Association of BAFF and BAFF-R polymorphisms with sarcoidosis in a Greek patient cohort.

Introduction: Sarcoidosis is a disease that results from a combination of environmental and genetic factors. Its genetic basis however, is yet to be clarified. The purpose of this study is to determine whether single nucleotide polymorphisms (SNPs) of the B-cell activating factor (BAFF) and its receptor (BAFF-R) are associated with sarcoidosis. Material and methods: Blood samples from one hundred and seventy-three sarcoidosis patients and one hundred and sixty-four controls were collected. All samples were genotyped for BAFF rs2893321, rs1041569 and rs9514828, and for BAFF-R rs61756766. Results: Out of the three BAFF polymorphisms, none genotype had any significant association with sarcoidosis, although the T allele in rs1041569 and rs9514828 was overrepresented in sarcoidosis patients. A marginally significant association with sarcoidosis was found in the case of the CT genotype and T allele of BAFF-R rs61756766. Haplotype analysis of the BAFF polymorphisms was also performed, revealing an overrepresentation of the ATT, GTA and GTT haplotypes in the group of patients with cardiac involvement. Conclusions: Taken together, the results of this study suggest a possible relationship between BAFF SNPs, rs1041569 and rs9514828, and BAFF-R SNP rs61756766 with sarcoidosis susceptibility and their potential as biomarkers for the disease.

From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis.

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current "omics." The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis-even in clinically and physiologically silent sites-and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar-mediastinal nodal, (II) lungs and hilar-mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the "omics era," studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.

Co-occurrence between hereditary angioedema and multiple sclerosis: Therapeutic management of both diseases with fingolimod.

BACKGROUND: Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders, neurologic manifestations are rare. CASE REPORT: We report on the case study of a 33-year-old man diagnosed with HAE (SERPIN1G gene mutation) and multiple sclerosis (MS), followed up for at least 6 years. After a first clinical attack of HEA with scrotal edema, MS disease exacerbation was observed. Treatment with glatiramer acetate could not prevent either MS or HAE clinical attacks with recurrent exacerbations been observed. Remission of MS and significant amelioration of HAE attacks were achieved under fingolimod treatment. CONCLUSIONS: Herein we provide long term evaluation of an extremely rare case of concomitant existence of HAE and MS and present the effects of MS current disease-modifying therapies in HAE attacks. Our case highlights the possible effect of fingolimod in immunoregulatory-mechanisms implicated in both diseases.

Peripheral blood natural killer cells in sarcoidosis are associated with early cardiac involvement.

AIM: To evaluate the distribution of circulating immune cell subsets in peripheral blood of patients with sarcoidosis and investigate if there is an association with an underlying cardiac involvement. METHODS AND RESULTS: Eighty-five newly diagnosed treatment-naïve patients with sarcoidosis (50 women) were included in the study. All patients underwent a thorough cardiac investigation, including cardiac magnetic resonance imaging (CMR). Of all patients, 19 (23.53%) had myocardial involvement, and the NK subpopulation in these patients in peripheral blood was significantly decreased compared to patients without (n = 63, p = 0.001 and p = 0.003 respectively). The absolute number of NKT cells (CD3+CD16/56+ ) in patients with cardiac involvement was highly correlated with T2 map increased values in MRI (r = -686, p = 0.041) showing that low NKT cell count correlates with the inflammatory process of the heart. No difference in CD19, CD3, CD4, CD8 and CD3- NK cell counts was found between groups. Lung severity was not found to correlate with the number of NK cells. CONCLUSION: We found that low NK cell count in peripheral blood of patients with sarcoidosis is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of myocardial inflammation. This finding might have a potential clinical application in detecting clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions.

Cardiopulmonary exercise testing and prognosis in patients with systemic sclerosis without baseline pulmonary hypertension: a prospective cohort study.

