Search

OBJECTIVE Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype. METHODS A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations. RESULTS PWV and central pulse pressure were significantly higher in MFS patients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86) m/s, P = 0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3) mmHg, P

Background: Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with arterial aging. The aim of our study was to evaluate the relationship between SUA, oxLDL and arterial stiffness in subjects with normal renal function and in patients with mild or moderate renal impairment. Methods: From the database of the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker subjects without cardiovascular disease and with normal renal function (n = 205), subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with stage III CKD (n = 94). All subjects underwent a determination of the LDL oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV). Results: By univariate analysis, PWV correlated with a large number of clinical, haemodynamic and metabolic parameters, including estimated glomerular filtration rate (eGFR) in subjects with normal renal function and in those with stage II or III CKD. Stepwise multiple regression analyses showed that in the presence of normal renal function or stage II CKD, the main predictors of PWV were age, systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while in the presence of stage III CKD only age, SBP and apolipoprotein B remained significant (p < 0.05). Conclusion: Both ox-LDL and SUA independently predicts PWV only in subjects with normal or mildly reduced renal function, but not in the subjects with more compromised eGFR. This study confirms the complex relationship of SUA with cardiovascular and metabolic disease in the patient with established renal disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is associated to increased risk of cardiovascular disease. Our aim was to evaluate association of indexes of fatty liver with arterial stiffness (AS). METHODS: We analyzed data of adult volunteers visited during the last Brisighella survey. We evaluated the Pulse Wave Velocity (PWV) and the following non-invasive indexes of liver steatosis: Fatty Liver Index (FLI), Lipid Accumulation Product (LAP), Hepatic Steatosis Index (HSI). We compared patients according to the risk of Non-Alcoholic Steatohepatitis (NASH): low-risk (BMI

OBJECTIVE: The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects. MATERIALS AND METHODS: We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75 ± 0.53 years. RESULTS: At baseline the mean age was 54.5 ± 12.6 years, SBP and DBP were 141.3 ± 18.6 and 86.4 ± 10.4 mmHg and PWV was 8.56 ± 1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (ΔPWV 0.87 ± 3.05 m/s). PWV and ΔPWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ΔPWV showed a greater increase as compared to patients with controlled BP (1.46 ± 3.67 vs 0.62 ± 2.61 m/s, p

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PWV.

Background Chronic increased arterial blood pressure has been associated with executive dysfunction, slowing of attention and mental processing speed, and later with memory deficits. Due to the absence of a concrete therapeutic approach to this pathophysiological process, in the last decades there has been an increasing interest in the use of nutraceuticals, especially those with antioxidant properties, which own strong neuroprotective potential, that may help to improve cognitive function and to delay the onset of dementia. Results We evaluated the effects of the treatment with a new nutraceutical preparation containing different molecules with potent antioxidant properties (AkP05, IzzeK®) and placebo on a cohort of thirty-six hypertensive patients. At baseline, neuropsychological evaluation, arterial stiffness and biochemical parameters of the subjects were comparable. After 6 months of treatment, there was a significant reduction of the augmentation index in the AkP05-treated group. Moreover, the measurement of cognitive function, evaluated with MoCA test and Word Match Testing, showed a significant improvement in patients receiving the active treatment. In addition, the group treated with nutraceutical reached a better Stroop test score, while subjects that received placebo did not showed any improvement. Finally, a positive relationship between SBP variation and the psychometric assessment with the EQ-VAS scale was observed only in the active treatment group. Conclusions In this study, we demonstrated that the therapy with a new nutraceutical preparation is able to significantly increase the scores of important neuropsychological tests in hypertensive patients already on satisfactory blood pressure control. Although future studies are needed to better characterize the molecular mechanisms involved, these results candidate the new nutraceutical combination as a possible therapeutic strategy to support the cerebrovascular functions and delay the onset of dementia in hypertensive patients.

