The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.

NETosis in Acute Thrombotic Disorders.

The release of extracellular traps by neutrophils (NETs) represents a novel active mechanism of cell death that has been recently implicated in the pathogenesis of thrombotic disorders. The aim of this study was to investigate the generation of NETs in different groups of patients with acute thrombotic events (ATEs) and to establish whether NETs markers can predict the risk of new cardiovascular events. We performed a case-control study of patients with ATE, including acute coronary syndrome (n = 60), cerebrovascular accident (n = 50), and venous thromboembolism (n = 55). Control subjects (n = 70) were identified among patients admitted for acute chest pain and in which a diagnosis of ATE was excluded. Serum levels of NET markers and neutrophil activation, such as myeloperoxidase (MPO)-DNA complexes, neutrophil gelatinase-associated lipocalin, polymorphonuclear neutrophil elastase, lactoferrin, and MPO, were measured in each patient. We found that circulating levels of MPO-DNA complexes were significantly increased in patients with ATE (p < 0.001) compared with controls and that this association remained significant even after fully adjustment for traditional risk factors (p = 0.001). A receiver operating characteristics analysis of circulating MPO-DNA complexes in discriminating between controls and patients with ATE showed a significant area under the curve of 0.76 (95% confidence interval: 0.69-0.82). After a median follow-up of 40.7 (± 13.8) months, 24 out of the 165 patients with ATE presented a new cardiovascular event and 18 patients died. None of the markers under investigation influenced survival or the incidence of new cardiovascular events. In conclusion, we found that increase of markers of NETosis can be observed in acute thrombotic conditions, occurring both on the arterial and venous site. Nevertheless, the level of neutrophil markers measured during the ATE is not predictive of future risk of mortality and cardiovascular events.

Biomarkers of Neutrophil Activation in Patients with Symptomatic Chronic Peripheral Artery Disease Predict Worse Cardiovascular Outcome.

Neutrophils play a role in cardiovascular (CV) disease. However, relatively scant evidence exists in the setting of peripheral artery disease (PAD). The aims of this study were to measure biomarkers of neutrophil activation in patients with symptomatic chronic PAD compared with healthy controls, to assess their association with PAD severity, and to evaluate their prognostic value in patients with PAD. The following circulating markers of neutrophil degranulation were tested: polymorphonuclear neutrophil (PMN) elastase, neutrophil gelatinase-associated lipocalin (NGAL), and myeloperoxidase (MPO). Neutrophil extracellular traps (NETs) were quantified by measuring circulating MPO-DNA complexes. Patients with PAD underwent a comprehensive series of vascular tests. The occurrence of 6-month major adverse CV (MACE) and limb events (MALE) was assessed. Overall, 110 participants were included, 66 of which had PAD. After adjustment for conventional CV risk factors, PMN-elastase (adjusted odds ratio [OR]: 1.008; 95% confidence interval [CI]: 1.002-1.015; p = 0.006), NGAL (adjusted OR: 1.045; 95%CI: 1.024-1.066; p < 0.001), and MPO (adjusted OR: 1.013; 95%CI: 1.001-1.024; p = 0.028) were significantly associated with PAD presence. PMN-elastase (adjusted hazard ratio [HR]: 1.010; 95%CI: 1.000-1.020; p = 0.040) and MPO (adjusted HR: 1.027; 95%CI: 1.004-1.051; p = 0.019) were predictive of 6-month MACE and/or MALE. MPO displayed fair prognostic performance on receiver operating characteristic (ROC) curve analyses, with an area under the curve (AUC) of 0.74 (95%CI: 0.56-0.91) and a sensitivity and specificity of 0.80 and 0.65, respectively, for a cut-off of 108.37 ng/mL. MPO-DNA showed a weak inverse correlation with transcutaneous oximetry (TcPO2) on proximal foot (adjusted ρ -0.287; p = 0.032). In conclusion, in patients with symptomatic chronic PAD, enhanced neutrophil activity may be associated with an increased risk of acute CV events, rather than correlate with disease severity. Further research is needed to clarify the role of neutrophils in PAD natural history.

The contribution of bio-psycho-social dimensions on sexual satisfaction in people with spinal cord injury and their partners: an explorative study.

