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This case report illustrates the clinical course and management strategy of severe catheter-induced vasospasm of the right coronary artery (RCA) resulting in brief cardiac arrest in a male patient in his 60s presenting with Non-ST elevation myocardial infarction and obstructive disease in the left anterior descending artery (LAD). The patient was successfully resuscitated and further stay was uneventful. Optical coherence tomography imaging following administration of intracoronary isosorbide dinitrate confirmed normal coronary anatomy and flow restoration in the RCA, suggesting that the index episode was probably a vasospasm of the RCA. After establishing coronary flow in the RCA, the stenosis in the LAD was treated with a drug-eluting stent. Invasive cardiologists should be aware of the catheter-induced coronary artery spasm, which may have important clinical implications particularly in the presence of concomitant atherosclerotic disease in other coronary arteries (in our case the LAD). This approach helps to avoid unnecessary coronary stenting.

Mechanical assist devices in refractory cardiac arrest are increasingly employed. We compared the hemodynamics and organ perfusion during cardiac arrest with either veno-arterial extracorporeal membrane oxygenation (ECMO) or biventricular assisted circulation combining left- and right-sided impeller devices (BiPella) in an acute experimental setting. Twenty pigs were randomized in two equal groups receiving circulatory support either by ECMO or by BiPella during 40 minutes of ventricular fibrillation (VF) followed by three attempts of cardioversion, and if successful, 60 minute observation with spontaneous, unsupported circulation. Hemodynamic variables were continuously recorded. Tissue perfusion was evaluated by fluorescent microsphere injections. Cardiac function was visualized by intracardiac echocardiography. During VF device output, carotid flow, kidney perfusion, mean aortic pressure (AOPmean), and mean left ventricular pressure (LVPmean) were all significantly higher in the ECMO group, and serum-lactate values were lower compared with the BiPella group. No difference in myocardial or cerebral perfusion was observed between groups. In 15 animals with sustained cardiac function for 60 minutes after return of spontaneous circulation, left ventricular subendocardial blood flow rate averaged 0.59 ± 0.05 ml/min/gm during VF compared with 0.31 ± 0.07 ml/min/gm in five animals with circulatory collapse (p = 0.005). Corresponding values for the midmyocardium was 0.91 ± 0.06 vs. 0.65 ± 0.15 ml/min/gm (p = 0.085). Both BiPella and ECMO could sustain vital organ function. ECMO provided a more optimal systemic circulatory support related to near physiologic output. Myocardial tissue perfusion and sustained cardiac function were related to coronary perfusion pressure during VF, irrespective of mode of circulatory support.

Aims To assess characteristics and outcome of patients treated with Impella for acute myocardial infarction (AMI) complicated by severe cardiogenic shock (CS) or cardiac arrest (CA). Methods and results From 2008 through 2017, 92 patients with AMI complicated by CS were treated with Impella. Survival varied according to clinical presentation. Patients in cardiogenic shock without CA had a 75% 30-day survival. Patients with CA and return of spontaneous circulation (ROSC) had a 43% survival and those with CA and ongoing cardio-pulmonary resuscitation (CPR) had a 6% 30-day survival. Age, pre-existing hypertension, coronary disease, ventilatory support and use of adrenergic agents were associated with worse prognosis. Complications were predominantly access site related. Conclusions In this registry of patients with AMICS treated with Impella, hypertension and older age were found to be negatively predictive for survival. Patients without CA had the highest 30-day survival. In patients with ROSC, survival was strongly related to age and comorbidity. Patients with ongoing CPR had very high mortality.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

Intravascular lithotripsy (IVL) has been shown to be safe and effective for calcium modification in nonocclusive coronary artery disease (CAD), but there are only case reports of its use in calcified chronic total occlusions (CTO). We report data from an international multicenter registry of IVL use during CTO percutaneous coronary intervention (PCI) and provide provisional data regarding its efficacy and safety. During the study period, IVL was used in 55 of 1053 (5.2%) CTO PCI procedures. IVL was used within the occluded segment after successful CTO crossing in 53 procedures and during incomplete CTO crossing in 2 cases. The mean J-CTO score was 3.1. CTO PCI technical and procedural success was achieved in 53 (96%) and 51 (93%) cases. Six patients had a procedural complication, with 3 main vessel perforations (5%). Two had covered stent implantation, one required pericardiocentesis, and one was managed conservatively. All had combination therapy with another calcium modification device. Two patients had a procedural myocardial infarction (PMI) (4%), and two others had a major adverse cardiovascular event (MACE) (4%) at a median follow-up of 13 (4–21) months. IVL can effectively facilitate calcium modification during CTO PCI. More data are required to establish the efficacy and safety of IVL and other calcium modification devices when used extraplaque or in combination during CTO PCI.

