In hypertensive subjects, the metabolic syndrome amplifies cardiovascular risk associated with high BP, independent of the effect of several traditional cardiovascular risk factors.

Background— Peripheral blood expansion of an unusual CD4+ T-cell subset lacking surface CD28 has been suggested to predispose rheumatoid arthritis (RA) patients to develop more aggressive disease. However, the potential association between CD4+CD28 null T cells and early atherosclerotic changes in RA has never been investigated. Methods and Results— The number of circulating CD4+CD28 null cells was evaluated in 87 RA and 33 control subjects who also underwent evaluation of carotid artery intima-media thickness (IMT) and endothelial function via flow-mediated vasodilation (FMV). Patients had higher IMT and lower FMV compared with control subjects. The frequency of CD4+CD28 null cells was significantly higher in patients than in control subjects. Twenty patients with persistent expansion of circulating CD4+CD28 null cells had more marked increase of carotid artery IMT and stronger decrease of brachial artery FMV. Blockade of tumor necrosis factor-α led to a partial reappearance of the CD28 molecule on the CD4+ cell surface. Conclusions— Circulating CD4+CD28 null lymphocytes are increased in RA. Patients with persistent CD4+CD28 null cell expansion show preclinical atherosclerotic changes, including arterial endothelial dysfunction and carotid artery wall thickening, more significantly than patients without expansion. These findings suggest a contribution of this cell subset in atheroma development in RA. Moreover, the demonstration that tumor necrosis factor-α blockade is able to reverse, at least in part, the CD28 deficiency on the CD4+ cell surface may be of interest for possible innovative therapeutic strategies in cardiovascular diseases.

Background Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. Methods Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. Results A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. Conclusions Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.

Impaired LV early diastolic relaxation, detected by pulsed Doppler echocardiography, identifies hypertensive patients at increased cardiovascular risk. Such association is independent of LV mass and ambulatory BP.

Background: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. Objective: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. Methods: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age (59 years), with DAS28 (3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls. Results: Mean (SD) FMV was significantly lower in patients than in controls Conclusions: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.

Metabolic syndrome is a powerful predictor of cardiovascular disease in hypertension, and large-artery stiffness is increasingly recognized as a cardiovascular risk factor. We hypothesized that the adverse prognostic significance of the metabolic syndrome in hypertension might be explained in part by its association with aortic stiffness. A total of 169 newly diagnosed, never treated, nondiabetic patients with essential hypertension (men 55%, 48+/-11 years) were classified by the presence (n=45) or absence (n=124) of the metabolic syndrome. All patients underwent aortic and upper limb pulse wave velocity determination by means of an applanation tonometry-based method. Aortic pulse wave velocity had a direct correlation with office and 24-hour systolic pressure (r=0.42 and 0.31, respectively), as well as with waist circumference (r=0.35, all P<0.001), but not with body mass index (r=0.10, P=not significant). Aortic pulse wave velocity was higher in the subgroup with the metabolic syndrome (10.0+/-2.7 versus 8.8+/-2.1 m/s; P=0.003), whereas upper limb velocity did not differ in the 2 groups (8.6+/-1.4 versus 8.7+/-1.5 m/s; P=not significant). In a multiple regression, aortic pulse wave velocity was independently associated with age, systolic blood pressure, and the metabolic syndrome. Only diastolic BP independently predicted upper limb pulse wave velocity. We conclude that in untreated hypertension, the metabolic syndrome is independently associated with a higher aortic, but not upper limb, pulse wave velocity. Central, but not general, adiposity is an important determinant of aortic stiffness in hypertension.

