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Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Screening of Cushing Syndrome (CS) and Mild Autonomous Cortisol Secretion (MACS) in hypertensive patients is crucial for proper treatment. The aim of the study was to investigate screening and management of hypercortisolism among patients with hypertension in Italy., Methods: A 10 item-questionnaire was delivered to referral centres of European and Italian Society of Hypertension (ESH and SIIA) in a nationwide survey. Data were analyzed according to type of centre (excellence vs non-excellence), geographical area, and medical specialty., Results: Within 14 Italian regions, 82 centres (30% excellence, 78.790 patients during the last year, average 600 patients/year) participated to the survey. Internal medicine (44%) and cardiology (31%) were the most prevalent medical specialty. CS and MACS were diagnosed in 313 and 490 patients during the previous 5 years. The highest number of diagnoses was reported by internal medicine and excellence centres. Screening for hypercortisolism was reported by 77% in the presence of specific features of CS, 61% in resistant hypertension, and 38% in patients with adrenal mass. Among screening tests, the 24 h urinary free cortisol was the most used (66%), followed by morning cortisol and ACTH (54%), 1 mg-dexamethasone suppression test (49%), adrenal CT or MRI scans (12%), and late night salivary cortisol (11%). Awareness of referral centres with expertise in management of CS was reported by 67% of the participants, which reduced to 44% among non-excellence centres., Conclusions: Current screening of hypercortisolism among hypertensive patients is unsatisfactory. Strategies tailored to different medical specialties and type of centres should be conceived., (© 2024. The Author(s).)

Introduction: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study., Methods: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed., Results: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets., Conclusions: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies., (© 2024. The Author(s).)

Despite substantial progress in understanding the complex pathophysiology, hypertension remains a serious public health challenge affecting over 1.2 billion adults aged 30-79 years worldwide. Appropriate knowledge of the different pharmaceutical classes of antihypertensive agents and an understanding of the characteristics of individual molecules are essential to optimize clinical outcomes in patients with hypertension. We conducted a computer-assisted web interviewing (CAWI) quantitative survey in Italy, Poland, and Turkey to investigate physicians' prescriptions, knowledge, and perceptions of antihypertensive drugs with a focus on β-blockers, to assess antihypertensive usage patterns and the reasons underlying prescription choices. The survey findings show that β-blockers retain a pivotal role in the management of hypertension and are prescribed more often for patients with cardiovascular comorbidities than for patients with diabetic comorbidities. In all three countries, nebivolol is the only β-blocker among the ones analyzed which is consistently prescribed to 20% or more of patients and is overall the most prescribed one for the population with comorbid diabetes. In terms of specific β-blockers' features, this study revealed knowledge gaps that underline the need for educational activities focused on the differences among β-blockers, which are important in choosing the most suitable agent for individualized antihypertensive therapy., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side., Methods: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures., Results: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%)., Conclusions: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk., (© 2024. The Author(s).)

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort., Methods and Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P <0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P =0.004) and 1.150 (95% CI, 1.021-1.295, P =0.02), respectively., Conclusions: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

Nephroangiosclerosis (NAS) associated with hypertension continues to be one of the most causes of end stage renal diseases in Europe, but it is still poorly studied. The prevalence of NAS shows a large variability due to the difference among different countries regarding clinical presentations and the indication to perform renal biopsy. The study aimed to investigate the prevalence in biopsy-proven NAS patients and the association with hypertension and/or glomerulonephritis (GN). We included all patients referred for native kidney biopsy between 2003-2021 at Policlinic Umberto I of Rome. From 837 patients who underwent renal biopsy NAS was diagnosed in 80 (10.5%) patients. Serum creatinine was significantly higher in NAS [2.07 mg/dl (IQR 1.13-5.2) vs 1.1 mg/dl (IQR 0.8-2.1), p < 0.001] compared to patients without NAS. Hypertension was present in 45% of patients with NAS. Proteinuria was significantly higher in patients with mild-moderate NAS compared to patients with severe NAS [2.6 g/die (IQR 1-5) vs 1.5 g/die (IQR 0.86-2.3), p < 0.05]. We did not find any significant differences, including histological features, between NAS patients with hypertension and NAS patients without hypertension (p > 0.05). IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy were the most frequent GN associated. In conclusion no specific histological features are reported in NAS with and without hypertension. More information on the phenotype, clinical presentation and markers are needed to improve histological and clinical diagnostics., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

High blood pressure is the leading cause of death and disability globally and an important treatable risk factor for cardiovascular, cerebrovascular and chronic kidney diseases. Digital technology, including mobile health solutions and digital therapy, is expanding rapidly in clinical medicine and has the potential to improve the quality of care and effectiveness of drug treatment by making medical interventions timely, tailored to hypertensive patients' needs and by improving treatment adherence. Thus, the systematic application of digital technologies could support diagnosis and awareness of hypertension and its complications, ultimately leading to improved BP control at the population level. The progressive implementation of digital medicine in the national health systems must be accompanied by the supervision and guidance of health authorities and scientific societies to ensure the correct use of these new technologies with consequent maximization of the potential benefits. The role of scientific societies in relation to the rapid adoption of digital technologies, therefore, should encompass the entire spectrum of activities pertaining to their institutional role: information, training, promotion of research, scientific collaboration and advice, evaluation and validation of technological tools, and collaboration with regulatory and health authorities., (© 2023. The Author(s).)

