Screening of hypercortisolism among patients with hypertension: an Italian nationwide survey.

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.

Natural mutations of human XDH promote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: A novel mechanism to promote redox health?

Several rare genetic variations of human XDH have been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O2·- and H2O2 and nitrite (NO2-) reductase activity leading to nitric oxide (·NO). Since these products express important, and often diametrically opposite, biological activity, consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurring hXDH mutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide ·NO formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·- and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance of XDH mutations. We also show that, in presence of inorganic NO2-, XOR-driven O2·- production is substantially reduced. We suggest that targeting enzyme activity to enhance the NO2--reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease.

Perspectives on improving blood pressure control to reduce the clinical and economic burden of hypertension.

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.

Impact of simultaneous management of hypertension and hypercholesterolemia with ACE inhibitors and statins on cardiovascular outcomes in the Brisighella Heart Study: A 8-year follow-up.

BACKGROUND AND AIMS: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes. METHODS AND RESULTS: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05). CONCLUSION: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

Hypoxic events during non-obstetric abdominal surgery in pregnant women.

OBJECTIVE: Every year 0.5-2% of women undergo non-obstetric surgery in pregnancy. Hypoxic events with short-term and long-term consequences are one of the most frequent complications in surgery. There is only limited data available regarding the impact of these events. This review aims to analyze the current literature on hypoxic events occurring in non-obstetric abdominal surgery in pregnant women, focused on maternal and fetal outcomes. MATERIALS AND METHODS: We performed a non-systematic review of the literature, through a PubMed search using the key words "hypoxemia", "non-obstetric surgery", "surgical procedures", "pregnancy", "pregnant women" and "outcome". RESULTS: There is little data available regarding maternal and fetal outcomes after hypoxic episodes during non-obstetric surgery in pregnancy. In these cases, conservative intrauterine resuscitation maneuvers or immediate delivery should be taken into account. Perimortem cesarean section can be lifesaving for both mother and fetus when maternal collapse is non responsive to resuscitation procedures. Inaccurate information regarding maternal and fetal outcomes is due to the lack of robust data and the heterogeneity of the causes underlying maternal respiratory complications during surgery. CONCLUSIONS: Non-obstetric surgery during pregnancy must be performed when indicated. An expert multidisciplinary team, composed of obstetricians, surgeons, and anesthesiologists need to be included, giving appropriate attention to the physiological changes of respiratory, cardiovascular, and gastrointestinal system that occur during pregnancy. The shortest operative time and peri-operative assistance should be ensured. Complications, such as hypoxic events in pregnant patients need adequate assistance. Multidisciplinary cooperation, continuous training and simulation for anesthesiology and resuscitative procedures can guarantee this.

Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

Biomolecular basis related to inflammation in the pathogenesis of endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is a complex gynecological neoplasm with several clinical, histopathological and genetic features. Different hormonal, metabolic and biochemical axes are involved in pathogenesis. Obesity is a well-known risk factor for this disease and the role of local and systemic effects of adipose tissue, especially in the promotion of subclinical chronic inflammation, is an important issue. Indeed, inflammation is related to the pathogenesis of different tumors, including EC. This review aims to remark the role of obesity and inflammation in the pathogenesis of EC cancer through an exploration of the current literature. MATERIALS AND METHODS: We performed a comprehensive review of the literature through a PubMed search using key words and including English language papers looking at this topic. RESULTS: Only few authors analyzed the role of inflammatory cytokines released by adipose tissue in visceral abdominal fat depots. Tumor Necrosis Factor-α, Interleukin-6, Interleukin-1 Receptor Antagonist, Nuclear Factor-kB, Leptin, Adiponectin and C Reactive Protein were studied for cancer risk prediction models, risk stratification or targeted therapies. Furthermore, genetic studies evaluated the effect of inflammatory cytokines secreted by visceral adipocytes in the modulation of angiogenesis and signaling pathways such as PI3K/AKT/mTOR, that result altered in the pathogenesis of EC. CONCLUSIONS: The identification of inflammatory biomarkers released by adipose tissue, in the pathogenesis of EC, could be useful in improving diagnostic accuracy, identifying targets of therapy, suggesting useful lifestyle behaviors. A deeper knowledge of the genetic background of alterations in inflammatory pathway genes could better define the population exposed to a higher susceptibility to EC due to genetic polymorphisms. Future studies are needed to better understand this field.

Association Between the Serum Uric Acid Levels and Lacunar Infarcts in the Elderly.