STUDY DESIGN: Cross-sectional explorative observational study. TITLE: Sexual satisfaction in people with spinal cord injury and their partners: an explorative study. OBJECTIVE: To investigate the determinants of sexual satisfaction among individuals with spinal cord injury and relative partners by assuming a bio-psycho-social perspective. SETTING: Online survey. METHODS: Thirty-eight individuals (22 individuals with SCI and their partners) were provided with an anonymous self-report questionnaire. Bio-psycho-social dimensions were investigated by using the Barthel Modified Index, Beck Depression Inventory-II, Short Form Health Survey (SF-36). Sexual attitudes of participants were assessed via the Multidimensional Sexual Self-Concept Questionnaire (Snell, 1993). RESULTS: While no differences were observed between individuals with SCI and their partners, women with SCI were overall more satisfied about their sexual life when compared to men with SCI. Coping strategies promoting self-efficacy and an active role in the sexual issues were predictive of Sexual Satisfaction in the couples of persons with SCI and their partners. No significant contribution was played by physical variables. CONCLUSION: A tailored-made approach assessing the needs of both individuals with SCI and partners is a key aspect for effective sexual rehabilitation protocols. According to the needs and features of each couple, health professionals should drive individuals with SCI and partners to cope with their sexuality within a bio-psycho-social framework underlying it.

Differences between males and females with spinal cord injury in the experience of subliminal and explicit sexual pictures.

STUDY DESIGN: Observational cross-sectional study. OBJECTIVES: To determine the differences between persons with spinal cord injury (SCI) and control individuals in terms of conscious and unconscious sexual responses to subliminally presented visual sexual stimuli. SETTING: Spinal cord injury rehabilitation center in northern Italy. METHODS: A two-part behavioral experiment was conducted on 40 participants (27 individuals with SCI; 13 controls). In first part, all participants were subliminally exposed to a prime picture (neutral or sexual) and asked to rate the extent to which they were emotionally aroused, while watching a set of explicit target pictures (neutral or sexual). In the second part, choice reaction time task was employed, wherein participants were shown a subliminal prime picture (neutral or sexual) followed by an explicit target picture (neutral or sexual) superimposed by a black dot and were asked to locate the dot as fast as possible. RESULTS: In the first part, men with SCI reported higher levels of emotional arousal to explicit sexual target pictures compared to other groups. In the second part, slower choice reaction times were found in the SCI group, particularly with sexual prime picture. Moreover, females with SCI spent more time during implicit motor learning tasks with sexual target pictures than other groups. CONCLUSION: We found differences in the experience of subliminal and explicit sexual pictures not only between the two groups, but also between females and males with SCI. Attention should thus be paid when considering sexual experience at subliminal and conscious level in SCI population for future research and rehabilitative protocols.

Lipid Profile and Vascular Remodelling in Young Dyslipidemic Subjects Treated with Nutraceuticals Derived from Red Yeast Rice.

BACKGROUND AND AIMS: A relevant role is emerging for functional foods in cardiovascular prevention. The aim of this study was to assess the effect of a nutraceutical multitargeted approach on lipid profile and inflammatory markers along with vascular remodelling in a cohort of dyslipidemic subjects without history of cardiovascular (CV) disease. METHODS AND RESULTS: We enrolled 25 subjects (mean age 48.2 years) with low to moderate CV risk profile and total cholesterol (TC) levels between 150 and 250 mg/dl. The patients were assigned to receive for one year a tablet/die of a nutraceutical combination containing red yeast rice (RYR) extract (Monacolin 3 mg/tablet) and coenzyme Q10 (30 mg/tablet). Treatment with the nutraceutical compounds led to a significant reduction of TC (from 227 to 201 mg/dl, p < 0.001), LDL-c (from 150 to 130 mg/dl, p = 0.001), triglycerides (from 121 to 109 mg/dl, p = 0.013), non-HDL-cholesterol (from 168 to 141 mg/dl, p < 0.001), hs-CRP (from 1.74 to 1.20 mg/l, p = 0.015), and osteoprotegerin (from 1488 to 1328 pg/ml, p = 0.045). Levels of HDL-c, Lp(a), glucose, liver enzyme, CPK, or creatinine did not change over time. An ultrasound study was performed to assess changes in mean carotid intima-media thickness (IMT) and maximum IMT (M-MAX) as well as modification in local carotid stiffness by means of determining the carotid compliance coefficient (CC) and distensibility coefficient (DC). At the end of the treatment, we observed small but significant reductions in both mean-IMT (from 0.62 to 0.57 mm, p = 0.022) and M-MAX (from 0.79 to 0.73 mm, p = 0.002), and an improvement in carotid elasticity (DC from 22.4 to 24.3 × 10-3/kPa, p = 0.006 and CC from 0.77 to 0.85 mm2/kPa, p = 0.019). CONCLUSIONS: A long-term treatment with a combination of RYR and coenzyme Q10 showed lipid-lowering activity along with a reduction of inflammatory mediators and an improvement of vascular properties in young subjects with a low-to-moderate CV risk profile.

Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study.

OBJECTIVE: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. METHODS: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ±â€Š66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. RESULTS: Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ±â€Š15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ±â€Š24.6 and 85.2 ±â€Š13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. CONCLUSION: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.

Developing an instrument for an early prediction model of long-term functional outcomes in people with acquired injuries of the central nervous system: protocol and methodological aspects.

Severe acquired brain injury (ABI) is a major cause of long-term disability and is the main determinant of health and societal costs. Early identification of favourable long-term recovery would allow personalized rehabilitative programs and better health care resources allocation. In light of the higher survival rate from intensive care units (ICU) in recent years, there is a growing need for early prognostication markers of functional recovery; to date, these data have been mainly collected at rehabilitation unit admission and not during the acute phase. We present the protocol and methodology to develop prediction models in people with severe acquired brain injury (GCS at admission to ICU < 8) for the functional and cognitive outcome at 12 months from the event. Predictors will be collected during the acute stage. Participants will be recruited within the first 72 h from the event in the ICUs of two teaching hospitals (Padova and Treviso). Participants will be followed up at discharge from ICU, admission and discharge from Neurorehabilitation and after 12 months from the event. Clinical and functional scales, electroencephalography, evoked potentials, magnetic resonance imaging and serological markers will be entered into a digital registry. Survival will be estimated using the Cox proportional hazard model. A multivariate prediction model will be developed for each of the functional and cognitive outcomes at 12 months from the event.

Serum uric acid levels and the risk of recurrent venous thromboembolism.

Essentials Increase in serum uric acid (SUA) levels has been widely associated with higher risk of cardiovascular disease. We investigated the link between SUA levels and the risk of venous thromboembolism (VTE) recurrence. Patients with SUA levels ≥ 4.38 mg/dL showed a three-fold increase in the risk of VTE recurrence. Elevated SUA levels are associated with increased risk of recurrent VTE independently from traditional risk factors. ABSTRACT: Background The link between serum uric acid (SUA) and the risk of cardiovascular disease is well established. However, the impact of SUA levels on the risk of venous thromboembolism (VTE) recurrence is unknown. Objectives To investigate the association between SUA and the risk of VTE recurrence. Patients and Methods We performed a monocenter, prospective study on 280 patients with a previous episode of VTE that completed the oral anticoagulant period. SUA levels at enrollment were correlated with the risk of VTE recurrence (mean follow-up 71.1 ± 29.2 months). Results Patients were stratified according to SUA tertiles distribution at baseline (tertiles cut-off: I ≤ 4.37 mg/dL, II 4.38--5.54 mg/dL, III ≥ 5.55 mg/dL). Fifty episodes of VTE recurrence occurred during the follow-up and Kaplan-Meier survival analysis showed that subjects in the lower tertile of SUA distribution had significantly lower risk of future VTE recurrence (P = .003). No differences were seen among patients belonging to the second and the third tertile of SUA distribution. A multivariate Cox regression analysis showed that higher tertiles of SUA distribution had about three-fold increase in the risk of VTE recurrence as compared to subjects with SUA ≤ 4.37, independently from potential confounders (hazard ratio [HR] 3.04, 95% confidence interval [CI] 1.15--8.05 P = .025). Moreover, we observed that the adjusted hazard of VTE recurrence increased by 30% for each additional unit of SUA (mg/dL; HR 1.30, 95% CI 1.01--1.22, P = .040). Conclusion Elevated SUA levels are associated with increased risk of future VTE recurrence independently from traditional risk factors.