Introduction: Physicians and researchers in the cardiovascular field are constantly engaged in the promotion of guidelines-directed preventive measures, but whether they are themselves adherent to the same recommendations was only sporadically examined., Aim: To assess awareness of self-exposure to cardiovascular risk factors and related management among cardiovascular specialists., Methods: During the National Conference of the Italian Society of Hypertension (October 2022), a pilot observational study on consecutive volunteer cardiovascular specialists was conducted. Participants underwent standard sitting and standing blood pressure (BP) measurements and answered a questionnaire regarding modifiable/non modifiable cardiovascular risk factors and related treatments. Based on self-declarations and actual measurements, BP was classified as optimal, normal, high-normal BP, and new hypertension in untreated participants, and as treated/untreated pre-existing hypertension. Controlled hypertension was defined as BP < 140/90 mmHg; age-adjusted lower targets were also applied, according to guidelines., Results: In total, 62 participants (30 F, mean age 43.2 ± 14.8 years) were enrolled; 79% reported regular physical activity; 53% of women and 38% of men were on a low-salt diet. After smoke (19.4%), dyslipidemia was the second most common risk factor (17.7%), often occurring with high BP (26.3%) and left untreated (36.7%). Pre-existing hypertension (11.3%) was often uncontrolled (57.1%) and associated with non-adherence to guidelines-directed lifestyle recommendations. About one in 12 participants was unaware of having high measured BP values., Conclusions: Despite the specific professional exposure, a margin for improvement in self cardiovascular risk factors awareness and management remains in this exploratory sample of cardiovascular specialists. This pilot research anticipates forthcoming, larger studies during national and international conferences., (© 2023. The Author(s).)

An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health., (© 2021 Wiley Periodicals LLC.)

Introduction: Cardiovascular diseases (CVD) are a leading cause of death worldwide, and several modifiable and unmodifiable risk factors contribute to this burden of disability and mortality. Thus, effective cardiovascular prevention relies on appropriate strategies to control risk factors within the frame of unmodifiable traits., Methods: We conducted a secondary analysis of treated hypertensive adults aged ≥ 50 years enrolled in Save Your Heart. CVD risk and hypertension control rates based on the 2021 updated European Society of Cardiology guidelines were evaluated. Comparisons with previous standards in terms of risk stratification and hypertension control rates were performed., Results: Among the 512 patients evaluated, with the application of the new parameters for fatal and non-fatal cardiovascular risk assessment, the proportion of individuals at high or very high risk rises from 48.7 to 77.1% of cases. A trend towards lower hypertension control rates was observed based on 2021 European guidelines compared with the 2018 edition (likelihood estimate for difference: 1.76%, 95% CI - 4.1 to 7.6%, p = 0.589)., Conclusions: In this secondary analysis on the Save Your Heart study, the application of the new parameters reported in the European Guidelines for Cardiovascular Prevention 2021 showed a hypertensive population with a very high probability of encountering a fatal or non-fatal cardiovascular event due to failure to control risk factors. For this reason, a better management of risk factors must be the main goal for the patient and all the involved stakeholders., (© 2023. The Author(s).)

Objective: In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events., Methods: Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr., Results: A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference)., Conclusion: Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Arterial hypertension (AH) and periodontitis are among the most common non-communicable chronic diseases worldwide. Besides sharing common risk factors, an increasing body of evidence supports an independent association between the two conditions, with low-grade systemic inflammation acting as the plausible biological link with increased cardiovascular risk. In 2021, the Italian Society of Arterial Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) have joined forces and published a joint report on the relationships between AH and periodontitis, reviewing the existing scientific evidence and underlining the need to increase awareness of the strong connection between the two conditions and promote treatment strategies for the control of gums inflammation in patients with AH. The current document extends the previous joint report, providing clinical practical guidelines aimed to support clinicians in the management of patients who suffer from or are at risk of being affected by both conditions. These recommendations are based on careful consideration of the available evidence as well as of the current guidelines on the management of periodontitis and AH and are supported by SIIA and SIdP., (© 2023. The Author(s).)

The progress in pharmacotherapy that has been made in recent years, including the introduction of very effective and safe lipid-lowering and antihypertensive drugs, has not yet translated into the expected universal control of blood pressure, lipid disorders and diabetes. In the STRUGGLE FOR Italian- -Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023, experts from five countries recounted several points about the paradigms of cardiological and cardiometabolic care for better control of classical modifiable risk factors in the year 2023. It is believed herein, that the need to intensify treatment, actively search for patients with cardiovascular risk factors, especially with arterial hypertension, hypercholesterolemia and diabetes, should go hand in hand with the implementation of the latest therapy, based on single pill combinations including proven, effective antihypertensive, lipid-lowering and antidiabetic molecules, many of which are listed in the present document. There is a need to use both new technological concepts, completely new drugs, as well as novel treatment concepts such as metabolic treatment in coronary artery disease, try to intensify the fight against smoking in every way, including the available range of drugs and procedures reducing the harm. This approach will provide substantially better control of the underlying cardiovascular risk factors in countries as varied as Italy, Poland, Spain, Uzbekistan and Vietnam.