Introduction If reperfusion can be performed within 120 minutes, pPCI is the ESC guideline recommended treatment in patients with ST-elevation myocardial infarction (STEMI). Aims Historically, prognosis is dependent on time from diagnosis to reperfusion in patients with STEMI. We sought to investigate this in a contemporary patient population by assessing mortality as function of time from ECG diagnosis to sheath insertion in the Norwegian registry for invasive cardiology (NORIC). Methods NORIC, which is a part of the Norwegian Cardiovascular Disease Registry, is a national, mandatory and non-consensual person-identifiable health registry. Data from NORIC were linked with the National Population Register. Data were registered from 1st of January 2013 to 31st of June 2019. Results During this period complete data were available for n=5754 patients with 526 events. ECG diagnosis to sheath insertion was a predictor of mortality with the 4th (>106 min) vs 1st quartile ( Nationally 62% percent of the patients received pPCI within the ESC recommended 90 minutes from ECG-diagnosis with large geographical variation (range 38–89%). Nationally 80% received pPCI within 115 minutes (range 75–202 minutes). Conclusion In a contemporary STEMI population, time from ECG diagnosis to sheath insertion is a strong predictor for mortality in patients admitted for pPCI for STEMI. However, the data also demonstrate large variations between different geographical health regions in Norway that should be addressed. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Haukeland University Hospital

Background Plasma trimethylamine-N-oxide (TMAO) is associated with cardiovascular disease; however specific relationships with cardiac arrhythmias are unknown. We evaluated the association between plasma TMAO and incident atrial fibrillation (AF). Methods Risk associations were explored among 3797 patients with suspected stable angina in the Western Norway Coronary Angiography Cohort (WECAC) and verified in 3143 elderly participants in the community-based Hordaland Health Study (HUSK). Information on endpoints was obtained from nationwide registries. Results Median follow-up was 7.3 and 10.8 years in the WECAC and HUSK cohorts, respectively, and 412 (10.9%) and 484 (15.4%) subjects were registered with incident AF. The age and gender adjusted HRs were 1.16, 95% CI 1.05–1.28 and 1.10, 95% CI 1.004–1.19 per 1 SD increase in log-transformed plasma TMAO. Adjusting for hypertension, BMI, smoking, diabetes, or intake of total choline, a TMAO precursor, did not materially influence the risk associations. Among patients in WECAC, further extensive adjustment for other AF risk factors yielded similar results. Adding TMAO to traditional AF risk factors (age, gender, hypertension, BMI, smoking and diabetes) yielded a continuous net reclassification improvement of 0.108, 95% CI 0.015–0.202 and 0.139, 95% CI 0.042–0.235. Conclusions Plasma TMAO was associated with and improved reclassification of incident AF in two independent Norwegian cohorts with long-term follow-up. The relationship was independent of traditional AF risk factors, as well as of dietary choline intake. Our findings motivate further studies to explore endogenous metabolic factors influencing the relationship between TMAO and cardiovascular disease.