Background Marfan syndrome is characterized by aortic root dilation, beginning in childhood. Data about aortic pulsatile hemodynamics and stiffness in pediatric age are currently lacking. Methods and Results In 51 young patients with Marfan syndrome (12.0±3.3 years), carotid tonometry was performed for the measurement of central pulse pressure, pulse pressure amplification, and aortic stiffness (carotid‐femoral pulse wave velocity). Patients underwent an echocardiogram at baseline and at 1 year follow‐up and a genetic evaluation. Pathogenetic fibrillin‐1 mutations were classified between “dominant negative” and “haploinsufficient.” The hemodynamic parameters of patients were compared with those of 80 sex, age, blood pressure, and heart‐rate matched controls. Central pulse pressure was significantly higher (38.3±12.3 versus 33.6±7.8 mm Hg; P =0.009), and pulse pressure amplification was significantly reduced in Marfan than controls (17.9±15.3% versus 32.3±17.4%; P P =0.010; β=−0.271, P =0.026). No significant difference in hemodynamic parameters was found according to fibrillin‐1 genotype. Patients who increased aortic Z‐scores at 1‐year follow‐up presented a higher central pulse pressure than the remaining (42.7±14.2 versus 32.3±5.9 mm Hg; P =0.004). Conclusions Central pulse pressure and pulse pressure amplification were impaired in pediatric Marfan syndrome, and associated with aortic root diameters, whereas aortic pulse wave velocity was similar to that of a general pediatric population. An increased central pulse pressure was present among patients whose aortic dilatation worsened at 1‐year follow‐up.

Arterial stiffness is an independent cardiovascular risk factor and sodium intake could be a determinant of arterial stiffness. Nevertheless, the studies that investigated the effect of reducing dietary sodium intake on arterial stiffness in humans provided inconsistent results. Therefore, we performed a systematic review and a meta-analysis of the available randomized controlled trials of salt restriction and arterial stiffness to try and achieve more definitive conclusions. A systematic search of the online databases available (from 1996 through July 2017) was conducted including randomized controlled trials that reported arterial stiffness, expressed by carotid–femoral pulse wave velocity (PWV), as difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Sensitivity, heterogeneity, publication bias, subgroup and meta-regression analyses were performed. Eleven studies met the predefined inclusion criteria and provided 14 cohorts with 431 participants and 1–6 weeks intervention time. In the pooled analysis, an average reduction in sodium intake of 89.3 mmol/day was associated with a 2.84% (95% CI: 0.51–5.08) reduction in PWV. There was no significant heterogeneity among studies and no evidence of publication bias was detected. No single feature of the studies analyzed seemed to impact on the effect of salt restriction on PWV. The results of this meta-analysis indicate that restriction of dietary sodium intake reduces arterial stiffness. This effect seems be at least in part independent of the changes in blood pressure.

Introduction: Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes. Aim: We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables. Methods: In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls. Results: The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P

Introduction: There is conflicting information linking fruit and fructose intake with cardiometabolic disorders. The main objective of our study was to evaluate the association between intake of fruits and sugar-sweetened beverages, and carotid-femoral pulse wave velocity (cfPWV), a non-invasive marker of arterial aging, in a large population sample. Methods: For this study, we selected four age and sex-matched subgroups from the last Brisighella Heart Study population survey, after exclusion of those in secondary prevention for cardiovascular diseases, affected by gout and moderate-to-severe chronic kidney disease (defined as eGFR &lt, 60 mL/min), and/or actively treated with direct vasodilating drugs (calcium-antagonists, alpha-blockers, nitrates). The remaining subjects were classified into four groups: (1) low fruit and low sugar-sweetened beverage intake (LFLB), (2) high fruit and low sugar-sweetened beverage intake (HFLB), (3) low fruit and high sugar-sweetened beverage intake (LFHB), (4) high fruit and high sugar-sweetened beverage intake (HFHB). Results: CfPWV was significantly elevated in subjects consuming a higher fructose load, particularly when it was derived from industrially sweetened beverages (pooled LFHB &amp, HFHB: 9.6 &plusmn, 2.3 m/s, pooled LFLB &amp, HFLB: 8.6 &plusmn, 2.3 m/s, p &lt, 0.001). Moreover, the main predictors of cfPWV values were serum uric acid (B = 0.391, 95%CI 0.321&ndash, 0.486, p = 0.001), fructose load from both fruits and sugar-sweetened beverages (B = 0.310, 95%CI 0.099&ndash, 0.522, p = 0.004), triglycerides (B = 0.228, 95%CI 0.117&ndash, 0.389, p = 0.018), fasting plasma glucose (B = 0.015, 95%CI 0.008&ndash, 0.022, p &lt, 0.001) and estimated Glomerular Filtration Rate (B = &minus, 0.043, 95%CI &minus, 0.052&ndash, &minus, 0.035, p &lt, 0.001). Conclusion: our data suggest that increased intake of fructose derived from industrial sweetened beverages, though not from fruits, is associated with higher pulse wave velocity.

