Aortic-brachial stiffness mismatch is a potential new marker of a subclinical vascular damage that has never been studied in patients with rheumatic diseases. The aim of the study was to assess the ...frequency of arterial stiffness mismatch in rheumatoid arthritis (RA) and to evaluate its clinical associations. Materials and Methods. The study group included 85 patients with RA (males 22.4 %, aged 59.7 ± 14.3 years, hypertension in 65 %, mean disease activity score (DAS-28 (C-reactive protein) 3.7 ± 1.1), and the control group included 40 subjects matched by gender, age and risk factors. The study methods included measurements of clinical and ambulatory brachial and aortic blood pressure (BP) (BPLab-Vasotens), arterial stiffness parameters parameters (applanation tonometry, SphygmoCorAtCor), cardio-ankle vascular index (VaSera) and cardio-vascular risk assessments using the SCORE, American College of Cardiology/American Heart Association (ACC/AHA) 2013 pooled cohort equations and QRisk2 scoring systems. The arterial stiffness gradient was calculated as a ratio between carotid-femoral (cf) and carotid-radial (cr) pulse wave velocity, and its elevation of ≥ 1 was considered as arterial stiffness mismatch. A p-value of 0.05 was considered significant. Results and Discussion. The mean stiffness gradient in RA patients without and with hypertension was 1.1 ± 0.1 and 1.4 ± 0.4, respectively (р 0.001); in controls, 0.99 ± 0.2 and 1.3 ± 0.3, respectively (р 0.001). The frequency of stiffness mismatch in the RA group was significantly higher compared to the controls in the whole study population (88.2 % vs 65 % (р = 0.002)) and in both normotensive and hypertensive subgroups (76.7 % vs 43.8 % (p = 0.03), and 94.5 % vs 79.2 % (p = 0.04), respectively). The same trend was observed in the subgroups with normal carotid-femoral pulse wave velocity: arterial stiffness mismatch was present in 82.1 % of RA patients vs. 51.9 % control subjects (p = 0.004). The stiffness gradient was associated with age (r = 0.63), hypertension duration (r = 0.56), cardio-vascular risk by the ACC/AHA 2013 (r = 0.69) and Qrisk2 (r = 0.7) scoring systems, nocturnal aortic systolic BP (r = 0.53), cardio-ankle vascular index (r = 0.60) and diurnal index of brachial systolic BP (r = -0.4). Significant differences in stiffness gradient values were observed in the subgroups based on elevation of aortic systolic BP and pulse wave velocity above individual reference values, aortic pulse pressure 50 mmHg, cardio-ankle vascular index 9, presence of high cardio-vascular risk, masked and nocturnal hypertension, and non-dipping. Conclusion. Patients with RA are characterized by higher frequency of arterial stiffness mismatch compared to controls, irrespective of the history of hypertension or the values of carotid-femoral pulse wave velocity. Arterial stiffness mismatch is associated with unfavorable 24-h BP profile, higher frequency of nocturnal hypertension and cardio-vascular risk.
Aim: The concept of risk age may help overcome an excessive weight of age in cardiovascular risk functions. This study aimed to evaluate the equivalence of risk age with arterial stiffness by ...comparing people with increased risk age and individuals with the same chronological and risk age. In order to materialize this aim, we categorized individuals based on cardiovascular risk and compared groups with increased risk factors (other than age) and groups with normal levels. Methods: This is a cross-sectional population-level study carried out in Girona province within the context of the REGICOR study (Girona Heart Registry). In this study, individuals aged 35-90 years who had a brachial-ankle pulse wave velocity measurement and with no previous cardiovascular disease or peripheral arterial disease were included. Cardiovascular risk was estimated with the FRESCO (in 35-79 year-olds), SCORE2 (in 35-69 year-olds), and SCORE2-OP (in 70-90 year-olds) functions and categorized to calculate and compare (in each category) the median chronological age in the group with increased risk factors and the reference. Arterial stiffness was assessed with the brachial-ankle pulse wave velocity (baPWV). The analyses were carried out separately by sex. Results: In this study, 2499 individuals were included, with a mean age of 59.7 and 46.9% of men. Men presented worse health condition, including a higher mean cardiovascular disease risk score. Both men and women with increased levels of risk factors showed worse health condition than the respective men and women with optimal levels. In each risk category, the groups with higher risk age than chronological age (increased risk factors) were similar in baPWV values to the groups with the same chronological and risk ages (reference), who were consistently older. Conclusions: In categories with the same cardiovascular risk, the arterial stiffness of participants with a higher risk factor burden (increased risk age) matched that of older participants with the rest of the risk factors at optimal levels (same chronological and risk age). These results support the guidelines on the utilization of risk age to explain heightened cardiovascular risk, particularly among individuals in middle age.
