Sarcopenia in Rheumatoid arthritis. A narrative review.

Sarcopenia was recently identified as an entity in the ICD-10 classification of October 2016. According to the recommendation of the European Working Group on Sarcopenia in Older People (EWGSOP2), sarcopenia is defined as low muscle strength and low muscle mass, while physical performance is used to categorize the severity of sarcopenia. In recent years, sarcopenia has become increasingly common in younger patients with autoimmune diseases such as Rheumatoid arthritis (RA). Due to the chronic inflammation caused by RA, patients have reduced physical activity, immobility, stiffness, and joint destruction and all of that lead to the loss of muscle mass, muscle strength, disability and significantly lowering the patients' quality of life. This article is a narrative review about sarcopenia in RA, with a special focus in its pathogenesis and management.

Aortic stiffness and systemic inflammation changes predict clinical response to intravitreal anti-vascular endothelial growth factor therapy in patients with age-related macular degeneration.

Aortic stiffness and systemic inflammation are predictors of cardiovascular risk. Anti-vascular endothelial growth factor agents (anti-VEGF), injected intravitreally, can reverse the course of exudate age-related macular degeneration (AMD). We sought to investigate the association of changes in aortic stiffness and systemic inflammation with response to anti-VEGF therapy. 54 patients (mean age: 76 ± 10 years) with AMD received two consecutive monthly intravitreal injections of ranibizumab (0.5 mg). The primary outcome measure was change in carotid-femoral pulse wave velocity (PWV) from baseline to 1 month after the second injection. Secondary endpoint was the change in serum high sensitivity interleukin-6 (hsIL-6) levels. Ranibizumab caused a decrease of PWV after the first (by 0.36 ± 1.4 m/s) and the second injection (by 0.31 ± 1.4 m/s) and remained decreased 1 month after the second injection (overall P < 0.05). PWV decreased significantly in good responders (according to clinical criteria and fundus findings, P = 0.004), whereas it increased numerically in poor responders (P = 0.21) over the study period. In responders, hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 ± 0.35 pg/ml, overall P = 0.02). PWV (P = 0.005) and hsIL-6 (P = 0.042) were independent predictors of improvement after adjusting for age and presence of hypertension and diabetes. The decrease in PWV through the whole study period was positively correlated with the reduction in hsIL-6 (r = 0.36, P < 0.01). Intravitreal ranibizumab injections lead to a decrease in PWV and hsIL-6. Both parameters predict clinical improvement and may aid to improving treatment targeting and hence therapeutic outcome in patients with AMD.

The effect of an mRNA vaccine against COVID-19 on endothelial function and arterial stiffness.

To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

MicroRNAs as Biomarkers in Hypertrophic Cardiomyopathy: Current State of the Art.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis that contributes to heart failure, arrhythmias and sudden cardiac death. OBJECTIVE: Currently, there are no reliable serum biomarkers for the detection of myocardial fibrosis, while cardiac magnetic resonance (CMR) is an imaging technique to detect myocardial fibrosis. MicroRNAs (miRNAs) have been increasingly suggested as biomarkers in cardiovascular diseases. However, in HCM there is as yet no identified and verified specific circulating miRNA signature. METHODS: We conducted a review of the literature to identify the studies that indicate the possible roles of miRNAs in HCM. RESULTS: From studies in transgenic mice with HCM, miR-1, -133 may identify HCM in the early asymptomatic phase. Human miR-29a could be used as a circulating biomarker for detection of both myocardial hypertrophy and fibrosis in HCM, while it could also have a possible additional role in discrimination of hypertrophic obstructive cardiomyopathy from non-obstructive HCM. Additionally, miR-29a-3p is associated with diffuse myocardial fibrosis in HCM, while miR-1-3p could discriminate end-stage HCM from dilated cardiomyopathy and left ventricle dilation. Another role of miRNAs could also be the contribution in the differential diagnosis between HCM and phenocopies. Moreover, miRNA- targeted therapy (miR-133 mimics) is promising in inhibiting cardiac hypertrophy, but this is still in the early stages. CONCLUSION: A more reliable and specific signature of miRNAs is expected with forthcoming studies in samples from HCM patients and correlation of miRNAs with CMR and serum markers of fibrosis may implicate novel diagnostic and therapeutic pathways.

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.

Effect of Ticagrelor Versus Clopidogrel on Aortic Stiffness in Patients With Coronary Artery Disease.