PURPOSE OF REVIEW: The fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may promote cardiometabolic health. This review summarizes the results of recent meta-analyses of prospective studies on cardiovascular diseases, diabetes type 2 and markers of atherosclerosis and thrombosis. RECENT FINDINGS: The results of recently published meta-analyses of prospective cohort studies showed that eating fish once a week was associated with a 16% lower risk of fatal coronary heart disease (CHD) and a 14% lower risk of stroke incidence, but was not related to heart failure. Fish consumption may be associated with a higher risk of diabetes in Western countries and a lower risk in Asian countries. Recent meta-analyses of randomized controlled trials showed that EPA-DHA supplementation reduced the risk of fatal CHD and sudden death by 10% of which the latter was not significant. Extra EPA-DHA did not reduce the risk of heart failure, stroke and cardiac arrhythmias. ¿-3 fatty acid (FA) supplementation did reduce markers of ventricular fibrillation, inflammation and endothelial dysfunction and platelet aggregation. SUMMARY: There is strong evidence for a protective effect of ¿-3 FA on fatal CHD and for some markers of atherosclerosis and thrombosis. Consistent results were not obtained for other vascular diseases and diabetes. ¿-3 FA reduced markers of ventricular fibrillation but did not reduce the risk of atrial fibrillation.

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushing's syndrome. Twenty-four patients with Cushing's syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushing's disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearman's rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified.

Introduction: Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS. Aim: We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI). Methods: 30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated. Results: On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: −42.9 ± 17.2 vs −27.9 ± 10.1, peak: −68.7 ± 29.2 vs −42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup. Conclusions: In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.

Objective: Annexin A5 (AnxA5) has been previously linked to the presence of carotid and cardiac target organ damage (TOD) in the context of heart failure and rheumatologic patients. However, information is scant in the context of hypertension. Aim of our study was to evaluate AnxA5 in treated hypertension patients compared with normotensive controls and to determine whether it is associated with vascular and heart TOD evaluated as arterial stiffness, carotid plaque and left ventricular hypertrophy. Methods: We enrolled 123 consecutive treated hypertension and 124 normotensive controls. TOD was evaluated as pulse wave velocity (PWV, complior), left ventricular hypertrophy (echocardiography) and intima-media thickness and carotid plaque presence (ecographic methods). AnxA5 levels was dosed and compared in patients with and without hypertension and with and without TOD. Results: With similar age hypertension patients showed higher SBP, DBP and AnxA5 levels (13.9 ± 11.1 vs 10.1 ± 8.4 ng/ml, P < 0.001) compared with controls. Regarding TOD hypertension showed higher PWV (8.5 ± 1.8 vs 7.6 ± 1.5 m/s, P < 0.001) and LVMI (121.7 ± 29.3 vs 113.5 ± 21.1 g/m2, P < 0.05), whereas carotid intima-media thickness was superimposable. AnxA5 correlates with PWV (r = 0.13, P < 0.05) and DBP (r = 0.15, P < 0.01), whereas it has never been found as a significant independent predictor of TOD in linear regression analysis. Conclusion: Our data have shown that AnxA5 levels are increased in treated hypertension patients. In this condition, it is probably released in the plasma as a defensive mechanism through its anti-inflammatory and anticoagulants effects. We found a significant association with arterial stiffness, but AnxA5 was not found to be a significant predictor of TOD.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of PCSK 9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants. Methods and Results From the historical cohort of the Brisighella Heart Study, after exclusion of active smokers, participants in secondary prevention for cardiovascular disease, and patients in treatment with statins or vasodilating agents, we selected 227 premenopausal women and 193 age‐matched men and 460 postmenopausal women and 416 age‐matched men. In these participants, we evaluated the correlation between PCSK 9 plasma circulating levels and pulse wave velocity. Postmenopausal women showed higher PCSK 9 levels (309.9±84.1 ng/mL) compared with the other groups ( P P =0.008). In the whole sample, pulse wave velocity was predicted mainly by age (B=0.116, 95% CI 0.96–0.127, P PCSK 9 (B=0.014, 95% CI 0.011–0.016, P CI 0.024–0.391, P =0.026). Physical activity, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, and estimated glomerular filtration rate were not associated with pulse wave velocity ( P >0.05).By considering the subgroups described, age and PCSK 9 levels were mainly associated with pulse wave velocity, which also correlated with serum uric acid in postmenopausal women. Conclusions In the Brisighella Heart Study cohort, circulating PCSK 9 is significantly related to arterial stiffness, independent of sex and menopausal status in women.

Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases.Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment.SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate.Based on our data, SUA seems to be associated with an inadequate BP control in subjects treated with antihypertensive drugs, and subjects with both uncontrolled BP and relatively high SUA levels have also an increased arterial stiffness that (per se) could be a cause of worse BP control under treatment.

The capacity of HDL to induce cell cholesterol efflux is considered one of its main antiatherogenic properties. Little is known about the impact of such HDL function on vascular physiology. We investigated the relationship between ABCA1-dependent serum cholesterol efflux capacity (CEC), an HDL functionality indicator, and pulse wave velocity (PWV), an indicator of arterial stiffness. Serum of 167 healthy subjects was used to conduct CEC measurement, and carotid-femoral PWV was measured with a high-fidelity tonometer. J774 macrophages, labeled with [(3)H]cholesterol and stimulated to express ABCA1, were exposed to sera; the difference between cholesterol efflux from stimulated and unstimulated cells provided specific ABCA1-mediated CEC. PWV is inversely correlated with ABCA1-dependent CEC (r = -0.183; P = 0.018). Moreover, controlling for age, sex, body mass index, mean arterial pressure, serum LDL, HDL-cholesterol, and fasting plasma glucose, PWV displays a significant negative regression on ABCA1-dependent CEC (β = -0.204; 95% confidence interval, -0.371 to -0.037). The finding that ABCA1-dependent CEC, but not serum HDL cholesterol level (r = -0.002; P = 0.985), is a significant predictor of PWV in healthy subjects points to the relevance of HDL function in vascular physiology and arterial stiffness prevention.

Objective. Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid–femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects. Design. The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing. Results. Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640. Conclusions. These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p

Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45years old (median age 31.6±8.1years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx).Total cholesterol (P0.013) and LDL-cholesterol (P0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P0.006 and P0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis.Young IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.

Background: Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management. Objective: We recently launched an investigator-initiated, international, multicenter, observational, prospective study, the Vascular health Assessment Of The Hypertensive patients (VASOTENS) Registry, aimed at (1) evaluating non-invasive 24-hour ABP and arterial stiffness estimates (through 24-hour pulse wave analysis, PWA) in hypertensive subjects undergoing ambulatory blood pressure monitoring (ABPM) for clinical reasons; (2) assessing the changes in estimates following treatment; (3) weighing the impact of 24-hour PWA on target organ damage and cardiovascular prognosis; (4) assessing the relationship between arterial stiffness, BP absolute mean level and variability, and prognosis; and (5) validating the use of a 24-hour PWA electronic health (e-health) solution for hypertension screening. Methods: Approximately 2000 subjects, referred to 20 hypertension clinics for routine diagnostic evaluation and follow-up of hypertension of any severity or stage, will be recruited. Data collection will include ABPM, performed with a device allowing simultaneous non-invasive assessment of 24-hour CAP and arterial stiffness (BPLab), and clinical data (including cardiovascular outcomes). As recommended by current guidelines, each patient will be followed-up with visits occurring at regular intervals (ideally every 6 months, and not less than once a year depending on disease severity). A Web-based telemedicine platform (THOLOMEUS) will be used for data collection. The use of the telemedicine system will allow standardized and centralized data collection, data validation by experts and counseling to remote centers, setup and maintenance of the Registry, and prompt data analysis. Results: First follow-up results are expected to be available in the next 2 years. Conclusions: The results of the VASOTENS Registry will help define the normalcy thresholds for current and future indices derived from 24-hour PWA, according to outcome data, and will also provide supporting evidence for the inclusion of this type of evaluation in hypertension management. Trial registration: Clinicaltrials.gov NCT02577835; https://clinicaltrials.gov/ct2/show/NCT02577835 (Archived by WebCite at http://www.Webcitation.org/6hzZBKY2Q) [JMIR Res Protoc 2016;5(2):e137]