Aims: In t he arterial tree, a pressure gradient of the systolic blood pressure (SBP) is observed from the center to the periphery, with the pressure being higher in the periphery because of pressure ...wave reflection. However, this gradient is attenuated, with elevation of the central SBP (cSBP), in cases with abnormal pressure wave reflection in the arterial tree. It remains unclear if increase of the cSBP might be an independent risk factor for accelerated progression of arterial stiffness. We conducted this prospective observational study using latent growth curve model (LGCM) analyses to examine if elevated cSBP might be an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men. Methods: In this 9-year prospective observational study, we analyzed the data of 3862 middle-aged Japanese men (43±10years old) without cerebrocardiovascular disease at the study baseline who had undergone repeated annual measurements of the brachial-ankle pulse wave velocity (baPWV) and cSBP, as represented by the second peak of the radial pressure waveform (SBP2) in radial pressure waveform analysis. Results: During the follow-up period (6.3±2.5years), significant increases of both the baPWV and SBP2 were observed in all the subjects. Analysis using the LGCM confirmed that the SBP2, a marker of the cSBP (B=0.260, P＜0.001), was a significant determinant of the slope of the annual changes of the baPWV during the study period. Conclusions: Our fi nding may appear to confirm elevated cSBP as an independent risk factor for accelerated progression of the arterial stiffness in middle-aged Japanese men.
Aim. To compare the elastic properties of the common carotid arteries (CCA) in patients with stage II hypertension (HTN) depending on the presence of diabetes mellitus (DM) and atherosclerotic plaque ...(ASP) <50 % of carotid arteries (CA). Materials and methods. The study included 80 patients with stage II HTN, 43 of them without type 2 DM, 37 with type 2 DM, average age – 57.7, 55.3 % men. Basic anthropometric data, laboratory indicators of lipid and carbohydrate metabolism, creatinine, data of daily blood pressure monitoring, echocardiography, intima-media thickness, local stiffness indicators: artery diameter, distensibility, the distensibility coefficient (DC), and compliance coefficient (CC), stiffness indices α, β, local pulse wave velocity (PWV), pressure and augmentation index (using radiofrequency-based technologies) were studied. Statistical analysis was performed; the probability of differences is at the level of p < 0.05. Results. The prevalence of ASP in the carotid basin in the group of patients with HTN without DM was 51.1 %, with DM – 54.0 % (p = 0.79). While comparing the elastic properties of CCA of patients without ASP, no reliable similarities were found in the studied indicators. In patients with HTN, accompanying type 2 DM with ASP, the diameter of the CCA was significantly larger by 11.8 % (p = 0.03), and the CC was also higher by 23.6 % (p = 0.049) than in patients with HTN without DM. In patients with HTN with and without DM the limit levels for the intima-media thickness of the left CCA associated with the presence of atheroma were determined, however, the comparison of the areas under the ROC curves did not reveal a statistical difference in the cut-off values in the studied groups (р = 0.681). Conclusions. A feature of CCA remodeling in HTN patients with DM at the stage of ASP presence should be considered a more substantial increase in the diameter of the CCA with preservation of the distensibility of the plaque-free vascular wall. The addition of a second factor (DM) to one risk factor (HTN) is not accompanied by a further statistically significant increase in IMT as a mandatory prerequisite for the appearance of ASP.
Rest-activity rhythm is an essential behavior for human health. However, the association between rest-activity rhythm and atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. ...Therefore, this study aimed to elucidate the association.
This study included 87,039 participants from the UK Biobank who had 7-day accelerometry data and were free of ASCVD at baseline. Relative amplitude was calculated as the difference between the most active continuous 10-h period (M10) and the least active continuous 5-h period (L5) in 24 h, and lower relative amplitude indicated the disruption of rest-activity rhythm. Cox proportional hazard model was used to examine the association of relative amplitude with ASCVD. Further, the linear association between relative amplitude and arterial stiffness measurements, including arterial stiffness index (ASI) and carotid intima-media thickness (cIMT), was examined.