Use of RAAS Inhibitors and Risk of Clinical Deterioration in COVID-19: Results From an Italian Cohort of 133 Hypertensives.

BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients. METHODS: A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09-0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17-1.83, P = 0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.

l-Arginine prevents inflammatory and pro-calcific differentiation of interstitial aortic valve cells.

BACKGROUND AND AIMS: Reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of calcific aortic stenosis. Herein, we investigated the effects of l-Arginine, the main precursor of NO, on the osteogenic differentiation of aortic interstitial valve cells (VICs). METHODS: We isolated a clonal population of bovine VICs that expresses osteogenic markers and induces calcification of collagen matrix after stimulation with endotoxin (LPS 500 ng/mL). VICs were treated in vitro with different combinations of LPS ± l-Arginine (50 or 100 mM) and cell extracts were collected to perform proteomic (iTRAQ) and gene expression (RT-PCR) analysis. RESULTS: l-Arginine prevents the over-expression of alkaline phosphatase (ALP, p < 0.001) and reduces matrix calcification (p < 0.05) in VICs treated with LPS. l-Arginine also reduces the over-expression of inflammatory molecules induced by LPS (TNF-alpha, IL-6 and IL-1beta, p < 0.001). The proteomic analysis allowed to identify 49 proteins with an altered expression profile after stimulation with LPS and significantly modified by l-Arginine. These include proteins involved in the redox homeostasis of the cells (i.e. Xanthine Oxidase, Catalase, Aldehyde Oxidase), remodeling of the extracellular matrix (i.e. ADAMTSL4, Basigin, COL3A1) and cellular signaling (i.e. Fibrillin-1, Legumain, S100A13). The RT-PCR analysis confirmed the modifications of Fibrillin-1, ADAMTSL4, Basigin and Xanthine Oxidase, whose expression levels increase after stimulation with LPS and are reduced by l-Arginine (p < 0.05). CONCLUSIONS: l-Arginine prevents osteogenic differentiation of VICs and reduces matrix calcification. This effect is achieved through the modulation of proteins involved in the cellular redox system, remodeling of extracellular matrix and inflammatory activation of VICs.

Blood Pressure Variability and Therapeutic Implications in Hypertension and Cardiovascular Diseases.

Blood pressure (BP) is characterized by continuous dynamic and spontaneous oscillations occurring over lifetime and defining the so-called blood pressure variability (BPV). BPV has been associated with target organ damage, cardiovascular (CV) risk and death, suggesting the use of BPV as a new target in hypertension management in addition to mean BP values lowering. The purpose of the review is to focus on the therapeutic implications of BPV and summarize the effects of different drug classes on various types of BPV. Despite most first-line antihypertensive medications contribute to reduce both short and long term BPV, calcium channel blockers (CCBs) as monotherapy or fixed-combination therapy appear to be the most effective on BPV control. Further randomized interventional trials are needed to investigate which drug combinations are most appropriate according to patient CV risk stratification, in order to improve their CV outcomes.

Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE-/- mice.

INTRODUCTION: Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification. AIMS: To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice. RESULTS: 42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over-expression of COX-2 induced by inflammatory mediators. CONCLUSION: We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

Isolated systolic hypertension in the young: a position paper endorsed by the European Society of Hypertension.

