC across the range of different types of CT examinations. ICCs improved to 0.84-0.99 (CAC) and 0.92-0.99 (TAC) for CT protocol-specific training and to 0.85-0.99 (CAC) and 0.96-0.99 (TAC) for combined training. For assignment of cardiovascular disease risk category, the κ value for all test CT scans was 0.90 (95% confidence interval [CI]: 0.89, 0.91) for the baseline training. It increased to 0.92 (95% CI: 0.91, 0.93) for both data-specific and combined training. Conclusion A deep learning calcium scoring algorithm for quantification of coronary and thoracic calcium was robust, despite substantial differences in CT protocol and variations in subject population. Augmenting the algorithm training with CT protocol-specific images further improved algorithm performance. © RSNA, 2020 See also the editorial by Vannier in this issue.

Interior photon counting computed tomography for quantification of coronary artery calcium: pre-clinical phantom study.

Computed tomography (CT) is the reference method for cardiac imaging, but concerns have been raised regarding the radiation dose of CT examinations. Recently, photon counting detectors (PCDs) and interior tomography, in which the radiation beam is limited to the organ-of-interest, have been suggested for patient dose reduction. In this study, we investigated interior PCD-CT (iPCD-CT) for non-enhanced quantification of coronary artery calcium (CAC) using an anthropomorphic torso phantom and ex vivo coronary artery samples. We reconstructed the iPCD-CT measurements with filtered back projection (FBP), iterative total variation (TV) regularization, padded FBP, and adaptively detruncated FBP and adaptively detruncated TV. We compared the organ doses between conventional CT and iPCD-CT geometries, assessed the truncation and cupping artifacts with iPCD-CT, and evaluated the CAC quantification performance of iPCD-CT. With approximately the same effective dose between conventional CT geometry (0.30 mSv) and interior PCD-CT with 10.2 cm field-of-view (0.27 mSv), the organ dose of the heart was increased by 52.3% with interior PCD-CT when compared to CT. Conversely, the organ doses to peripheral and radiosensitive organs, such as the stomach (55.0% reduction), were often reduced with interior PCD-CT. FBP and TV did not sufficiently reduce the truncation artifact, whereas padded FBP and adaptively detruncated FBP and TV yielded satisfactory truncation artifact reduction. Notably, the adaptive detruncation algorithm reduced truncation artifacts effectively when it was combined with reconstruction detrending. With this approach, the CAC quantification accuracy was good, and the coronary artery disease grade reclassification rate was particularly low (5.6%). Thus, our results confirm that CAC quantification can be performed with the interior CT geometry, that the artifacts are effectively reduced with suitable interior reconstruction methods, and that interior tomography provides efficient patient dose reduction.

Idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy: A case report.

Idiopathic mesenteric phlebosclerosis is a rare entity characterized by chronic intestinal ischemia due to calcification and obstruction of the mesenteric veins. Here, we report a patient with idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy after evaluation by imaging studies. The patient was a 68-year-old Japanese woman with recurrent abdominal pain who had taken a Chinese herbal medicine for more than 20 years. Abdominal CT showed wall thickening of the right colon with calcification of branches of the superior mesenteric vein. Colonoscopy showed cyanotic mucosa from the cecum to the sigmoid colon. The affected area seen on colonoscopy extended to the distal colon. Despite discontinuation of the herbal medicine, her symptoms did not improve. Laparoscopic subtotal colectomy was performed. This report highlights the importance of appropriately evaluating the extent of the affected preoperatively area based on findings from colonoscopy, CT, and contrast enema.

Central cardiovascular calcifications: supplementation with Pycnogenol® and Centellicum®: variations over 12 months.

BACKGROUND: This 'concept' registry study evaluated the efficacy of Pycnogenol® and the combination Pycnogenol® and Centella Asiatica (Centellicum®) in controlling over 12 months the increasing number of arterial/cardiac calcifications in subjects with asymptomatic atherosclerosis. METHODS: The study included 3 groups of 30 males with asymptomatic coronary calcifications. Group one was followed with standard management (SM); group 2 used SM and Pycnogenol® (150 mg/day); group 3 used the combination Pycnogenol® (150 mg/day) + Centellicum® (450 mg/day). All subjects took cardioaspirin (Bayer, 100 mg/day). RESULTS: No dropouts, no clinical events were observed in 12 months. The 3 groups had comparable demographic and medical characteristics at baseline. No tolerability problems and no side effects from supplementation were reported. After 12 months, oxidative stress was significantly decreased (P<0.05) in both groups taking Pycnogenol®. The evaluation of the number of calcifications >1 mm indicated a trend in controls using SM towards a progressive increase in calcifications. At 12 months the decrease in the number of calcifications with the combined supplements (Pycnogenol® and Centellicum®) (group 3) was -9.952% and thus significantly better that in the other two groups (P<0.05). Pycnogenol® alone was more effective than SM alone in controlling the variation in calcifications (P<0.05). Considering a 34.88% increase in SM subjects, the total absolute difference between SM (34.8%) and the decrease observed in group 3 (-9.95%) was 44.75% (P<0.02). This indicates that supplementation with the combined supplements blocks the increase in calcified areas and, possibly, in time may decrease the number of calcified spots. CONCLUSIONS: This study shows that there is a significant activity of the complex Pycnogenol®+ Centellicum® in reducing the progressive diffusion of central cardiovascular calcifications-associated with advanced plaques - in a relatively short period of time. Longer studies - focusing also on events - may better evaluate the efficacy of these standardized supplements combination on the evolution of atherosclerosis.