Context Carnitine and its metabolites are centrally involved in fatty acid metabolism. Although elevated circulating concentrations have been observed in obesity and insulin resistance, prospective studies examining whether these metabolites are associated with incident type 2 diabetes mellitus (T2D) are sparse. Objective We performed a comprehensive evaluation of metabolites along the carnitine pathway relative to incident T2D. Design A total of 2519 patients (73.1% men) with coronary artery disease, but without T2D, were followed for median 7.7 years until the end of 2009, during which 173 (6.9%) new cases of T2D were identified. Serum levels of free carnitine, its precursors trimethyllysine (TML) and γ-butyrobetaine, and the esters acetyl-, propionyl-, (iso)valeryl-, octanoyl-, and palmitoylcarnitine were measured by liquid chromatography/tandem mass spectrometry. Risk associations were explored by logistic regression and reported per (log-transformed) standard deviation increment. Results Median age at inclusion was 62 years and median body mass index (BMI) 26.0 kg/m2. In models adjusted for age, sex, fasting status, BMI, estimated glomerular filtration rate, glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, and study center, serum levels of TML and palmitoylcarnitine associated positively [odds ratio (95% confidence interval), 1.22 (1.04 to 1.43) and 1.24 (1.04 to 1.49), respectively], whereas γ-butyrobetaine associated negatively [odds ratio (95% confidence interval) 0.81 (0.66 to 0.98)] with T2D risk. Conclusion Serum levels of TML, γ-butyrobetaine, and the long-chained palmitoylcarnitine predict long-term risk of T2D independently of traditional risk factors, possibly reflecting dysfunctional fatty acid metabolism in patients susceptible to T2D development.

IntroductionTranscatheter aortic valve implantation (TAVI) is a widely used treatment option as an alternative to surgical aortic valve replacement in patients with severe aortic stenosis (AS) at high or intermediate surgical risk. TAVI improves symptoms, induces reverse left ventricular (LV) remodelling and increases overall survival. However, a careful patient selection is essential to achieve better outcome. Evidence on LV functional recovery and LV mass regression after TAVI based on contemporary registry data is scarce. The impact of TAVI on the arterial vasculature is also less explored.Method and analysesThis is a study of 600 consecutive patients with AS who underwent a TAVI at Haukeland University Hospital, Bergen, Norway. Demographics, clinical data, arterial haemodynamics and echocardiographic parameters were prospectively collected. In the present paper, we describe the design, major scientific objectives and echocardiography imaging protocol of the TAVI-NOR (TAVI in western NORway) study. The main objectives are: To explore the impact of TAVI on cardiac structure and function in patients with severe AS, identify the echocardiographic predictors of reverse LV remodelling, assess survival benefits according to baseline risk profile, evaluate long-term therapeutic success as reflected by reduction in valvular-arterial impedance and to investigate the impact of various types of blood pressure response immediately after TAVI on clinical outcome.Ethics and disseminationThe study was approved by the Regional Committees for Medical and Health Research Ethics (REK vest, ref. number 33814) and the Institutional Data Protection Services. Patients’ consent was waived. The study findings will be disseminated via peer-reviewed publications and presentation in national and international scientific meetings and conferences.Trail registration numberThe study was registered in the international database: ClinicalTrials.gov, Identifier: NCT04417829.

Background— Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)–mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common polymorphism in MTHFD1 have been associated with risk of acute myocardial infarction (AMI). It is, therefore, of interest to explore if these 2 pathways interact in relation to AMI. Methods and Results— A total of 2571 participants in the WENBIT (Western Norway B Vitamin Intervention Trial) undergoing coronary angiography for stable angina pectoris were studied. Associations of plasma serine and glycine concentrations with risk of AMI across 2 common and functional MTHFD1 polymorphisms ( rs2236225 and rs1076991 ) were explored in Cox regression models. During a median follow-up of 4.7 years, 212 patients (8.2%) experienced an AMI. In age- and sex-adjusted analyses, plasma glycine ( P P =0.52), showed an overall association with AMI. However, interactions of MTHFD1 rs2236225 polymorphism with both plasma serine and glycine were observed ( P interaction =0.03 for both). Low plasma serine and glycine were associated with an increased risk of AMI among patients carrying the rs2236225 minor A allele. Similarly, low plasma glycine showed stronger risk relationship with AMI in the rs1076991 CC genotype carriers but weaker associations in patients carrying the minor T allele ( P interaction =0.02). Conclusions— Our results showed that 2 common and functional polymorphisms in the MTHFD1 gene modulate the risk associations of plasma serine and glycine with AMI. These findings emphasize the possible role of the MTHFD1 in regulating serine and glycine metabolism in relation to atherosclerotic complications. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique Identifier: NCT00354081.