Many modifiable and non-modifiable risk factors have been associated with hypertension. However, current screening programs are still failing in identifying individuals at higher risk of hypertension. Given the major impact of high blood pressure on cardiovascular events and mortality, there is an urgent need to find new strategies to improve hypertension detection. We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. We analysed the data set generated by the questionnaires administered during the World Hypertension Day from 2015 to 2019. A total of 20206 individuals have been included for analysis. We tested five ML algorithms, exploiting different balancing techniques. Moreover, we computed the performance of the medical protocol currently adopted in the screening programs. Results show that a gain of sensitivity reflects in a loss of specificity, bringing to a scenario where there is not an algorithm and a configuration which properly outperforms against the others. However, Random Forest provides interesting performances (0.818 sensitivity - 0.629 specificity) compared with medical protocols (0.906 sensitivity - 0.230 specificity). Detection of hypertension at a population level still remains challenging and a machine learning approach could help in making screening programs more precise and cost effective, when based on accurate data collection. More studies are needed to identify new features to be acquired and to further improve the performances of ML models., (© 2022. The Author(s).)

Aim: Periodontal diseases are associated with cardiovascular risk factors/diseases, and whether home oral hygiene practices are inversely related to the same conditions could carry relevant practical implications. We investigated the association of home oral hygiene habits with hypertension., Materials and Methods: During World Hypertension Day 2020, a nationwide cross-sectional survey was conducted on volunteers ≥18 years at 733 Italian pharmacies. Participants underwent standardized blood pressure (BP) measurement and answered a questionnaire on cardiovascular risk factors, oral health status, and home oral hygiene habits (toothbrushing daily frequency and manual/electric toothbrush). The association between home oral care habits and BP was assessed using multivariate logistic regression. Interactions between exposures and outcome were formally tested., Results: Among the 4506 participants (44.8% males, 66.1 ± 37.8 years), 47.6% reported brushing ≥3 times/day and 23.4% declared using the electric toothbrush. Brushing ≥3 versus &lt;3 times/day and use of electric versus manual toothbrush were associated with 19% (odds ratio [OR]: 0.81, 95% confidence interval [CI] 0.70-0.94) and 28% (OR: 0.72, 95% CI 0.61-0.85) lower odds of hypertension, respectively. No significant additive interaction was observed in the association of exposures with the outcome., Conclusions: Regular daily brushing and electric toothbrushing are associated with a better BP profile in a real-world context. Future interdisciplinary research is warranted to test these findings., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Purpose: Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements., Materials and Methods: The survey included 30 different items on how to perform the HBPM. It was developed by the 'Young Investigators' group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021., Results: A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p  < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p  < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p  < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque., Conclusions: Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Reduced access to dental care may increase cardiovascular risk; however, socioeconomic factors are believed to confound the associations. We hypothesized that the relation persists despite economic wellness and high education, with reduced access to dental care affecting cardiovascular risk at least in part through its effect on blood pressure (BP), possibly mediated by systemic inflammation., Methods: We first assessed the sociodemographic and clinical characteristics related to last dental visit timing (≤ or >6 months; self-reported) using national representative cross-sectional data. Then, the association of last dental visit timing with clinic BP was selectively investigated in highly educated, high income participants, further matched for residual demographic and clinical confounders using propensity score matching (PSM). The mediating effect of systemic inflammation was formally tested. Machine learning was implemented to investigate the added value of dental visits in predicting high BP over the variables included in the Framingham Hypertension Risk Score among individuals without an established diagnosis of hypertension., Results: Of 27,725 participants included in the population analysis, 46% attended a dental visit ≤6 months. In the PSM cohort (n = 2350), last dental visit attendance >6 months was consistently associated with 2 mmHg higher systolic BP (P = 0.001) and with 23 to 35% higher odds of high/uncontrolled BP compared with attendance ≤6 months. Inflammation mildly mediated the association. Access to dental care improved the prediction of high BP by 2%., Conclusions: Dental care use impacts on BP profiles independent of socioeconomic confounders, possibly through systemic inflammation. Regular dental visits may contribute to preventive medicine., (© 2021 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible., Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%)., Results: A total of 1354 participants (mean age 56.3 ± 15.3 years; 57.3% women; mean BP: 131.2 ± 17.5/81.6 ± 10.5 mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%)., Conclusions: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk., (© 2022. The Author(s).)

Hypertension is a major cardiovascular risk factor that is responsible for a heavy burden of morbidity and mortality worldwide. A critical aspect of cardiovascular risk estimation in hypertensive patients depends on the assessment of hypertension-mediated organ damage (HMOD), namely the generalized structural and functional changes in major organs induced by persistently elevated blood pressure values. The vasculature of the eye shares several common structural, functional, and embryological features with that of the heart, brain, and kidney. Since retinal microcirculation offers the unique advantage of being directly accessible to non-invasive and relatively simple investigation tools, there has been considerable interest in the development and modernization of techniques that allow the assessment of the retinal vessels' structural and functional features in health and disease. With the advent of artificial intelligence and the application of sophisticated physics technologies to human sciences, consistent steps forward have been made in the study of the ocular fundus as a privileged site for diagnostic and prognostic assessment of diverse disease conditions. In this narrative review, we will recapitulate the main ocular imaging techniques that are currently relevant from a clinical and/or research standpoint, with reference to their pathophysiological basis and their possible diagnostic and prognostic relevance. A possible non pharmacological approach to prevent the onset and progression of retinopathy in the presence of hypertension and related cardiovascular risk factors and diseases will also be discussed.