none 8 no Aim:Proprotein convertase subtilisin kexin type 9 (PCKS9) circulating levels are significantly associated with increased risk of total cardiovas-cular events. Risk markers for cardiovascular diseases (CVD) include pa-rameters relative to arterial structure and function. Our study aimed toevaluate the relationship between circulating levels of PCSK9 and arterial stiffness in a large sample of overall healthy subjects.Methods:From the historical cohort of the Brisighella Heart Study, four subgroups were selected; pre-menopausal women (n¼227), age-matchedmen (n¼193), post-menopausal women (n¼460) and age-matched men(n¼416). In these subjects, the correlation between PCSK9 plasma circulating levels and the pulse wave velocity (PWV) was evaluated. Active smokers, participants in secondary prevention for CVD treated with statins or vasodilating agents, were excluded from the analysis.Results:Post-menopausal women showed higher PCSK9 levels (309.9±84.1 ng/mL) compared to he other groups of subjects (p0.05). Considering the above describedsubgroups, age and PCSK9 resulted the main factors associated to PWV; thelatter correlates to serum uric acid only in post-menopausal women.Conclusions:In the Brisighella Heart Study cohort, circulating PCSK9 aresignificantly related to the arterial stiffness, independently from gender and menopausal status. none Cicero, Arrigo; Ruscica, Massimiliano; Ferri, Nicola; Fogacci, Federica; Magni, Paolo; Giovannini, Marina; D'Addato, Sergio; Borghi, Claudio Cicero, Arrigo; Ruscica, Massimiliano; Ferri, Nicola; Fogacci, Federica; Magni, Paolo; Giovannini, Marina; D'Addato, Sergio; Borghi, Claudio

Aims Relationship between obesity and cardiovascular (CV) disease depends not only on the amount of body fat, but also on its distribution. For example, individuals with increased fat accumulation in the abdominal region have atherogenic lipid profiles and are at increased CV risk. The loss of elasticity in medium and large arteries is an early manifestation of atherosclerosis. The aim of this study was to evaluate whether echocardiographic epicardial adipose tissue, an index of cardiac adiposity, is related to carotid stiffness and carotid intima-media thickness (IMT), indexes of subclinical atherosclerosis, better than waist circumference in hypertensive patients.Methods and results We studied 459 patients with Grade I and II essential hypertension who were referred to our outpatient clinic over a period from May 2007 to March 2008. The population was first sorted by waist circumference and then by epicardial fat ≤7 or >7 mm. We measured epicardial fat thickness, waist circumference, carotid artery stiffness, and carotid IMT in all patients. Patients divided according to waist circumference showed no statistical differences in carotid artery stiffness between the two groups. Subjects with epicardial fat >7 mm were older, had higher systolic, diastolic, and pulse pressure, increased left ventricular mass index, carotid IMT, diastolic parameters, and stiffness parameters compared with those with epicardial fat ≤7 mm (P < 0.001). A positive correlation was found between epicardial fat and age, pulse pressure, stiffness parameters, carotid IMT, systolic blood pressure, and duration of hypertension, and a negative correlation was found with diastolic parameters. Age, carotid IMT, and stiffness parameters were independently related to epicardial fat.Conclusion Our findings indicate that epicardial fat reflects carotid artery stiffness in hypertension-induced organ damage. © The Author 2009.

Background Insulin resistance (IR), constitutes an important cardiovascular risk factor and can cause ischemic heart disease. It can lead to left ventricular dysfunction with a mechanism independent of ischemic heart disease and it is closely associated with impaired vascular function. The aim of our study was to explore the impact of IR on cardiac and vascular function, in patients with cardiovascular risk factors but angiographically undamaged coronary arteries. Methods We studied 32 patients (62.06 ± 11.19 years) with cardiovascular risk factors. All patients underwent coronary angiography, echocardiography, Doppler ultrasound of carotid arteries and laboratory tests. Exclusion criteria were coronary artery disease detected by coronary angiography, diabetes mellitus, creatinine above 1.5 mg/dl, atrial fibrillation or malignant arrhythmias, left-ventricular hypertrophy, valvular heart disease, ejection fraction below 50%. The presence of insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Each patient underwent a complete echocardiographic examination including Global Longitudinal Strain assessment and carotid artery ultrasound scan including measurement of arterial stiffness. Results The patients were divided into two groups based on the median value of HOMA-IR, the first group for values