During a mean follow-up period of 6.80 ± 1.10 years, 2798 ASCVD cases were identified. A dose-response relationship was observed between relative amplitude and ASCVD risk (P for trend<0.001). The adjusted hazard ratio, for the highest vs the lowest quintile of relative amplitude, was 1.54 (95 % confidence interval: 1.31, 1.79). Further, we found significant association of lower relative amplitude with ASI and cIMT. The onset timing of M10 at ≤06:00, 09:00, 10:00, or ≥11:00, as opposed to the reference time of 07:00, was associated with higher ASCVD risk.
Low rest-activity rhythm amplitude was associated with a higher risk of ASCVD. Rest-activity rhythm amplitude may provide a method to identify individuals at risk of ASCVD in public health and clinical practice.
•Rest-activity rhythm is an essential behavior for human health.•Low rest-activity rhythm amplitude was associated with higher ASCVD risk.•Early or late onset timing of 10h activity was associated with higher ASCVD risk.•Low rest-activity rhythm amplitude was associated with increased arterial stiffness.•Rest-activity rhythm amplitude could be a novel risk factor for ASCVD.
Abstract
Aims
The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. ...Our aim was to examine whether gut microbial composition is associated with arterial stiffness.
Methods and results
We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= −0.25(0.07), P = 1 × 10−4) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing—two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3–12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure.
Conclusions
Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing.
In 2014, Japan was estimated to have approximately 27 million patients with hypertension (HT), and the ultimate goal of treatment is to prevent complications of HT, including heart failure (HF). The ...major structural changes in the heart that cause HF are left ventricular (LV) hypertrophy (LVH) and the resulting LV diastolic dysfunction. However, in patients with HT with well-controlled blood pressure (BP), whether they are in HF stage A (only HT) or B (with organic heart disease) is often unclear. It has been reported that strict BP control suppresses LVH, and the improvement of LVH leads to the suppression of cardiovascular complications. Thus, detecting HF stage B HT and providing appropriate treatment lead to the suppression of HF onset. This review focuses on the detection and treatment of organic heart disease in HT.
Diabetes may induce multiple organ damage; therefore, early detection of individuals at high-risk of incident diabetes is important for timely risk assessment and intervention. Arterial stiffness ...(AS) occurs as a result of functional and structural changes in the arterial wall. Growing body of evidence suggests that AS is a risk factor for incident diabetes. Although each study could use different indicators for AS (ex cf-PWV, baPWV, etc.), they came to similar conclusion that AS was associated with higher risk of incident diabetes. The underlying mechanisms for the relationship of AS with risk of diabetes remain to be elucidated, but there could be several potential mechanisms. Diabetes and AS are expected to share common risk factors and influence each other, but recent research showed some evidence that AS can directly increase the risk of diabetes. The link between AS and incident diabetes has important clinical implications. First, it suggests that AS might be a useful marker for identifying people at high risk for developing diabetes. Second, it suggests that reducing AS may prevent or delay the onset of diabetes. Early detection and possible slowing of the vascular stiffening process with pharmacological agents and lifestyle interventions may reduce associated risks for diabetes.
Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted ...antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60–79 years) with impaired endothelial function (brachial artery flow–mediated dilation <6%) underwent 6 weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover design study. MitoQ was well tolerated, and plasma MitoQ was higher after the treatment versus placebo period (P<0.05). Brachial artery flow–mediated dilation was 42% higher after MitoQ versus placebo (P<0.05); the improvement was associated with amelioration of mitochondrial reactive oxygen species–related suppression of endothelial function (assessed as the increase in flow-mediated dilation with acute, supratherapeutic MitoQ 160 mg administration; n=9; P<0.05). Aortic stiffness (carotid–femoral pulse wave velocity) was lower after MitoQ versus placebo (P<0.05) in participants with elevated baseline levels (carotid–femoral pulse wave velocity >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo (P<0.05). Participant characteristics, endothelium-independent dilation (sublingual nitroglycerin), and circulating markers of inflammation were not different (all P>0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT02597023.
Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults ...without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structural background for cardiovascular events. The present paper provides a critical overview of the clinical evidence linking diabetes-related metabolic abnormalities to cardiovascular risk, debates the pathophysiologic mechanisms through which insulin resistance and hyperglycemia may affect the arterial wall, and discusses the associations between vascular biomarkers, metabolic abnormalities and cardiovascular events.
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