Cardiopulmonary Exercise Testing (CPET) is a standardized, non-invasive procedure assessing pulmonary, cardiovascular, hematopoietic, and skeletal muscle functions during a symptom-limited test. Few studies have examined whether CPET is of prognostic value in Systemic Sclerosis (SSc), a disease characterized by highly increased cardiorespiratory morbidity and mortality. To examine the prognostic value of CPET in SSc patients without baseline pulmonary hypertension (PH). Sixty-two consecutive SSc patients underwent CPET, Pulmonary Function Tests (PFTs) and echocardiography at baseline. Four patients with Right Ventricular Systolic Pressure ≥ 40 mmHg, were excluded. Participants repeated PFTs approximately every 3 years. At the end of the follow-up period [median (IQR): 9.79 (2.78) years] patient vital status was recorded. Cox Regression analysis was used to identify predictors of deterioration of PFTs and 10-year survival. Median (IQR) age of 58 patients (90% women) at baseline was 54.0 (15.0) years, whereas 10-year survival was 88%. Baseline respiratory Oxygen uptake (VO2max) predicted PFT deterioration, defined either as a decline in FVC ≥ 10% or a combined decline in FVC 5%-9% plus DLCO ≥ 15%, during follow-up, after correction for age, gender and smoking status (HR: 0.874, 95%CI: 0.779-0.979, p = 0.021). In addition, lower baseline VO2max (HR = 0.861, 95%CI:0.739-1.003, p = 0.054) and DLCO (HR = 0.957, 95%CI: 0.910-1.006 p = 0.088), as well as male gender (HR = 5.68, 95%CI: 1.090-29.610 p = 0.039) and older age (HR = 1.069, 95%CI: 0.990-1.154, p = 0.086) were associated, after adjustment, with an increased risk for death. In the absence of baseline PH, CPET indices may predict pulmonary function deterioration and death in SSc patients during a nearly 10-year follow-up period.

IgG4-related autoimmune manifestations in Alemtuzumab-treated multiple sclerosis patients.

We aimed to determine whether Alemtuzumab-induced immune reconstitution affects immunoglobulin and complement levels in the serum of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. IgG4-levels were increased 24-months after treatment initiation compared to baseline levels in twenty-nine patients. Alemtuzumab-treated patients with the highest IgG4-levels were more prone to thyroid-related autoimmune manifestations and specific autoimmune adverse events such as Crohn's disease, Graves' disease, and hemolytic anemia. Compared to baseline, total IgG-levels showed a trend towards reduced levels following two-courses of Alemtuzumab, but no significant change of C3 and/or C4-levels was observed. In conclusion, monitoring of IgG4-levels can serve as a marker for secondary autoimmunity risk in multiple sclerosis patients treated with Alemtuzumab.

Clinico-radiologic features and therapeutic strategies in tumefactive demyelination: a retrospective analysis of 50 consecutive cases.

AIMS: Our goal was to expand the spectrum of clinico-radiologic characteristics and the possible therapeutic choices in patients with tumefactive demyelinating lesions (TDLs). METHODS: A retrospective analysis of 50 patients with at least one TDL was performed at an academic neurology center (2008-2020). RESULTS: Our cohort comprised mostly women (33/50) with a mean age of 38 years at TDL onset. The mean follow-up time was 76 months. The mean Expanded Disability Status Scale score at TDL onset and at the latest neurological evaluation was 3.7 and 2.3, respectively. We subcategorized the patients into seven groups based mainly on the clinical/radiological findings and disease course. Group A included patients presenting with a Marburg-like TDL (n = 4). Groups B and C comprised patients presenting with monophasic (n = 7) and recurrent TDLs (n = 12), respectively. Multiple sclerosis (MS) patients who subsequently developed TDL (n = 16) during the disease course were categorized as Group D. Group E comprised patients who initially presented with TDL and subsequently developed a classical relapsing-remitting MS without further evidence of TDL (n = 5). Groups F (n = 2) and G (n = 4) involved MS patients who developed TDL during drug initiation (natalizumab, fingolimod) and cessation (interferon, fingolimod), respectively. Regarding long-term treatments applied after corticosteroid administration in the acute phase, B-cell-directed therapies were shown to be highly effective especially in cases with recurrent TDLs. Cyclophosphamide was spared for more aggressive disease indicated by a poor response to corticosteroids and plasma exchange failure. CONCLUSION: Tumefactive central nervous system demyelination is an heterogenous disease; its stratification into distinct groups according to different phenotypes can establish more efficient treatment strategies, thus improving clinical outcomes in the future.

Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature.

Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

X-linked dilated cardiomyopathy: the important role of genetic tests and imaging in the early diagnosis and treatment.