Background We compared the acute and midterm effect of ticagrelor versus clopidogrel on aortic stiffness. Methods and Results We studied 117 patients in a randomized, assessor-blinded, parallel-group trial. The acute effect of ticagrelor was studied in 58 patients randomized (1:1) to receive a loading dose of clopidogrel (600 mg) or ticagrelor (180 mg). Carotid-femoral pulse wave velocity (cf PWV ) was measured before, 3, and 24 hours after the loading dose. The midterm effect (30-day treatment period) was studied in 59 subjects who underwent percutaneous coronary intervention and were randomized to either clopidogrel (75 mg, OD) or ticagrelor (90 mg BID). cf PWV was measured before and at 30 days of treatment. Circulating markers of inflammation and endothelial function were measured at all study points. Repeated-measures analysis showed a significant main effect for treatment ( P=0.03), with the ticagrelor showing a reduction in cf PWV after treatment. cf PWV at 24 hours was significantly lower in the ticagrelor group compared with the clopidogrel group ( P=0.017) (maximal response reduction by 0.42±0.26 m/s). At 30 days, cf PWV decreased in the ticagrelor group, whereas there was no change with clopidogrel (-0.43±0.57 versus 0.12±0.14 m/s, P=0.004). There were no significant changes in both the acute and midterm study period in the pro-inflammatory and endothelial function parameters. Conclusions URL : https://www.clinicaltrials.gov . Unique identifier: NCT02071212. Ticagrelor decreases cf PWV for 24 hours after the loading dose and at 1 month post-percutaneous coronary intervention compared with clopidogrel. Considering that aortic stiffness is an independent predictor of cardiovascular events, this finding may have clinical implications regarding the beneficial effect of ticagrelor. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT02071212.

Biomarkers of Atrial Fibrillation in Metabolic Syndrome.

Whether the increased atrial fibrillation (AF) risk in metabolic syndrome (MetS) patients is due to the syndrome as a whole or simply the sum of the risks of its individual component parts is still obscure. These two clinical entities share many pathophysiological links and thus distinction between a casual observation and a significant association is difficult. Biomarkers associated with pathogenesis of AF in the context of MetS have the ability to refine future risk prediction. In the present review we identify circulating substances that could be regarded as potential biomarkers for prediction of incident AF, or of cardiovascular events in the setting of AF in patients with MetS. Cardiac myocyte injury and stress markers (troponin and natriuretic peptides), markers of renal function (glomeral filtration rate, cystatin-C), and inflammation markers/mediators (interleukin- 6, CRP) are promising biomarkers of patients with AF and MetS.

Diagnostic modalities in peripheral artery disease.

Peripheral artery disease (PAD) affects approximately one in five persons older than 70 years of age and it is often present in patients with concomitant vascular disease in different body territories (e.g. coronary artery disease). Diagnosis at an early stage is important in order to achieve improvement in patient's symptoms and prognosis. Remarkable improvements in the field of noninvasive and invasive imaging techniques have led to an advanced level the management of patients with PAD. Throughout this review article, the clinically available diagnostic modalities in PAD are presented. Strong and weaker points are stressed out in a manner that elucidates that no perfect diagnostic method exists. Based on the patient's individual profile, as well as on certain aspects of the disease (e.g. morphology of carotid plaque lesions) the attending physician will ultimately decide which diagnostic path will lead to a prompt and correct diagnosis of PAD with the minimum amount of exams and risk for the patient.

Acute effect of coffee on aortic stiffness and wave reflections in healthy individuals: differential effect according to habitual consumption.

The acute effect of coffee on arterial stiffness and its dependence on habitual consumption was studied in 24 volunteers on four separate occasions during which subjects received: (a) coffee espresso, (b) decaffeinated coffee espresso, (c) caffeine alone and (d) placebo (hot water). The increase in carotid femoral pulse wave velocity (PWV), augmentation index (AIx) and augmented pressure (AP) of the aortic pressure waveform after coffee consumption was more pronounced in non-habitual (n = 13) compared to habitual drinkers (n = 11), (differences of maximal changes between groups in PWV, AIx, AP responses by 0.39 m/s, 4.5% and 1.9 mmHg, respectively, for coffee; and by 0.34 m/s, 5.3% and 2.1 mmHg, respectively, for decaffeinated coffee; all p < .05). Caffeine increased PWV, as well as AIx and AP but differences in responses between the two groups were not significant. Both caffeinated and decaffeinated coffee consumption is associated with a more potent effect on arterial stiffness in non-habitual than habitual coffee consumers, whereas caffeine induces comparable changes in both groups.

Statin Therapy and Risk of Diabetes Mellitus in Aging Patients With Heterozygous Familial Hypercholesterolemia or Familial Combined Hyperlipidemia: A 10-Year Follow-Up.