The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto "Our goal: achieve control. No setback: combine and check"., (© 2021. The Author(s).)

Hypertension and lipid disorders are two of the main cardiovascular risk factors. Both risk factors - if detected early enough - can be controlled and treated with modern, effective drugs, devoid of significant side effects, available in four countries as different as Italy, Spain, Poland, and Uzbekistan. The aim herein, was to develop this TIMES TO ACT consensus to raise the awareness of the available options of the modern and intensified dyslipidemia and arterial hypertension treatments. The subsequent paragraphs involves consensus and discussion of the deleterious effects of COVID-19 in the cardiovascular field, the high prevalence of hypertension and lipid disorders in our countries and the most important reasons for poor control of these two factors. Subsequently proposed, are currently the most efficient and safe therapeutic options in treating dyslipidemia and arterial hypertension, focusing on the benefits of single-pill combination (SPCs) in both conditions. An accelerated algorithm is proposed to start the treatment with a PCSK9 inhibitor, if the target low-density-lipoprotein values have not been reached. As most patients with hypertension and lipid disorders present with multiple comorbidities, discussed are the possibilities of using new SPCs, combining modern drugs from different therapeutic groups, which mode of action does not confirm the "class effect". We believe our consensus strongly advocates the need to search for patients with cardiovascular risk factors and intensify their lipid-lowering and antihypertensive treatment based on SPCs will improve the control of these two basic cardiovascular risk factors in Italy, Spain, Poland and Uzbekistan.

Background: Uric acid has long been considered responsible for a single specific disease, namely gout. In recent years, novel knowledge has emerged linking serum uric acid with a variety of conditions and related risk factors, from hypertension, metabolic syndrome, and type 2 diabetes, to fatal/nonfatal cardiovascular diseases and all-cause death, with the underlying mechanisms involving disrupted neurohormonal and metabolic signaling as well as oxidative stress and inflammation. Importantly, the cut-off value of serum uric acid that predicts the risk of incident events is within the range of normality and below the threshold for increased risk of gout. A large contribution to the advancement in knowledge in the cardiovascular implications of uric acid derives from the Italian study URic acid Right for heArt Health (URRAH)., Methods: The URRAH study is an Italian nationwide, multicenter retrospective, observational cohort study combining data from outpatients attending hypertension clinics, as well as individuals recruited in prospective observational cohort studies with a follow-up period of at least 20 years up to July 31 st , 2017. Data were retrospectively collected from different databases. At the end of the follow-up, the following hard endpoints were evaluated: fatal myocardial infarction; non-fatal acute myocardial infarction; heart failure; fatal stroke; non-fatal stroke; coronary revascularization., Results: A total of 22,714 subjects were included in the analysis. During a median follow-up time of 134 months, a total of 3279 deaths were recorded, of which 1571 were due to cardiovascular causes. Multivariate Cox regression analyses identified an independent association between serum uric acid concentrations and both total (HR=1.53, 95% CI 1.21-1.93, P<0.001) and cardiovascular deaths (HR=2.08, 95% CI 1.146-2.97; P<0.001). Of note, the cut-off values of serum uric acid that were identified as those able to predict total mortality were largely within the normal range (4.7 mg/dL, 95% CI 4.3-5.1 mg/dL). Similarly, the cut-off value that better predicted cardiovascular death was within the normal range (5.6 mg/dL, 95% CI 4.99-6.21 mg/dL). The information on serum uric acid levels provided a significant net reclassification improvement of 0.26 and 0.27 over the Heart Score risk chart for total and cardiovascular mortality, respectively (P<0.001). Serum uric acid levels ≥4.7 or <4.7 mg/dL incrementally predicted all-cause mortality over the Heart Score., Conclusions: The results of studies from the URRAH database further strengthen the role of uric acid in cardiovascular disease, including heart failure, and total mortality. The identified cut-off values support clinicians in investigating serum uric acid levels in their patients and to consider uric acid as an additional cardiovascular risk factor. Taken together, the published papers deriving from the URRAH database emphasize the role of uric acid in favoring cardiovascular events, and strongly suggest the existence of "grey" areas, i.e. close but lower than the "traditional" threshold for hyperuricemia, which deserve further characterization.

According to the most recent international guidelines, β-blockers maintain a central role in the management of hypertension, being recommended at any treatment step when there is a specific indication, such as heart failure, angina, postacute myocardial infarction, atrial fibrillation or pregnancy. However, β-blockers are not a homogeneous class: individual molecules differ in terms of pharmacological and clinical profile and are therefore suitable for different patient subtypes. In particular nebivolol, a third generation β 1 -selective β-blocker with vasodilating properties, neutral metabolic effects and good tolerability, proved to have advantages over other β-blockers, which makes the drug suitable in a wide variety of hypertensive patients with or without comorbidities.