Objective: Associations of glycated hemoglobin A1c (HbA1c) levels to incident coronary and cardiovascular events among non-diabetic patients with coronary artery disease are unclear. We investigated relations of HbA1c to long-term prognosis in such patients. Methods: A prospective cohort of 2519 patients undergoing elective coronary angiography for suspected stable angina pectoris (SAP) was divided into pre-defined categories according to HbA1c (%) levels (

Low vitamin D status is associated with increased risk of cardiovascular disease and may be involved in atherosclerosis. Our aim was to assess the association between vitamin D status and the progression of coronary artery disease (CAD).We measured 25-hydroxyvitamin D3 (25OHD3) by liquid chromatography tandem mass spectrometry (LC-MS/MS) in plasma from 348 participants with established CAD (84% males, mean ± standard deviation (SD) age 60 ± 10 years) of the Western Norway B-vitamin Intervention Trial (WENBIT, 1999-2006). The patients underwent invasive coronary angiography (CA) and percutaneous coronary intervention at baseline and a second CA after 302 ± 79 days of follow-up. From the angiograms, minimal lumen diameter (MLD) and diameter stenosis (DS) of atherosclerotic lesions were obtained. Significant CAD in non-intervened vessels was found in 309 coronary arteries from 183 participants either at baseline and/or at follow-up. To assess the association between levels of 25OHD3 and CAD progression in non-intervened vessels, we applied a linear quantile fitted mixed effects model with MLD or DS measured at follow-up as a function of continuous 25OHD3 concentrations. There were no statistically significant associations between plasma 25OHD3 concentrations (median: 63.9, 95% confidence interval (CI): 48.1-78.5 nmol/l) measured at baseline and the follow-up measures of either MLD (estimated effect per 10 nmol/l increase of 25OHD3 and 95% CI: -0.015 (-0.032-0.002) mm, p = 0.088) or DS (0.225 (-0.354-0.804) percentage points, p = 0.444). Multivariate adjustment did not alter these results.Plasma 25OHD3 levels were not associated with 'one-year' progression of CAD, assessed by CA in statin-treated patients.

Objective— Dimethylglycine is linked to lipid metabolism, and increased plasma levels may be associated with adverse prognosis in patients with coronary artery disease. We evaluated the relationship between plasma dimethylglycine and risk of incident acute myocardial infarction in a large prospective cohort of patients with stable angina pectoris, of whom approximately two thirds were participants in a B-vitamin intervention trial. Model discrimination and reclassification when adding plasma dimethylglycine to established risk factors were obtained. We also explored temporal changes and the test–retest reliability of plasma dimethylglycine. Approach and Results— Four thousand one hundred fifty patients (72% men; median age 62 years) were included. Plasma dimethylglycine was associated with several traditional coronary artery disease risk factors. During a median follow-up of 4.6 years, 343 (8.3%) patients experienced an acute myocardial infarction. The hazard ratio (95% confidence interval) for acute myocardial infarction was 1.95 (1.42–2.68; P P for interaction=0.004, 0.004, and 0.03, respectively). Plasma dimethylglycine improved discrimination and reclassification and had high test–retest reliability. Conclusions— Plasma dimethylglycine is independently related to incident acute myocardial infarction and enhances risk prediction in patients with stable angina pectoris. Our results motivate further studies on the relationship between 1-carbon metabolism and atherothrombosis. A potential interplay with lipid and energy metabolism merits particular attention.

Total plasma homocysteine (tHcy) is an independent risk factor for coronary artery disease, and tHcy is lowered by B vitamins. To assess the effect of homocysteine-lowering B-vitamin treatment on angiographic progression of coronary artery disease, this substudy of the Western Norway B Vitamin Intervention Trial (WENBIT) included patients who had undergone percutaneous coronary intervention. The patients were randomized to daily oral treatment with folic acid, vitamin B(12), and vitamin B(6) or placebo in a 2 x 2 factorial design. The coronary angiograms obtained at baseline and follow-up were evaluated. The primary angiographic end points were the changes in minimum lumen diameter and diameter stenosis. A total of 348 subjects (288 men) with a mean +/- SD age of 60 +/- 10.2 years were followed up for a median of 10.5 months (twenty-fifth, seventy-fifth percentile 9.2, 11.8). The baseline median plasma tHcy level was 10.0 mumol/L (twenty-fifth, seventy-fifth percentile 8.1, 11.0), and treatment with folic acid/vitamin B(12) lowered the tHcy levels by 22%. At follow-up, we found 309 lesions with a significant decrease from baseline in the minimum lumen diameter of a mean of -0.16 +/- 0.4 mm and an increase in the diameter stenosis of 4.4 +/- 0.7%. Treatment with folic acid/vitamin B(12) or vitamin B(6) was not associated with a change in diameter stenosis or minimum lumen diameter. In a post hoc analysis, folic acid/vitamin B(12) treatment was significantly associated with rapid progression (odds ratio 1.84, 95% confidence interval 1.07 to 3.18). In conclusion, vitamin B treatment showed no beneficial effect on the angiographic progression of coronary artery disease, and the post hoc analyses suggested that folic acid/vitamin B(12) treatment might promote more rapid progression.