Background: Heart failure with reduced ejection fraction (HFrEF) is characterized by activation of the sympathetic nervous system and increased arterial stiffness, leading to an impaired ventricular-vascular coupling. Baroreflex activation therapy (BAT) has been shown to reduce muscle sympathetic nerve activity (MSNA) and improve clinical status of patients with HFrEF. The purpose of this investigation was to determine the effects of BAT on arterial stiffness in HFrEF. Methods and results: MSNA, clinical variables, and parameters of central blood pressure (BP) and arterial stiffness were collected in 18 NYHA Class III HFrEF patients, nine receiving BAT and nine continuing with optimal medical management alone. Patients were followed for 3 months, with measurements at that time compared to baseline evaluation. Baseline characteristics of the groups were well matched. At 3 months, BAT did not improve central BP and arterial stiffness despite a significant amelioration of MSNA, NYHA class, Minnesota living with heart failure questionnaire score, number of heart failure medications and six-minute walking distance. The control group exhibited no significant changes in all the measured variables. Conclusions: Despite significant reductions in MSNA and clinical improvement, BAT does not appear to chronically modify arterial stiffness within this HFrEF cohort. Additional study is required to determine if this result applies to the HFrEF population as a whole.

Background/objectives: Several studies reported an increased cardiovascular (CV) morbidity and mortality in patients with primary aldosteronism (PA). We performed a meta-analysis on the impact of PA on major markers of CV risk. Methods: Studies on the relationship between PA and common carotid artery intima-media thickness (CCA-IMT), prevalence of carotid plaques, flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), pulse-wave velocity (PWV), augmentation index (AIx), and ankle-brachial index (ABI) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: 12 case-control studies (445 cases, 472 controls) were included. Compared to subjects with essential hypertension (EH), PA patients showed a higher CCA-IMT (MD: 0.12 mm; 95% CI: 0.09, 0.16; P

Background: Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with uncontrolled hypertension. The exact mechanisms by which RDN results in BP reductions are yet not fully established. Methods and results: This study investigated the effects of RDN on office BP, 24-h ambulatory BP, noninvasive 10-min beat-to-beat digital pulse wave analysis, total peripheral resistance (TPR), cardiac output, and plasma renin and aldosterone serum concentrations in 30 patients with resistant hypertension. Adherence to antihypertensive drugs was assessed by liquid chromatography highresolution tandem mass spectrometry analysis in plasma and urine at baseline and at 6 month. RDN significantly reduced office BP, beat-to-beat BP, and 24-h ambulatory BP by 19/6 (P=0.021/P=0.012), 12/7 (P=0.005/ P=0.005), and 10/5mmHg (P=0.001/P=0.049) at 6 months, respectively. TPR decreased from 1696 to 1377 dyn s/cm5 (19%; P=0.027). This reduction was not associated with significant changes in cardiac output. The changes in office, ambulatory, and beat-to-beat BP correlated with the reductions of TPR. Adherence to antihypertensive treatment remained unchanged during the study period (84.7% at baseline, 83.6% at 6 months, P=0.782). Conclusion: RDN reduced office BP, beat-to-beat BP, and 24-h ambulatory BP in patients with resistant hypertension after 6 months. The BP changes were associated with reductions in peripheral resistance, whereas cardiac output, plasma renin, and aldosterone levels remained unchanged. The observed effects were not explained by an increased intake of antihypertensive medications.

BACKGROUND Structural atherosclerotic damage, arterial stiffness, pulse pressure (PP), and renal hemodynamics may interact and influence each other. Renal resistance index (RRI) appears as a good indicator of systemic vascular changes. The aim of our study was to assess the independent relationships of carotid intima-media thickness (cIMT), aortic pulse wave velocity (aPWV), and peripheral PP with RRI in hypertensives with various degrees of renal function. METHODS We enrolled 463 hypertensive patients (30-70 years) with normal renal function (group 0; n = 280) and with chronic kidney disease (groups I-V; n = 183). All subjects underwent ultrasonographic examination of intrarenal and carotid vasculature, as well as a 24-h ambulatory blood pressure monitoring. RESULTS A statistically significant difference in RRI, cIMT, aPWV, and clinic PP was observed in the different 6 groups (all P < 0.001), even after adjustment for age. RRI correlated with cIMT (r = 0.460, P < 0.001), aPWV (r = 0.386, P < 0.001), clinic PP (r = 0.279, P < 0.001), and 24-h PP (r = 0.229, P < 0.001) in the entire study population. These correlations were similar in subjects with and without renal dysfunction. In the overall study population, the association between RRI, cIMT, and clinic PP remained statistically significant even after adjustment for various confounding factors, whereas the relationship between RRI and aPWV was lost in multivariate analysis. CONCLUSIONS cIMT and clinic PP rather than directly aPWV are associated with intrarenal hemodynamics. Our results confirm that in hypertensives RRI not only detects derangement of intrarenal circulation but may also be considered as a sensor of systemic vascular changes, independently of level of renal function.