Hyperkalemia is an elevated level of serum potassium (K + ) and does represent a life-threatening condition. In clinical practice, hyperkalemia mainly derives from an impaired renal K + excretion which, in turn, is usually caused by either acute or chronic renal failure. In concordance with this, hyperkalemia is very common in several chronic conditions, such as kidney disease, diabetes mellitus, heart failure, hypertension, and coronary heart disease. In all of these conditions the use of Renin-Angiotensin-Aldosterone System inhibitors (RAASIs), such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonist is widely recommended and further increases the risk of hyperkalemia. As hypertension is concerned, clinical trials suggest that the risk of hyperkalemia associated with RAASIs ranges from 2 to 10%. This often leads to a reduction or complete cessation of RAASIs, leaving patients without protective medications. Patiromer, a new oral potassium-binding agent, has been approved for clinical use in several countries, including Europe and US. Clinical studies have demonstrated that patiromer is effective in inducing a rapid and sustained K + reduction in various patient settings, including those where RAASIs are a fundamental component of cardiorenal protection. Patiromer is generally well tolerated and characterised by a good safety profile. Most importantly, patiromer use might allow the continuation of ACEIs and ARBs in hypertensive patients developing hyperkalemia during treatment and thereby favour a more effective and long-lasting cardiorenal protection., (© 2021. Italian Society of Hypertension.)

An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health., (© 2021. The Author(s).)

Introduction: Achieving hypertension control is beneficial regardless of age. Fixed-combination pills have the potential of increasing adherence to treatment, improving the benefit/risk ratio, and simplifying therapy, with resulting convenience especially in the elderly., Aim: We examined real-world antihypertensive treatment adherence and hypertension control rates in a cohort of Italian elderly individuals, enrolled in a prospective, pragmatic awareness-raising campaign on blood pressure (BP)., Methods: 13196 treated hypertensive elderly (mean age 73.2±7.5 years, 55.5% women) were recruited through opportunistic sampling, answered a brief questionnaire on antihypertensive therapy, and were followed-up for 6 months, when BP was measured as per routine care. Controlled hypertension was defined as BP < 140/90 mmHg. Real-world treatment adherence and hypertension control rates were evaluated at 6 months according to different treatment patterns (fixed-dose versus free combinations), using Yates correction for continuity to assess likelihood estimates for differences between treatments., Results: 10551 participants (80%) were on a single-pill therapy and 3445 were on a fixed combination therapy of two (24.8%) or three (1.3%) drugs. Individuals on a fixed combination therapy were more adherent to treatment than the counterparts (p < 0.001). Full adherence increased with the number of drugs/pill among single-pill users (47.5%, 68.5%, and 100% with 1, 2, or 3 drugs/pill; p < 0.001). Hypertension control rates were 70% and 65.2% (p = 0.001) according to fixed or free combinations of two drugs and 71% and 63.9% (p = 0.321) for fixed or free combinations of three drugs., Conclusions: Real-world data suggest that simplified treatment strategies and use of fixed combinations improve adherence to antihypertensive therapy and BP control in the elderly., (© 2021. The Author(s).)

Introduction: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy., Aims: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals., Methods: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors ("Abbasso la Pressione!") in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥ 18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits. Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication. Hypertension prevalence was defined as systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg. A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied., Results: Diabetic individuals (N = 5695, 12%) had higher rates of hypertension prevalence (80% vs. 54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs. 76.7%, p < 0.001), but lower hypertension control rates (36.1% vs. 39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics. Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001). Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age., Conclusions: Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world. Concomitant unfavorable metabolic features and unhealthy lifestyle habits might contribute to this observation.

The approach to hypertensive emergiencies (HE) and urgencies (HU) may be different according to local clinical practice, despite recent guidelines and position papers recommendations. The Italian Society of Hypertension (Società Italiana della Ipertensione Arteriosa, SIIA) developed an online survey, in order to explore the awareness, management and treatment of HU in Italy, sending by e mail a 12 items questionnaire to the members of the SIIA. The results show that the definition of HU was correctly identified by 62% of the responders. Most physicians identified the role of pharmacological therapy or legal/illegal substances abuse as possible cause of BP elevation; the use of a benzodiazepine drugs was considered worthwhile by 65% of responders. The prescription of diagnostic test and drug administration significantly differed from guidelines recommendations and only 57% of the physicians reported to treat HU with oral drug administration. Sub-lingual nifedipine was prescribed by 13% or responders. This survey shows the need to further spread the updated scientific information on the management and treatment of HE and HU, along with the improvement of the interrelationship with the general practitioner health system in Italy.

Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their management by non-specialists in the field. This document by the Italian Society of Hypertension summarizes the updated evidence linking sleep disorders to hypertension and cardiovascular diseases, the major underlying mechanisms, and the possible management strategies. A simplified, evidence-based diagnostic and therapeutic algorithm for comorbid hypertension and common sleep disorders, namely obstructive sleep apnoea and insomnia, is proposed.

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 ± 66.9 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 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 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., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory.