Objective. Systemic lupus erythematosus and rheumatoid arthritis represent independent risk factors for atherosclerosis (ATS), although this may be confounded by continuous pharmacologic treatment. Primary Sjögren's syndrome (SS) shares several features of these diseases and may therefore represent an interesting model for verifying the presence of accelerated ATS in the absence of pharmacologic interference. The present study therefore used this model to describe the presence of accelerated ATS in a group of young women.Methods. Thirty-seven untreated white women with primary SS were evaluated clinically and serologically. Carotid and femoral artery intima-media thickness (IMT) was evaluated in the patients and in 35 age-matched healthy women who served as controls.Results. The patients had a higher IMT than did the controls at both the carotid (mean ؎ SD 0.82 ؎ 0.24 mm versus 0.63 ؎ 0.20 mm; P < 0.001) and the femoral (0.81 ؎ 0.26 mm versus 0.67 ؎ 0.23 mm; P < 0.019) levels, and had a higher prevalence of carotid intimamedia thickening (49% versus 11% of controls; P < 0.001). The patient subset with high carotid IMT showed an increased prevalence of leukopenia and circulating anti-SSA antibodies; interestingly, the number of leukocytes was inversely correlated with the level of arterial IMT in patients with SS. Multivariate analysis demonstrated that anti-SSA antibodies were independent predictors of carotid artery thickening, while leukopenia was a predictor of both carotid and femoral artery thickening.Conclusion. Subclinical ATS was evident in about one-half of the patients with SS.

Abstract-Metabolic syndrome (MS) is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on left ventricular (LV) mass and function in the 2 genders has not been specifically addressed. Among 618 nondiabetic, untreated hypertensive subjects, echocardiographically detected LV mass was significantly greater in subjects with MS. A significant interaction was observed between sex and the MS (PϽ0.003 for the multiplicative interaction term). Compared with women without the MS, those with the syndrome had a 24% greater LV mass (49.5Ϯ12 versus 40.0Ϯ10 gϫm Ϫ2.7 ; PϽ0.001), whereas the difference was only 9% in men (50.3Ϯ12 versus 46.1Ϯ10 gϫm Ϫ2.7 ; Pϭ0.003). A greater prevalence of LV hypertrophy was found in women (37% versus 14%; PϽ0.001) but not in men (39% versus 29%; Pϭ0.09) with the MS. After adjustment for the effect of age, body mass index, 24-hour systolic blood pressure, and several confounders, the MS was independently associated with a greater LV mass index in women (regression coefficient, 4.80; PϽ0.001) but not in men. Women with the MS also had a greater LV relative wall thickness (0.42Ϯ0.07 versus 0.39Ϯ0.07; Pϭ0.004) and a depressed afterload-corrected midwall fractional shortening (94.0Ϯ12% versus 101.0Ϯ13%; PϽ0.001) than women without the syndrome, whereas no differences emerged in men. We conclude that, in untreated hypertension, MS has a different impact on LV hypertrophy and function in men and women. The effect of MS is more pronounced in women and is partly independent from the effect of several hemodynamic and nonhemodynamic determinants of LV mass. Key Words: hypertrophy Ⅲ remodeling Ⅲ metabolism Ⅲ gender Ⅲ risk factors T he metabolic syndrome (MS), a clustering of lipid and nonlipid cardiovascular risk factors, is increasingly recognized as an independent predictor of cardiovascular disease in hypertension. 1 The notion that the MS may have different relative importance for atherogenesis and cardiovascular disease in the 2 genders arises from observations indicating that elevated triglycerides and decreased high-density lipoprotein cholesterol, 2 basic components of the syndrome, are better predictors of the risk of adverse outcomes in women than in men. [2][3][4] Moreover, in those studies in which the prognostic impact of the MS has been examined separately in men and women, the coronary or cardiovascular morbidity/mortality hazard ratios associated with the syndrome were almost invariably found to be higher in the female sex. 1,5-10 Similarly, Iglseder et al 11 have observed in a healthy population that the effect of MS on carotid intimamedia thickness is more pronounced in women than in men.Left ventricular (LV) hypertrophy, a major manifestation of hypertensive heart disease, is a strong and independent herald for cardiovascular morbidity and mortality, 12,13 and its treatment-induced regression has been unequivocally associated with an improved cardiovascular prognosis, even after accounting for the confounding effect of treatment-induced b...