Study Objectives: Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) have been associated with increased risk of cardiovascular disease (CVD). OSA has also been linked to increased large arterial stiffness, which is considered an independent risk factor for CVD. We utilized a previously validated index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) to seek comparison in patients with PLMS and OSA. Methods: Forty-nine adult male subjects, without known comorbidities that could affect arterial stiffness or on vasoactive medication, were retrospectively identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17), and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index (PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h. SIDVP was derived from the raw data of photoplethysmography of the nocturnal polysomnography, averaged for 2 min prior to sleep study initiation (baseline), after completion in the morning, and every half hour after sleep onset. Results: The groups were age/body mass index-matched. Controls showed lower baseline, morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with PLMS (PLMI: 50.69 ± 9.7 events/h) and the OSA group (AHI: 29.7 ± 2 events/h) demonstrated similar overall SIDVP (6.78 ± 0.08 versus 6.94 ± 0.04, respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 ± 8, PLMI: 50.63 ± 7.2) group demonstrated the highest (7.40 ± 0.06, p < 0.001). Conclusions: Based on an easily reproducible and applicable marker of large arterial stiffness, patients with significant PLMS had higher SIDVP when compared to controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had the highest SIDVP, implying a possible additive effect of OSA and PLMS on arterial stiffness.

In rats, an increase in heart rate by pacing is accompanied by progressive large-artery stiffening. Whether this is also the case in humans is unknown. We enrolled 20 patients who were chronically implanted with a pacemaker because of atrioventricular block or sick sinus syndrome. Arterial distensibility was measured by an echo-tracking device. In 10 patients, the evaluation was performed on the radial artery by using continuous finger blood pressure measurements, whereas in the remaining 10 patients, the common carotid artery was studied with a semiautomatic measure of brachial artery blood pressure. Diastolic diameter, systodiastolic diameter change, and distensibility were obtained at baseline (heart rate 63±2 beats/min) and after atrial and ventricular sequential pacing at a heart rate of 90 and 110 beats/min. At baseline, the diameter was 7.8±0.3 mm in the carotid artery and 2.4±0.1 mm in the radial artery; the respective systodiastolic diameter change values were 375.4±31.0 and 55.9±9.0 (μm) and the distensibility values were 1.4±0.1 and 0.7±0.1 (1/mm Hg 10 −3 ). Blood pressure and diameter were not significantly modified by increasing heart rate, which markedly modified systodiastolic diameter change and distensibility. In the radial artery, distensibility was reduced by 47% ( P P P

BACKGROUND In the last 2 decades, new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. The aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. METHODS Twenty-nine patients (27 affected by renal and 2 by thyroid cancer), received treatment with anti-VEGFR drugs. Brachial blood pressure (BP), central BP, carotid-femoral pulse wave velocity (cfPWV), augmentation index (Aix), and several echocardiographic markers of systolic and diastolic left ventricular functions including global longitudinal strain were measured before starting treatment (T0), after 2 (T1), and 6 weeks (T2) of treatment. RESULTS Anti-VEGFR treatment was accompanied by a significant increase of both peripheral (systolic BP +13±15.5mm Hg, diastolic BP +7.1±9.3mm Hg, P < 0.001) and central BP (systolic BP +14±14.2mm Hg, diastolic BP +7.3±10.4mm Hg, P < 0.001) and a significant raise of cfPWV (+1.3±1.8 m/sec, P = 0.003). There was also a significant alteration of markers of diastolic and subclinical left ventricular systolic function, including global longitudinal strain (-19.9±3.8% at T0, -17.8±2.6% at T2, P < 0.05). All the changes were already evident at T1, worsened at T2 in patients who maintained oncological treatment, but disappeared at T2 in patients in whom treatment was stopped. CONCLUSIONS All the changes regarding BP and cfPWV appear early after treatment initiation and seem to be reversible if treatment is stopped, instead diastolic and systolic left ventricular function are persistently altered by anti-VEGFR drugs.

Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca’ Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p

HIV infected subjects present an unfavorable cardiovascular (CV) risk profile that is determined by the infection itself, highly active anti-retroviral therapy (HAART) and other factors, such as chronic kidney disease (CKD). Information is scant and contradictory on whether these factors are associated with arterial stiffness and blood pressure (BP) alteration. Our study aimed to evaluate those parameters in HIV-positive subjects both with and without HAART and with and without CKD, which was defined as the presence of microalbuminuria with a normal glomerular filtration rate. We enrolled 94 HIV-infected subjects without known CV risk factors and compared them with 37 control subjects. We recorded brachial and central BP (pulse wave analysis) and pulse wave velocity ( SphygmoCor). HIV-positive subjects of similar ages and with similar BP values showed central pulse pressure values that were significantly greater than those of controls; this was also the case for the Aix value. Central systolic and pulse pressure values and Aix were significantly greater in HIV-positive subjects with HAART and CKD than in the other HIV-positive subgroups and control subjects. PWV was also superimposable between groups when the data were analyzed relative to the presence of HAART and CKD. Our study shows that the unfavorable CV risk profile associated with HIV infection includes an increase in both central BP and Aix. The central BP increase seems to be favored by renal damage, which apparently has a role in the early stages of the disease.

Objective: Cardiovascular risk factors are widely reputed to be a possible cause for hearing impairment, and the role of arterial stiffness as a cardiovascular risk predictor has been recently emphasized. For these reasons pulse wave velocity (PWV) could represent a useful parameter in order to rapidly assess or rule out the existence of an underlying overall deteriorating circulatory condition in cases of inner ear impairment.Method: In order to assess the real significance of PWV for audiological purposes, a study was carried out comparing this parameter in subjects with normal hearing and those with symmetrical sensorineural hearing loss.Results: The results suggested an apparent lack of correlation between arterial stiffness and hearing deterioration.Conclusion: The findings appear to indicate that the relationship between systemic circulation and inner ear function, when excluding acute and/or well identifiable impairment factors, is not as linear as expected.

BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, e-GFR-EPI, HOMA, quantitative HCV-RNA. RESULTS. HCV(+) patients with respect to NT had an increased pulse wave velocity (7.9 ± 2.1 vs 6.4 ± 2.1 m/s; P < 0.0001), similar to that observed in HT group (8.8 ± 3.2 m/s). HCV(+) patients, in comparison with NT, had higher triglyceride, creatinine, fasting insulin and HOMA (3.2 ± 1.3 vs 2.5 ± 1.0; P < 0.0001). At linear regression analysis, the correlation between pulse wave velocity and HOMA was similar in HT (r = 0.380, P < 0.0001) and HCV(+) (r = 0.369, P = 0.004) groups. At multiple regression analysis, HOMA resulted the major determinant of pulse wave velocity in all groups, explaining respectively 11.8%, 14.4% and 13.6% of its variation in NT, HT and HCV(+). At correlational analysis hepatitis C virus-RNA and HOMA demonstrated a strong and linear relationship between them, explaining the 72.4% of their variation (P = 0.022). CONCLUSIONS. We demonstrated a significant and direct correlation between HOMA and pulse wave velocity in HCV(+) patients, similar to that observed in hypertensives.

Baroreflex sensitivity (BRS) and central arterial function are significantly worsened after menopausal transition. This study tested the hypothesis that administration of n-3 polyunsaturated fatty acids (n-3 PUFA) might contribute to prevent these adverse changes in the vascular function of ovariectomized rats, an animal model of experimental menopause.We randomized 30 female Wistar rats, 2months old, into 3 groups: control (CTRL), sham surgery, normal diet; ovariectomized with normal diet (OVX) and ovariectomized with n-3 PUFA supplementation by daily gavage (0.8g/kg/d) (OVX+O3). Two months after surgery, BRS was calculated as the bradycardic response to phenylephrine-induced blood pressure increase, while large artery function was estimated by the graphical analysis of the aortic pressure wave (diastolic to systolic pressure-time integral ratio, DTI/STI).Ovariectomy caused a significant decrease in BRS (CTRL: 6.23±0.68ms/mmHg; OVX: 2.85±0.75; p0.001). n-3 PUFA supplementation prevented part of the decline of BRS caused by surgical menopause (OVX+O3: 4.75±0.53; p0.01 vs OVX). In animals treated with n-3 PUFA, the central arterial pressure profile did not show the changes in DTI/STI ratio seen in OVX (OVX: 3.31±1.72; OVX+O3: 3.83±1.52; p0.01).In an experimental model of menopause, treatment with n-3 PUFA normalized central hemodynamics and prevented the decrease in BRS, associated with the reduction of compliance of the arterial wall. These findings suggest a therapeutic benefit of n-3 PUFA supplementation in the prevention of postmenopausal vascular disease.