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension., Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders., Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively., Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Background: Hypertension control is a crucial measure to reduce cardiovascular (CV) risk, and blood pressure (BP) treatment targets have been recently revised to address this issue. However, achieving the recommended goal may be challenging., Objective: We aimed to assess the prevalence of uncontrolled hypertension, according to the US hypertension guidelines, among elderly participants in an Italian nationwide epidemiological survey, the relevant clinical correlates, and the agreement with the application of the European guidelines., Methods: Elderly (≥65y) volunteers enrolled in an Italian nationwide survey underwent BP measurement using standard protocols. Uncontrolled hypertension was defined as BP≥130/80 mmHg. Agreement of this definition with those from European guidelines (≥140/90 mmHg; ≥140/80 mmHg) was tested using Cohen's kappa. Selfreported information on modifiable/non-modifiable CV risk factors was also collected., Results: Of the 13,162 treated hypertensive elderly, 69.8% had uncontrolled hypertension. They tended to be overweight/obese men with diabetes. Overall agreement between US and European guidelines was poor to good (κ = 0.289, p<0.001 and κ = 0.691, p<0.001 based on the 140/90 and 140/80 mmHg threshold, respectively). Elderly participants with controlled hypertension were more likely to report a history of CV or chronic kidney disease. No difference in lifestyle habits was observed by BP control status., Conclusion: Real-world data identify limited concordance between guidelines in terms of BP target achievement among older hypertensive Italians and highlights the need to spread awareness of the CV risk, especially in the presence of diabetes and obesity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Fabry disease is a progressive, X-linked inherited lysosomal storage disorder where accumulation of glycosphingolipids increases the risk for early cardiovascular complications, including heart failure, stroke, and end stage renal disease. Besides disease-specific therapy, blood pressure (BP) control is of central importance in Fabry disease to reduce disease progression and improve prognosis. Both Fabry disease and hypertension are characterized by the activation of the innate component of the immune system, with Toll-like receptor 4 (TLR4) as a common trigger to the inflammatory cascade. The renin-angiotensin system (RAS) participates in the establishment of low-grade chronic inflammation and redox unbalance that contribute to organ damage in the long term. Besides exploiting the anti-inflammatory effects of RAS blockade and enzyme replacement therapy, targeted therapies acting on the immune system represent an appealing field of research in these conditions. The aim of this narrative review is to examine the issue of hypertension in the setting of Fabry disease, focusing on the possible determinants of their reciprocal relationship, as well as on the related clinical and therapeutic implications.

The management of arterial hypertension is very challenging in everyday clinical practice. Blood pressure control rates remain disappointingly low, despite intense efforts. Poor adherence to antihypertensive treatment is among the main causes of inadequate blood pressure control. Among the various parameters leading to poor adherence, medication adverse events seem to be the prevailing cause of treatment discontinuation. Β-blockers are a class of drugs commonly used in the management of hypertension. However, β-blockers use has been associated with various adverse events, among which, erectile dysfunction is a prevalent one. Accumulating evidence supports the detrimental role of β-blockers on erectile function. Older studies have shown contradictory findings, which however may be attributed to methodological errors related with the assessment of erectile function. More recent studies, however, unveiled the negative impact of this drug category on erectile function. Nevertheless, β-blockers represent a class of drugs with substantial within class heterogeneity. Nebivolol presents a unique mode of action through enhanced nitric oxide bioavailability that may be associated with benefits on erectile function. Indeed, studies of nebivolol have shown improvement in erectile function, suggesting that nebivolol represents the only exception in this class of drugs in terms of erectile function., (Copyright © 2020. Published by Elsevier B.V.)

Objective: In addition to high blood pressure variability (BPV), low BPV was associated with adverse cardiovascular prognosis in selected high-risk patients. We explored this issue in the Systolic Blood Pressure Intervention Trial (SPRINT) using a nonlinear approach with BPV as a continuous variable., Methods: Long-term systolic BPV (SBPV) (coefficient of variation, CoV %) was calculated on quarterly visits until a fatal/nonfatal cardiovascular event or all-cause mortality, excluding titration period and patients with missing visits. We used Cox proportional hazard models with penalized smoothing splines to shape the risk of outcomes against the continuum of SBPV (independent variable). Adjusted hazard ratios (aHR, 95% CI) were calculated using the reference range derived from the nonlinear model. Sensitivity analysis based on propensity score matching (PSM) was performed., Results: The association of SBPV with fatal/nonfatal cardiovascular events was J-shaped, whereas that with all-cause mortality was linear. After multivariate adjustment, however, the only significant associations remained that of low SBPV (CoV <5%) with cardiovascular events (hazard ratio 1.85, 95% CI 1.24-2.75, P = 0.003), and of high SBPV (CoV >10%) with the composite of cardiovascular events and all-cause mortality (hazard ratio 1.35, 95% CI 1.02-1.80; P = 0.037). Low SBPV was associated with ischemic heart disease (hazard ratio 2.76, 95% CI 1.55-4.91; P < 0.001). There was a significant U-shaped association of SBPV with cardiovascular events in the PSM cohort., Conclusion: Nonlinear modeling indicates that low and high long-term SBPV have prognostic relevance in high-risk hypertensive individuals from SPRINT. Randomized trials are needed to test these findings and their potential therapeutic implications.