Familial dilated cardiomyopathy predominantly affects younger adults and may cause advanced heart failure and sudden cardiac death. Therefore, detailed family history, family members screening, appropriate genetic testing and counselling may allow correct identification of cardiac remodeling etiology, as well as earlier disease detection. Accordingly, we present a case with an early diagnosis of an X-linked dilated cardiomyopathy guided by clinical features, cardiac MRI and genetic testing. The diagnostic workup was guided by the positive family history of cardiomyopathy and sudden cardiac deaths. Clinical implications including early management, better arrythmia risk stratification and the revealing of a potential endemic entity clustering in several male subjects of a community on Crete island are further discussed.

Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.

Blood Pressure Deviation from the Golden Ratio φ and All-cause Mortality: A Pythagorean View of the Arterial Pulse.

INTRODUCTION: There is one mathematical element with strong historical and philosophical background that exhibits remarkable properties and applications; the golden ratio (phi). Mathematically, the golden ratio equals approximately 1.61803. A rather provocative geometrical analysis of the arterial pulse according to the golden ratio was recently described, and herein, we aim to set out the hypothesis that individuals with blood pressure (BP) values that follow the golden ratio may have different prognosis than those whose BPs deviate from the divine proportions. MATERIALS AND METHODS: We used published data from the National Health and Nutrition Examination Survey during 1999-2010. RESULTS: We found that the deviation of the BP values from the golden ratio is independently associated with all-cause mortality. CONCLUSIONS: This observation stimulates further research of the potential utility of the golden ratio of BP values on the diagnosis and prediction of BP-related abnormalities and risk.

Global longitudinal strain and long-term outcomes in asymptomatic extracardiac sarcoid patients with no apparent cardiovascular disease.

PURPOSE: Global longitudinal strain (GLS) is increasingly accepted as a predictor of mortality in various clinical settings. This study tested the hypothesis that GLS is associated with increased event rate in patients with extracardiac sarcoidosis, who have no overt symptoms of cardiovascular disease and preserved ejection fraction (EF). METHODS: We retrospectively studied 117 patients with extracardiac sarcoidosis and 45 age- and sex-matched controls, who underwent comprehensive echocardiographic study, while GLS was measured by an offline speckle tracking algorithm. Patients who had signs and symptoms of cardiovascular disease at the time of the examination were excluded from the study. Patients were followed for an average of 57.1 months. Primary endpoint was defined as a composite endpoint of heart failure-related hospitalizations, need for device therapy, arrhythmias, and all-cause mortality. RESULTS: The age of patients was 42 ± 6 years old (43 men). Events were recorded in 10 patients (8.5%). Tissue Doppler revealed E/Em 7.9 ± 3.5, while EF was 54.2 ± 3.5%. Global longitudinal strain was 14.4 ± 3%, and a cutoff value ≤-13.6% for GLS was considered more associated with adverse outcomes (AUC 0.84). After adjustment for multiple potential confounders (age, gender, hypertension, diabetes, E/Em, and EF), GLS remained strongly associated with adverse outcomes (HR 0.8, 0.63 to 0.98 95% C.I, P = .04). CONCLUSIONS: In conclusion, among patients with extracardiac sarcoidosis and no symptoms of cardiovascular disease, even when EF is preserved, GLS seems to be strongly associated with adverse future events.

Myocardial strain may predict exercise tolerance in patients with reduced and mid-range ejection fraction.

BACKGROUND: Conventional echocardiographic parameters, such as rest ejection fraction, perform poorly in the prediction of exercise tolerance in heart failure. The aim of the present study was to evaluate the contribution of hemodynamic instability in the observed lower functional capacity and investigate the role of left ventricular strain for the prediction of stress test duration in obese hypertensive patients with reduced ejection fraction. METHODS: Sixty-one patients with reduced ejection fraction underwent treadmill exercise echocardiography. Systolic and diastolic echocardiographic parameters were recorded. Moreover, the presence of hemodynamic instability was assessed through N-terminal pro B-type natriuretic peptide (NT-proBNP) measurements at baseline and peak exercise. RESULTS: Rest and peak NT-proBNP levels, and their difference, were significantly correlated with mean global strain at peak, which was the only parameter associated with changes in NT-proBNP levels. Rest and peak mean global strain were found to be predictive for the duration of treadmill stress test. In particular, mean global strain, but not left ventricular ejection fraction, was independently correlated with exercise ability. CONCLUSIONS: Stress echocardiography may provide important information regarding exercise tolerance in obese hypertensive patients with reduced ejection fraction, mainly through the evaluation of left ventricular strain. The obtained evidence may also have prognostic value, particularly in the early stages of the syndrome.