Background Loop diuretics are widely used in patients with heart and renal failure, as well as to treat hypertension and peripheral edema. However, there are no randomized, controlled trials (RCT) evaluating their long term safety, and several observational reports have indicated adverse effects. We sought to evaluate the impact of loop diuretics on long term survival in patients with suspected coronary artery disease, but without clinical heart failure, reduced left ventricular ejection fraction or impaired renal function. Method and Findings From 3101 patients undergoing coronary angiography for suspected stable angina pectoris, subjects taking loop diuretics (n=109) were matched with controls (n=198) in an attempted 1:2 ratio, using propensity scores based on 59 baseline variables. During median follow-up of 10.1 years, 37.6% in the loop diuretics group and 23.7% in the control group died (log-rank p-value 0.005). Treatment with loop diuretics was associated with a hazard ratio (95% confidence interval) of 1.82 (1.20, 2.76), and the number needed to harm was 7.2 (4.1, 30.3). Inclusion of all 3101 patients using propensity score weighting and adjustment for numerous covariates provided similar estimates. The main limitation is the potential of confounding from unmeasured patient characteristics. Conclusions The use of loop diuretics in patients with suspected coronary artery disease, but without systolic heart failure or renal impairment, is associated with increased risk of all-cause mortality. Considering the lack of randomized controlled trials to evaluate long term safety of loop diuretics, our data suggest caution when prescribing these drugs to patients without a clear indication. publishedVersion

of follow-up (PWV2). Samples for FGF-23 and 25(OH)D3 were determined cross-sectionally. Patients were divided into two groups cccording to 25(OH)D3 levels: Insufficiency (group 1, 25(OH)D3 30 ng/mL). Results: Patients in Group 1 (n: 91) had significantly higher annual mean values of phosphorus, CaxP product and FGF-23 compared to Group 2 (n: 26) (p < 0.018, 0.044 and 0.046, respectively). Administered elementary calcium dose was significantly higher in Group 1 than in Group 2 (p < 0.014). Patients in Group 1 had higher PWV1 and PWV2 measurements compared to Group 2 (p < 0.018 and 0.011). Serum levels of 25(OH)D3 were negatively correlated with mean phosphorus (p = 0.039) and mean administered elemantary calcium dose (P= 0.017). On multivariate analysis, levels of 25(OH)D3 were independently associated with the adjusted dose of elementary calcium (P< 0.002). Conclusion: Low level of 25(OH)D3 is not only a primary risk factor for cardiovascular health but might occur as a result of high phosphorus level or high cumulative calcium intake. While targeting to control renal osteodistrophy and achieving a higher 25(OH)D3 and lower FGF 23 for better outcome, better phosphorus control and minimum calcium supplementation should be the priority in the plan.

Background Virtual Histology Intravascular Ultrasound (VH–IVUS) may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1) is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment. Methods In a randomized, prospective study, 102 patients with stable angina pectoris (SAP) received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (±B6) or placebo (±B6) for 1 year before VH–IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA) in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI). Results Patients treated with folic acid/vitamin B12 had a geometric mean (SD) MCP-1 level of 79.95 (1.49) versus 86.00 (1.43) pg/mL for patients receiving placebo (p-value 0.34). VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47). Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92) times higher in patients with VH-TCFA lesions than in those without (p-value 0.005). Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI), which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006) and VH-TCFA (p-value 0.01). Conclusions In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. ClinicalTrials.gov Identifier: NCT00354081.