We assessed the incidence of diabetes mellitus (DM) in patients with heterozygous familial hypercholesterolemia (HeFH) and familial combined hyperlipidemia (FCH) treated with statins. Participants (n = 280) of mean age 59 ± 5 years were included (90 patients with HeFH, 112 patients with FCH, and 78 aged-matched participants). The median statin intensity treatment product (statin intensity in arbitrary equivalence units × duration of statin therapy in months) was 119 and 85 for patients with HeFH and FCH, respectively, at 10-year follow-up. The incidence of DM was significantly lower in patients with HeFH compared to the patients with FCH (2% vs 20%) and the reference group (2% vs 17%) during the 10-year follow-up period (all Ps < .001). Impaired fasting blood glucose at entry ( P < .001) and central obesity ( P = .02) were the only independent predictors of DM. The incidence of DM was significantly lower in older patients with HeFH compared to either aged-matched patients with FCH or individuals not receiving statins. Statins did not increase risk of DM in aging patients with FCH. These findings have implications, given the importance of high-intensity statin therapy for prevention of cardiovascular events, especially in patients with HeFH, a population with high cardiovascular risk.

Cardiovascular Risk Factors Accelerate Progression of Vascular Aging in the General Population: Results From the CRAVE Study (Cardiovascular Risk Factors Affecting Vascular Age).

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular risk. We hypothesized that the number of cardiovascular risk factors determines the progression of vascular aging. One hundred forty-two subjects (mean age 51.9 years, 94 men) without established cardiovascular disease were investigated in 2 examinations over a 2-year period. Subjects were classified at baseline according to their number of risk factors (from 0 to 2 and more). Subjects had determinations of carotid-femoral pulse wave velocity, aortic augmentation index, brachial flow-mediated dilatation, and common carotid intima-media thickness and their annual absolute changes were calculated. Subjects with more risk factors had a gradual higher annual progression of pulse wave velocity (0.092 m/s/y for 0, 0.152 m/s/y for 1, and 0.352 m/s/y for 2 and more; P=0.007). Patients with both hypertension and dyslipidemia have 4× higher annual progression rate compared with subjects without these risk factors (0.398 m/s/y versus 0.102 m/s/y). When only subjects 55 years old and under were considered, the progression rate of augmentation index was higher in subjects with more risk factors (1.15%/y versus 1.50%/y versus 2.99%/y, respectively; P=0.037). No association was found with the annual change of flow-mediated dilatation or carotid intima-media thickness. In the general population, increasing number of risk factors is associated with accelerated deterioration of specific indices of vascular aging, such as pulse wave velocity and augmentation index; in contrast, flow-mediated dilatation and carotid intima-media thickness are insensitive to such changes. Accordingly, the former may be more useful for gauging vascular aging.

Central Haemodynamics and Prediction of Cardiovascular Events in Patients With Erectile Dysfunction.

BACKGROUND: We investigated whether central hemodynamics predict major adverse cardiovascular events (MACEs) in erectile dysfunction (ED) patients beyond traditional risk factors. METHODS: MACEs in relation to aortic pressures and augmentation index (AIx) were analyzed in 398 patients (mean age, 56 years) with ED but without established cardiovascular (CV) disease. RESULTS: During the mean follow-up period of 6.5 years, a total of 29 (6.5%) MACEs occurred. The adjusted relative risk of MACEs was 1.062 (95% confidence interval (CI), 1.016-1.116) for a 10-mm Hg increase of aortic systolic pressure, 1.119 (95% CI, 1.036-1.155) for a 10-mm Hg increase of aortic pulse pressure (PP), and 1.191 (95% CI, 1.056-1.372) for a 10% absolute increase of AIx. While aortic pressures and AIx did not significantly improve the C-statistic models, the calibration for all indices was satisfactory. Regarding reclassification, the integrated discrimination improvement index (IDI) indicated improvement in risk discrimination of the models that included AIx and aortic PP compared to the reference model in identifying MACEs (IDI = 0.0069; P = 0.024, and IDI = 0.0060; P = 0.036, respectively). The based on categories for 10-year coronary heart disease risk and adapted at 6.5 years overall net reclassification index showed marginal and indicative risk reclassification for AIx (15.7%, P = 0.12) and aortic PP (7.2%, P = 0.20) respectively. CONCLUSIONS: Our results show for the first time that higher central pressures and AIx are associated with increased risk for a MACE in ED patients without known CV disease. Considering the adverse prognostic role of central hemodynamics on outcomes, the present findings may explain part of the increased CV risk associated with ED.