: Whether isolated systolic hypertension in the young (ISHY) implies a worse outcome and needs antihypertensive treatment is still a matter for dispute. ISHY is thought to have different mechanisms than systolic hypertension in the elderly. However, findings from previous studies have provided inconsistent results. From the analysis of the literature, two main lines of research and conceptualization have emerged. Simultaneous assessment of peripheral and central blood pressure led to the identification of a condition called pseudo or spurious hypertension, which was considered an innocent condition. However, an increase in pulse wave velocity has been found by some authors in about 20% of the individuals with ISHY. In addition, obesity and metabolic disturbances have often been documented to be associated with ISHY both in children and young adults. The first aspect to consider whenever evaluating a person with ISHY is the possible presence of white-coat hypertension, which has been frequently found in this condition. In addition, assessment of central blood pressure is useful for identifying ISHY patients whose central blood pressure is normal. ISHY is infrequently mentioned in the guidelines on diagnosis and treatment of hypertension. According to the 2013 European Guidelines on the management of hypertension, people with ISHY should be followed carefully, modifying risk factors by lifestyle changes and avoiding antihypertensive drugs. Only future clinical trials will elucidate if a benefit can be achieved with pharmacological treatment in some subgroups of ISHY patients with associated risk factors and/or high central blood pressure.

Chronic kidney disease is associated with increased risk of venous thromboembolism recurrence.

INTRODUCTION: It is currently unclear whether chronic kidney disease (CKD) and the decrease in renal function can influence the risk of venous thromboembolism (VTE) recurrence. MATERIALS AND METHODS: We performed an ambispective observational study on 409 patients with a previous episode of VTE. All the patients were included in the retrospective analysis whereas a subgroup of 260 individuals, without history of recurrence and that stopped oral anticoagulation, were then followed-up for a mean of 52.3±20.7months. RESULTS: At the enrollment, subjects with history of recurrent VTE were prevalently male with higher blood pressure and lower eGFR. Prevalence of CKD (defined as eGFR<60ml/min/1.73m2) was higher in patients with previous VTE recurrence with an adjusted OR of 5.69 (IC95% 2.17-14.90, p<0.001) compared to patients with normal eGFR. Similar findings were obtained from the prospective study where an adjusted 5.32 HR for VTE recurrence was seen in patients with CKD compared to subjects with normal renal function (IC95% 1.49-18.95, p=0.010). An increase in the risk of recurrent VTE was also observed in patients with mild decrease in renal function (eGFR 60-90 vs ≥90ml/min/1.73m2 adjusted HR 2.84, IC95% 1.13-7.11, p=0.025). Moreover, a multivariate Cox regression analysis including eGFR as continuous variable showed that renal function decrease was independently associated with the risk of VTE recurrence (p=0.001). CONCLUSIONS: CKD and mild decrease in renal function are associated with a significant increase in the risk of recurrent VTE.

Cardiovascular risk and hypertension control in Italy. Data from the 2015 World Hypertension Day.

BACKGROUND: Cardiovascular diseases (CVD) are the first cause of death and disability in western countries. Despite therapeutic advances, their prevalence is constantly increasing. Detailed assessment of modifiable CV risk factors could improve CVD prevention and management. METHODS: to assess CV risk and hypertension control in a sample of the Italian population, individuals participating to the 2015 "World Hypertension Day" were interviewed in 62sites all over Italy. Blood pressure was measured with a validated auscultatory or oscillometric device and information on demography and prevalence of CVD risk factors was collected by an anonymous questionnaire. An ad-hoc modified version of the Systematic COronary Risk Evaluation (SCORE) system was then applied. RESULTS: 8657 recruited individuals (43%women, aged 56.68±16years) were subdivided into 3 age groups (40-49y, 50-59y, 60-69y) for analysis. CV risk was low in 62.4%, 18.0% and 0%; moderate in 26.0%, 66.0% and 62.5%; high/very high in 11.6%, 16% and 37.4%, respectively. Smoking was mainly responsible for increased CV risk among those aged 40-49y (26%smokers), while hypertension was the main factor in the whole sample and in subjects over 50y (36% and 42% respectively). Overall, BP control was unsatisfactory in 36% of individuals (28%, 48% and 31% of those who declared to be normotensive, hypertensive on treatment or unaware of their BP condition, respectively). CONCLUSIONS: In this sample of the Italian population, CV risk was alarmingly high, irrespectively of age, mostly due to presence of modifiable risk factors, including hypertension, which should thus be better addressed, especially in the youngsters.

Vascular Remodelling in Well-controlled Hypertensive Patients: The Challenge of Residual Risk Management.