Complementary Role of CMR to Conventional Screening in the Diagnosis and Prognosis of Cardiac Sarcoidosis.

OBJECTIVES: The goal of this study was to assess the independent and collective diagnostic value of various modalities in cardiac sarcoidosis, delineate the role of cardiac magnetic resonance (CMR), and identify patients at risk. BACKGROUND: Cardiac sarcoidosis is associated with increased morbidity and mortality. CMR is a key modality in the evaluation of patients with cardiac symptoms, but the complementary role of CMR to conventional tests for the diagnosis of cardiac sarcoidosis is not fully defined. METHODS: Patients (N = 321) with biopsy-proven sarcoidosis underwent conventional cardiac testing and CMR with late gadolinium enhancement (LGE) and were followed up for primary (composite of all-cause mortality, sustained ventricular tachycardia [VT] episodes, or hospitalization for heart failure) and secondary (nonsustained VT episodes) endpoints. RESULTS: Cardiac sarcoidosis was diagnosed in 29.9% of patients according to the Heart Rhythm Society consensus criteria. CMR was the most sensitive and specific test (area under the curve: 0.984); it detected 44 patients with cardiac symptoms and/or electrocardiogram (ECG) abnormalities but normal echocardiogram, as well as 15 asymptomatic patients with normal baseline testing. Echocardiography added to cardiac history and ECG did not change sensitivity of the initial screening strategy (68.8% vs. 72.9%). Despite a high positive predictive value (83.9%), echocardiography had a low sensitivity (27.1%). During follow-up, 7.2% of patients reached the primary endpoint and another 3.4% reached the secondary endpoint. LGE was and independent predictor of primary endpoints (hazard ratio: 5.68; 95% CI: 1.74 to 18.49; p = 0.004). LGE, age, and baseline nonsustained VT were independent predictors of all events. In patients with cardiac symptoms and/or an abnormal ECG, CMR increased diagnostic accuracy and independently predicted primary endpoints (hazard ratio: 12.71; 95% confidence interval: 1.48 to 109.35; p = 0.021). CONCLUSIONS: Of all cardiac tests, CMR was the most valuable in the diagnosis and prognosis of cardiac sarcoidosis in a general sarcoidosis population. Echocardiography had an overall limited diagnostic value as a screening test, and an abnormal study, despite a high positive predictive value, may still need confirmation with CMR.

Cardiovascular magnetic resonance imaging pattern at the time of diagnosis of treatment naïve patients with connective tissue diseases.

BACKGROUND-AIM: Cardiac involvement at diagnosis of connective tissue disease (CTD) has been described by echocardiography. We hypothesized that cardio-vascular magnetic resonance (CMR) detects occult lesions at CTD diagnosis. PATIENTS-METHODS: CMR was performed early after diagnosis in 78 treatment-naïve CTDs (aged 43±11, 59F/19M) without cardiac involvement [5 Takayasu arteritis (TA), 4 Churg Strauss syndrome (CSS), 5 Wegener granulomatosis (WG), 16 systemic lupus erythematosus (SLE), 12 rheumatoid arthritis (RA), 8 mixed connective tissue diseases (MCTD), 12 ankylosing spondylitis (AS), 3 polymyalgia rheumatica (PMR), 8 systemic sclerosis (SSc) and 5 dermatomyositis (DM)]. Acute and chronic lesions were assessed by T2>2 with positive LGE and T2<2 with positive LGE, respectively. RESULTS: In 3/5 TA, 3/4 CSS, 4/5 WG, 10/16 SLE, 9/12 RA, 6/8 MCTD, 4/12 AS, 1/3 PMR, 2/8 SSc and 2/5 DM, the T2 ratio was higher compared to normal (2.78±0.25 vs 1.5±0.2, p<0.01). Myocarditis was identified in 1 TA, 1 SLE, 1 RA, 1 SSc and 2 DM patients; diffuse, subendocardial fibrosis in 1 CSS and 1 RA patient, while subendocardial myocardial infarction in 3 SLE, 1 MCTD, 1 PMR and 2 RA patients. CMR re-evaluation after 6 and 12months of rheumatic and cardiac treatment, available in 28/52 CTDs with increased T2 ratio, showed significant improvement in T2 ratio (p<0.001), non-significant change in LGE extent and normalisation of those with impaired LV function. CONCLUSIONS: Occult CMR lesions, including oedema, myocarditis, diffuse subendocardial fibrosis and myocardial infarction are not unusual in treatment naïve CTDs and may be reversed with appropriate treatment.

