Objective— The extent to which atherosclerosis is accelerated in chronic inflammatory diseases is not established. We compared preclinical atherosclerosis in rheumatoid arthritis with diabetes mellitus, a known coronary heart disease equivalent. Methods and Results— Endothelial function, arterial stiffness, carotid intima-media thickness, and analysis of atheromatous plaques were examined in 84 rheumatoid arthritis patients without cardiovascular disease versus healthy controls matched for age, sex, and traditional cardiovascular disease risk factors, as well as in 48 diabetes patients matched for age, sex, and disease duration with 48 rheumatoid arthritis patients. Rheumatoid arthritis duration associated with arterial stiffening, whereas disease activity associated with carotid plaque vulnerability. All markers of preclinical atherosclerosis were significantly worse in rheumatoid arthritis compared to controls, whereas they did not differ in comparison to diabetes despite a worse cardiovascular risk factor profile in diabetics. Both diseases were associated independently with increased intima-media thickness; rheumatoid arthritis, but not diabetes, was independently associated with endothelial dysfunction. Conclusions— Preclinical atherosclerosis appears to be of equal frequency and severity in rheumatoid arthritis and diabetes of similar duration with differential impact of traditional risk factors and systemic inflammation. Cardiovascular disease risk factors in rheumatoid arthritis may need to be targeted as aggressively as in diabetes.

Hyperprolactinemia has been associated with endothelial dysfunction and an adverse cardiovascular risk profile, possibly as a result of the vasoconstrictive properties of prolactin. In this cross-sectional study, we examined the hypothesis that prolactin contributes to the increased cardiovascular risk occurring in early menopause by studying apparently healthy women without hyperprolactinemia. Prolactin serum levels were measured by immunoassay in 76 women aged 54.4±4.9 years in menopause for 4.9±2.8 years, and possible correlations with traditional cardiovascular risk factors and surrogate markers of preclinical atherosclerosis, arterial stiffening, and endothelial and microcirculatory function were examined. Positive correlations between prolactin serum levels and arterial blood pressure, but no other traditional risk factors, were found. Prolactin also correlated with central aortic systolic ( r =0.337; P =0.002) and diastolic ( r =0.272; P =0.012) blood pressures and pulse wave velocity ( r =0.264; P =0.02), a marker of aortic stiffness, but not with endothelial or microcirculatory function or carotid intima-media thickness. By multivariate regression analysis, prolactin levels determined, independent of traditional risk factors, both blood pressures and aortic stiffness. Notably, prolactin correlated with European Society of Cardiology HeartScore ( r =0.364; P =0.002), a composite index that predicts 10-year cardiovascular mortality. Prolactin levels >8.0 ng/mL had 100% sensitivity to predict a high peripheral blood pressure. Prolactin may play a role in accelerated arteriosclerosis in early menopause by affecting central/peripheral blood pressure and arterial stiffness. In contrast, no correlation was observed with other risk factors or surrogate markers of atherosclerosis. Prospective studies to assess whether prolactin is an additional hormone increasing cardiovascular risk are warranted.

Bortezomib and dexamethasone with cyclophosphamide (CyBorD) or melphalan (BMDex) are commonly used primary treatments for light-chain (AL) amyloidosis, but limited data exist on bortezomib with immunomodulatory drug combinations. We report our experience with primary therapy with a bortezomib, lenalidomide, and dexamethasone (VRD) “light” regimen in 34 consecutive patients with AL amyloidosis. The majority (79%) had cardiac involvement, 15% and 23% were Mayo stage 3A and 3B, respectively, and 54% had renal involvement. After the first VRD cycle, 71% of patients achieved a hematologic response (44% at least very good partial response [VGPR]). On intent to treat, 11 (32%) achieved a complete response (of whom 5 of 11 were minimal residual disease [MRD] negative at 10⁻⁵), 17 (50%) a VGPR, and 2 (7%) a partial response. The 12-month survival was 73%. Starting lenalidomide dose was 5 mg in 86% of patients. Hematologic toxicity was mild; nonhematologic toxicities included rash (grade 3/4 [16%]), infections (grade ≥3 [12%]), constipation (grade ≥3 [9%]), and peripheral neuropathy (grade 2 [20%]); 37.5% of patients required lenalidomide dose reduction, 27% discontinued lenalidomide, 38% required bortezomib dose reduction, and 12% discontinued bortezomib. We compared VRD to CyBorD in 68 patients matched for Mayo stage and baseline difference between involved minus uninvolved serum free light chain levels, and observed a trend for deeper response at 3 and 6 months with VRD. In conclusion, VRD can be an active regimen for newly diagnosed patients with AL amyloidosis able to induce very deep hematologic responses at the expense of increased toxicity.

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.