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Introduction and objectives: Cardiac involvement in systemic sclerosis (SSc) patients affects mortality. Cardiac magnetic resonance (CMR) is capable of detecting structural changes, including diffuse myocardial fibrosis that may develop over time. Our aim was to evaluate myocardial structure and function changes using CMR in patients with SSc without known cardiac disease during a 5-year follow-up and find possible correlations with selected biomarkers. Methods: A total of 25 patients underwent baseline and follow-up CMR examinations according to a pre-specified protocol. Standard biochemistry, five biomarkers (hsTnI, NT-proBNP, galectin-3, sST2, and GDF-15), and disease-specific functional parameters enabling the classification of disease severity were also measured. Results: After five years, no patient suffered from manifest heart disease. Mean extracellular volume (ECV) and T1 mapping values did not change significantly (p ≥ 0.073). However, individual increases in native T1 time and ECV correlated with increased galectin-3 serum levels (r = 0.56, p = 0.0050, and r = 0.71, p = 0.0001, respectively). The progression of skin involvement assessed using the Rodnan skin score and a decrease in the diffusing capacity of the lungs were associated with increased GDF-15 values (r = 0.63, p = 0.0009, and r = −0.51, p = 0.011, respectively). Conclusions: During the 5-year follow-up, there was no new onset of heart disease observed in patients with SSc. However, in some patients, CMR detected progression of sub-clinical myocardial fibrosis that significantly correlated with elevated galectin-3 levels. GDF-15 values were found to be associated with disease severity progression.

Patients with pulmonary embolism (PE) may have symptomatic or asymptomatic concomitant deep vein thrombosis (DVT). The reported prevalence of PE-associated DVT is variable, and thus, the utility of routine testing is controversial. The aim of our study was to analyze the prevalence of DVT and the factors associated with proximal DVT/whole-leg DVT in patients with symptomatic PE. In 428 consecutive patients (mean age: 59 ± 16.4 years; 52.3% men), we performed clinical examination and complete bilateral compression ultrasound and ascertained medical history and risk factors for DVT/PE. χ2 and t tests were used. Deep vein thrombosis was found in 70.6%; proximal DVT in 49.5%. Sensitivity/specificity of DVT symptoms was 42.7%/93.7% for whole-leg DVT and 47.6%/83.3% for proximal DVT. Male gender significantly prevailed among those with whole-leg DVT and with proximal DVT (58.9% and 61.8%). Active malignancy was significantly more frequent in the patients with proximal DVT than without proximal DVT (10.4% vs 3.7%). In conclusion, the prevalence of PE-associated DVT is quite high but clinical diagnosis is unreliable. In our group, male gender and active malignancy were significantly associated with the presence of concomitant proximal DVT.

A case–control study revealed association between hypertension and rs3918226 in the endothelial nitric oxide synthase ( eNOS ) gene promoter (minor/major allele, T/C allele). We aimed at substantiating these preliminary findings by target sequencing, cell experiments, and a population study. We sequenced the 140-kb genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected with the eNOS promoter carrying either the T or the C allele, we quantified transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0% women; mean age 40.1 years), we studied blood pressure change and incidence of hypertension in relation to rs3918226, using multivariable-adjusted models. Sequencing confirmed rs3918226, a binding site of E-twenty six transcription factors, as the single nucleotide polymorphism most closely associated with hypertension. In T compared with C transfected cells, eNOS promoter activity was from 20% to 40% ( P TT homozygotes and by 3.8/1.9 mm Hg in 2694 C allele carriers ( P ≤0.0004). The blood pressure rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6–11.1; P =0.028) and 4.8 mm Hg diastolic (CI, 1.5–8.2; P =0.0046) greater in TT homozygotes, with no differences between the CT and CC genotypes ( P ≥0.90). Among 2013 participants normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24–3.37; P =0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter tags a hypertension susceptibility locus, TT homozygosity being associated with lesser transcription and higher risk of hypertension.

Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

In line with Guyton s work, the goal of our research was to explore in t hree European populations whether the properties of large arteries are a ssociated with renal sodium handling, which itself changes with environm ental factors and with variation in a large number of genes. Before enga ging in the genetic analyses proper, we first studied the familial aggre gation and the heritability of arterial properties. In all our analyses, we accounted for relatedness among participants and for covariables and confounders. In a first study, we compared the arterial characteristics and blood pre ssure (BP) in normotensive offspring of two normotensive parents (OFF/NT ) and normotensive offspring, who had at least one hypertensive parent ( OFF/HT). We measured peripheral pulse pressure (PPp) by conventional and 24-h ambulatory BP. A SphygmoCor device was used to determine the centr al (CAIx) and peripheral (PAIx) systolic augmentation indexes, central p ulse pressure (PPc), and aortic pulse wave velocity (aPWV). Compared wit h OFF/NT (n=59; 16 to 34 years of age), the OFF/HT (n=174; 17 to 40 year s) had higher (0.14