The APOE E4 Allele Confers Increased Risk of Ischemic Stroke Among Greek Carriers.

BACKGROUND: Although several studies in various countries have indicated that the presence of the E4 allele of the apolipoprotein-E (APOE) gene is a risk factor for ischemic cerebrovascular disease, the strength of this association still remains a matter of debate. OBJECTIVES: The aim of the study was to determine the frequency of the APOE E4 allele and various other gene polymorphisms in in a well-characterized sample of Greek patients and to evaluate the potential associations with the risk of ischemic stroke (IS) and coronary heart disease (CHD). MATERIAL AND METHODS: A total of nine gene variants/polymorphisms - F5 (Leiden - R5 06Q, rs6025), F2 (20210G > A, rs1799963), F13A1 (V34L, rs5985), MTHFR (677C > T - A222V, rs1801133), MTHFR (1298A > C - E429A, rs1801131), FGB (-455G > A -c.-463G > A; rs1800790), SERPINE1 (PAI14G/5G - rs1799889), ACE (ACE I/D, rs1799752), ITGB3 (GPIIIa L33P, rs5918) and the APOE E2/E3/E4 alleles (rs7412, rs429358) - were genotyped in 200 newly diagnosed ischemic stroke (IS) patients, 165 patients with ischemic coronary heart disease (CHD) and 159 controls with no cerebroor cardiovascular disease (non-CVD). A statistical analysis was performed using univariate and multivariate logistic regression models. RESULTS: No significant association was found regarding most gene polymorphisms and the presence of IS or CHD in the patient cohort. However, the APOE E4 allele frequency was significantly higher (p = 0.02) among patients with ischemic stroke (IS) or IS + CHD (12.7%) when compared to the controls (5.1%). More accurately, E4 carriers had 2.66 and 2.71 times greater likelihood of IS or IS + CHD than non-carriers, respectively (OR = 2.66, 95% CI 1.39-5.07, OR = 2.71, 95% CI 0.98-7.48). CONCLUSIONS: In contrast to some previous studies, these results support the role of the APOE E4 allele as an independent risk factor for ischemic stroke and ischemic coronary heart disease among Greek patients.

Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals.

To assess the differences among seven different methods for the calculation of mean arterial pressure (MAP) and to identify the formula that provides MAP values that are more closely associated with target organ deterioration as expressed by the carotid cross-sectional area (CSA), carotid-to-femoral pulse-wave velocity (cf-PWV) and left ventricular mass (LVM). The study population consisted of 1878 subjects who underwent noninvasive cardiovascular risk assessment. Blood pressure (BP) was assessed in all subjects, and MAP was calculated by direct oscillometry and six different formulas. Carotid artery ultrasound imaging was performed in 1628 subjects. The CSA of the right and left common carotid artery (CCA) were calculated and used as surrogates of arterial wall mass and hypertrophy. Aortic stiffness was evaluated in 1763 subjects by measuring the cf-PWV. Finally, 218 subjects underwent echocardiographic examination for the assessment of LVM. Among the examined methods of MAP calculation, the formula MAP1=[diastolic BP]+0.412 × [pulse pressure] yielded the strongest correlations with the LVM, cf-PWV and CSA of the right and left CCA, even after adjusting for age and gender. The MAP calculation using the 0.412 was superior compared with the traditional formula that uses the 0.33 for the discrimination of subjects with left ventricular and carotid wall hypertrophy, as well as subjects with increased aortic stiffness. MAP estimated with the 0.412 is better correlated with target organ deterioration compared with other formulas. Future studies are needed to explore the accuracy of these formulas for MAP estimation compared with direct intra-arterial BP measurement.