BACKGROUND: Residual cardiovascular risk (RCVR) is an emerging issue in the clinical and therapeutic management of patients affected by hypertension. In fact, a number of clinical studies showed that even in case of optimal blood pressure (BP) control, the hypertensive patients still carry a sizeable increase in the CV risk as compared to normotensive individuals. METHODS: We will review the clinical evidence about the determinants and the impact of RCVR on hypertension, with a specific focus on the progression of vascular damage. RESULTS: The presence of RCVR in hypertensive patients is a significant phenomenon which challenges our clinical effort far beyond the reaching of BP targets. Although major determinants of RCVR are still undefined, there is a clear indication about the importance of an early and sustained control of BP values, so as to prevent the onset of target organ damage. In fact, our data and findings from the literature indicate that the &quot;pseudo-normalization&quot; of BP is not sufficient to abolish the risk of pro-atherogenic remodeling of arterial vessels. CONCLUSION: Additional studies are needed to establish whether the intervention on specific BP profiles and inflammatory mechanisms can have some clinical relevance in the management of RCVR. In the meanwhile, the precise phenotyping of the CV risk profile of each patient, coupled with a tailored pharmacological approach, represents the most effective strategy to hinder the progression of vascular damage and reduce the RCVR.

Intima-media thickness remodelling in hypertensive subjects with long-term well-controlled blood pressure levels.

Aim of this study was to evaluate in a long follow-up the carotid artery remodelling in a cohort of young hypertensive subjects having good blood pressure (BP) control. We studied 20 grade I hypertensives (HT) by assessing the B-mode ultrasound of mean carotid intima-media thickness (mean-IMT) and maximum IMT (M-MAX) in each carotid artery segment (common, bulb, internal), bilaterally. We compared their ultrasound measurements with those recorded 5 and 10 years earlier. While the first 5-year follow-up was observational, in the second 5-year follow-up, lifestyle modifications and/or pharmacological therapy were started to obtain well-controlled BP levels. Office BP was measured at the time of the ultrasound studies and every 6 months during the follow-up. BP levels were: 10 years 144/91 mmHg, 5 years 143/90 mmHg and 129 ± 79 mmHg at the time of the study. In the first 5-year observational follow-up, both mean-IMT and M-MAX increased (Δ 0.116 and Δ 0.165 mm, respectively, p < 0.0005). In the 5-year intervention follow-up, characterized by well-controlled BP, mean-IMT slightly but significantly increased (Δ 0.084 mm, p = 0.004), whereas M-MAX remained stable (Δ 0.026 mm). In our HT, well-controlled BP levels were able to prevent pro-atherogenic remodelling (expressed by M-MAX). Conversely, good BP control slightly decreased but did not stop the progression in mean-IMT, which is likely to reflect some hypertrophy of the arterial media layer.

Management of the hypertensive patient with elevated heart rate: Statement of the Second Consensus Conference endorsed by the European Society of Hypertension.

In June 2015, a panel of experts gathered in a consensus conference to plan updating recommendations on the management of the hypertensive patient with elevated heart rate (HR), previously released in 2006. The issues examined during that meeting and further discussed by the participants during the following months involved the assessment of HR, the relevance of HR as a cardiovascular risk factor, the definition of tachycardia and the treatment of the hypertensive patient with high HR. For the measurement of resting HR the panel experts recommended that scientific investigations focusing on HR should report information on length of resting period before measurement, information about temperature and environment, method of measurement, duration of measurement, number of readings, time interval between measurements, body position and type of observer. According to the panellists there is convincing evidence that HR is an important risk factor for cardiovascular disease and they suggest to routinely include HR measurement in the assessment of the hypertensive patient. Regarding the definition of tachycardia, the panellists acknowledged that in the absence of convincing data any threshold used to define tachycardia is arbitrary. Similarly, as there are no outcome studies of HR lowering in tachycardia hypertension, the panellists could not make practical therapeutic suggestions for the management of such patients. However, the experts remarked that absence of evidence does not mean evidence against the importance of tachycardia as a risk factor for cardiovascular disease and that long-term exposure to a potentially important risk factor may impair the patient's prognosis. The main aims of the present document are to alert researchers and physicians about the importance of measuring HR in hypertensive patients, and to stimulate research to clarify unresolved issues.