Background: Cardiovascular diseases (CVD) including hypertension, are characterized by underlying systemic inflammation. Periodontitis, which can impact the systemic inflammatory burden has recently been linked to high blood pressure (BP). However, the relationship of gingival bleeding, as an easily accessible marker of periodontal disorder, with hypertension, remains unclear., Methods: Survey-based propensity score matching (PSM) incorporating major confounders shared between hypertension and periodontal diseases was applied to cross-sectional NHANES III data from 5396 adults at least 30 years old who underwent BP measurement and periodontal examination, identifying two matched groups with and without gingival bleeding. The association of bleeding gums with SBP (mmHg) and high/uncontrolled BP was then assessed with generalized additive models incorporating inflammatory markers. Stratification by periodontal status (healthy; gingivitis; stable periodontitis; unstable periodontitis) was performed. Variables importance was estimated using machine learning., Results: Gingival bleeding (gingivitis; unstable periodontitis) was independently associated with +2.6 mmHg (P < 0.001) SBP compared with no bleeding (healthy periodontium; stable periodontitis), and with greater odds (OR = 1.42; 95% CI = 1.19-1.68; P < 0.001) of high/uncontrolled BP. Participants with unstable periodontitis had higher SBP than those with stable periodontitis (+2.1 mmHg; P < 0.001) or gingivitis (+5.3 mmHg; P < 0.001). Unstable periodontitis and gingivitis were consistently associated with increased risk of high/uncontrolled BP (OR = 1.65, 95% CI = 2.14-1.82; OR = 1.49, 95% CI = 1.22-1.82, respectively). Inflammatory markers allowed a maximum of 12% gain in the models' predictive power., Conclusion: Gingival bleeding contributes to shaping the relationship between periodontal diseases and BP, but the burden represented by periodontitis is also crucial. Periodontal evaluation might be of importance in difficult to control hypertension.

Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were recorded. At least 1 preexisting condition was observed in 73.4% of patients, with hypertension being the most represented (54.9%). One hundred eighty-eight deaths were recorded (11.8%; mean age, 79.6±0.9 years). In nonsurvivors, older age, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery diseases, and heart failure were more represented than in survivors. The Charlson Comorbidity Index was significantly higher in nonsurvivors compared with survivors (4.3±0.15 versus 2.6±0.05; P <0.001). ACE (angiotensin-converting enzyme) inhibitors, diuretics, and β-blockers were more frequently used in nonsurvivors than in survivors. After correction by multivariate analysis, only age ( P =0.0001), diabetes mellitus ( P =0.004), chronic obstructive pulmonary disease ( P =0.011), and chronic kidney disease ( P =0.004) but not hypertension predicted mortality. Charlson Comorbidity Index, which cumulates age and comorbidities, predicts mortality with an exponential increase in the odds ratio by each point of score. In the COVID-19 outbreak, mortality is predicted by age and the presence of comorbidities. Our data do not support a significant interference of hypertension and antihypertensive therapy on COVID-19 lethality. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT04331574.

High blood pressure (BP) and periodontitis are two highly prevalent conditions worldwide with a significant impact on cardiovascular disease (CVD) complications. Poor periodontal health is associated with increased prevalence of hypertension and may have an influence on BP control. Risk factors such as older age, male gender, non-Caucasian ethnicity, smoking, overweight/obesity, diabetes, low socioeconomic status, and poor education have been considered the common denominators underpinning this relationship. However, recent evidence indicates that the association between periodontitis and hypertension is independent of common risk factors and may in fact be causal in nature. Low-grade systemic inflammation and redox imbalance, in particular, represent the major underlying mechanisms in this relationship. Neutrophil dysfunction, imbalance in T cell subtypes, oral-gut dysbiosis, hyperexpression of proinflammatory genes, and increased sympathetic outflow are some of the pathogenetic events involved. In addition, novel findings indicate that common genetic bases might shape the immune profile towards this clinical phenotype, offering a rationale for potential therapeutic and prevention strategies of public health interest. This review summarizes recent advances, knowledge gaps and possible future directions in the field.

Children are defined as hypertensive when their blood pressure values equal or exceed the 95th percentile of the blood pressure value distribution in a pediatric population, according to gender, age and height. The population on which reference tables are based is of fundamental importance to establish the threshold values for the diagnosis of hypertension in pediatric age. Before 2017, both American and European guidelines used nomograms created in the same reference population which included children of all weight classes. Given the close and well-known association between hypertension and excess weight in childhood, the 2017 American guidelines proposed new reference nomograms excluding subjects with overweight and obesity from the "historical" reference population. Furthermore, the new American guidelines suggested a fixed cut-off of 130/80 mmHg, starting from 13 years and regardless of gender and height, to make the diagnosis of hypertension. In this document, the Italian Hypertension Society (SIIA) and the Italian Pediatric Society (SIP) jointly discuss a number of issues raised by the new American guidelines that involve the entire medical community, and also address the definition of arterial hypertension in the transition phase between childhood and adulthood.

Renal denervation is a device-based procedure for hypertension for which safety and efficacy has been demonstrated. At present, its clinical use is still matter of debate, despite the most recent clinical trials have shown promising results with new-generation devices in various hypertensive populations. This position paper was deemed necessary by the Italian Society of Arterial Hypertension, in order to provide indications about the applications of renal denervation in the clinical setting. A state-of-the art review of the literature, focusing on safety and efficacy data, is provided. Furthermore, based on current evidence and expert consensus, clinical profiles of possible candidates for renal denervation are proposed. The selection process should take into account not only blood pressure values, global cardiovascular risk profile, but also drug adherence and tolerability and patient preferences. This position paper also defines minimum requirements for renal denervation selection centers and a flowchart for the difficult-to-treat hypertensive patient. Further studies are needed to support these preliminary indications, which are based on expert-consensus only.

Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease. The available literature, indeed, presents contrasting results, all concentrated in experimental models. Evidence in humans is lacking that those mechanisms are actually occurring in the present COVID-19 outbreak. Here we present the reasoned statement of the Italian Society of Hypertension to maintain ongoing antihypertensive treatments. Furthermore, the Italian Society of Hypertension presents its own initiative to investigate the issue using an online questionnaire to collect relevant data in human disease.

Introduction: The most recent European guidelines on hypertension redefined office blood pressure (BP) treatment targets according to age strata and cardiovascular (CV) risk profile., Aim: To evaluate proportions of adult outpatients achieving office BP treatment targets recommended by current compared to previous hypertension guidelines., Methods: We extracted data from medical databases of adult outpatients followed in three excellence centers in hypertension (Rome, Italy; L'Aquila, Italy; Valencia, Spain). Office BP treatment targets were defined according to either 2013 ESH/ESC guidelines (< 140/90 mmHg in non-diabetic individuals aged 18-80 years, < 150/90 mmHg in those aged ≥ 80 years, and < 140/85 mmHg in diabetic individuals), or 2018 ESC/ESH guidelines: (< 130/80 mmHg in individuals aged 18-65 years, < 140/80 mmHg in those aged 65-79 and ≥ 80 years). SCORE risk was assessed in all patients., Results: From an overall sample of 14,229 adult subjects, 4049 (28.5%) resulted normotensive individuals, 3088 (21.7%) were untreated and 7092 (49.8%) treated hypertensive outpatients. Treated hypertensives showed significantly higher ESC score risk (8.3 ± 13.0% vs. 3.9 ± 8.4%; P < 0.001) and lower systolic/diastolic BP (140.6 ± 18.8/83.9 ± 11.5 vs. 148.3 ± 14.2/94.7 ± 10.1 mmHg; P < 0.001) than untreated hypertensives. Compared to previous guidelines, BP control significantly lowered in non-diabetic outpatients (n = 5847) of all age groups [18-65 years: (13.1% vs. 42.9%), 65-79 years (25.8% vs. 42.5%) and ≥ 80 years (29.1% vs. 66.0%); P < 0.001 for all comparisons]; similar reductions were observed in diabetic outpatients (n = 1245) [18-65 years (32.7% vs. 14.8%), 65-79 years (37.3% vs. 24.7%) and ≥ 80 years (47.1% vs. 27.9%); P < 0.001]., Conclusions: According to the recommended new office BP treatment targets, the proportions of treated uncontrolled hypertensive patients substantially increased. These findings should prompt a tighter application of therapeutic recommendations and, thus, highlight the need for improving hypertension management and control strategies.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; P <0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively ( P <0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.

Aim: Periodontitis is a relapsing-remitting disease. Compared with bleeding on probing (BoP), expression of disease activity, periodontal inflamed surface area (PISA), incorporates chronic disease parameters. We tested the association of PISA and BoP with blood pressure (BP) in NHANES III., Materials and Methods: A total of 8,614 subjects (≥30 years) with complete periodontal and BP examinations were enrolled. PISA was derived from periodontal probing depth and BoP. The association of PISA and BoP with high/uncontrolled BP was examined by multiple-adjusted models. Inflammatory markers were tested as possible mediators. A machine learning (ML) approach was used to define the relative importance of PISA and BoP and estimate the power of BP status prediction., Results: Compared to no inflammation, severe PISA and BoP were associated with 43% (p < .001) and 32% (p = .006) higher odds of high/uncontrolled BP (≥130/80 mmHg), and with higher systolic BP by ≈4 (p < .001) and 5 (p < .001) mmHg, respectively. Inflammatory markers appeared to mediate this association with various extents, without threshold effect. BoP predicted high/uncontrolled BP more efficiently than PISA using ML., Conclusion: PISA and BoP describe the association of periodontal inflammation and hypertension with subtle differences. The contribution of local inflammation to the global inflammatory burden might explain the observed findings., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Observational evidence supports an inverse association between hypovitaminosis D and blood pressure (BP), but intervention data have failed to demonstrate beneficial effects of vitamin D supplementation on BP. Following the downwards redefinition of hypertension treatment targets and the need to better identify individuals at greater risk for uncontrolled BP, our aim was to test the association of serum vitamin D levels with the definition of uncontrolled BP according to European guidelines in treated hypertensive adults., Methods: We retrospectively analyzed cross-sectional, nationally representative data from treated hypertensive adults aged at least 18 years with available serum 25 (OH)D measurements. BP was examined as continuous (mmHg) and categorical (at or above treatment goal, as recommended by guidelines) variable; BP means and odds ratios for uncontrolled BP according to vitamin D levels were calculated using progressively adjusted models., Results: Treated hypertensive adults with vitamin D deficiency had higher mean BP (+2.4/3.5 mmHg; P < 0.01) and 25-29% higher risk of uncontrolled BP compared to those with vitamin levels at least 75 nmol/l. These results were confirmed across age, sex, and racial/ethnic strata. Vitamin D insufficiency was associated with higher BP by 0.5/2.4 mmHg, but not with an increased risk of uncontrolled hypertension., Conclusions: 25 (OH)D levels might indicate host-specific features related to poor BP control. The attempt to use a biomarker of exposure as an indicator of need for treatment risks to be misleading.