Increasing evidence suggests that uric acid (UA) is a relevant risk factor for arteriolosclerosis and recent studies have demonstrated the positive relationship between UA concentrations and the severity of leukoaraiosis. However, the association between lacunar infarcts (LI) and UA levels has seldom been reported in the literature. The aim of our study was to assess whether serum UA levels may be related to the presence of LI. We recruited 242 patients (113 males and 129 females, aged 82.83 ± 6.49 years) from our Geriatric Department for whom CAT scans (CT) were available. Clinical and laboratory data was collected. Patients CT images were examined to identify the presence, the size, the number, and the location of LI. LI without neurological symptoms were considered silent LI. Serum UA levels were found to be positively associated with the presence (p = 0.0001), the number (p = 0.001), the size (p = 0.001), and the location of LI in the basal ganglia (p = 0.0038), the deep white matter (DWM) (p < 0.0001), and the pons (p = 0.0156). A significant association was also found between UA and silent LI (p = 0.0002). The prevalence of LI increased starting from UA levels of 5.7 mg/dl. Stepwise multiple regression analysis confirmed that UA was independently related with the presence, the number, the size, LI in the basal ganglia, the DWM, the pons, and with silent LI. Our study suggests a positive association between UA levels and LI, which is independent of traditional cardiovascular risk factors. This data suggests that UA plays an influential role on the physiopathology of LI and could represent a potential target to prevent cerebral microinfarcts.

Elevated serum uric acid concentration at discharge confers additive prognostic value in elderly patients with acute heart failure.

BACKGROUND AND AIMS: Elevated serum uric acid (sUA) concentrations have been associated with worse prognosis in heart failure (HF) but little is known about elderly patients. We aimed to assess long-term additive prognostic value of sUA in elderly patients hospitalized for HF. METHODS AND RESULTS: Clinical and echocardiographic characteristics of 310 consecutive elderly patients hospitalized for HF were collected. During index period, 206 had sUA concentrations available, which were obtained within 24 h prior to discharge; 10 patients were lost to follow-up, leaving 196 patients available. Patients had a median age of 77 (IQR 69-83) years, and were mostly male (64.5%). sUA ranges for tertiles I-III were: 1.5-6.1, 6.2-8.3, and 8.4-18.9 mg/dl, respectively. During a median follow-up of 27 months (IQR 10.5-39.5), 122 combined events occurred (87 deaths and 73 HF rehospitalizations). Four-year event-free survival for the combined endpoint was 46 ± 7% for tertile I, 34 ± 7% for tertile II, and 21 ± 5% for tertile III (P = 0.001). By multivariable Cox backward analysis, sUA was retained as a significant predictor. Compared with the lowest sUA tertile, tertile III showed a strong association with outcome, also after adjustment for other predictors (HR 1.84, 95% CI 1.16-2.93; P = 0.01). Importantly, addition of sUA to the other significant predictors of outcome resulted in improved risk classification (net reclassification improvement 0.19, P = 0.017). CONCLUSIONS: High sUA at discharge is a strong predictor of adverse outcome in elderly hospitalized for HF, and it significantly improves risk classification. Measuring sUA can be a simple and useful tool to identify high-risk elderly hospitalized for HF.

Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.

AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS: Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.

Polypill, hypertension and medication adherence: The solution strategy?

INTRODUCTION: Hypertension is an important global health challenge and a leading preventable risk factor for premature death and disability worldwide. In current cardiology practice, the main obstacles in the management of patients affected by hypertension are comorbidities and poor adherence to pharmacological treatments. The World Health Organization has recently highlighted increased adherence as a key development need for reducing cardiovascular disease. METHODS: Principal observational and clinical trial data regarding adherence, reductions in cardiovascular risk and safety of the polypill approach are summarized and reviewed. CONCLUSIONS: The polypill approach has been conclusively shown to increase adherence relative to usual care in all cardiovascular patients, furthermore, concomitant risk factor reductions have also been suggested. To date, the use of polypill could represent a solution strategy in patients affected by hypertension, comorbidities and non-adherence even though further studies, especially in the real-world settings, are needed in order to better understand its role in clinical practice.

Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial.

BACKGROUND: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn't often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. OBJECTIVE: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. DESIGN: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice. PARTICIPANTS: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. INTERVENTION: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. MEASUREMENTS: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). RESULTS: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. CONCLUSIONS: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

Role of nebivolol in the control and management of central aortic blood pressure in hypertensive patients.

Measurement of blood pressure (BP) using a brachial cuff sphygmomanometer is universally accepted for the diagnosis of hypertension and prediction of cardiovascular diseases. However, brachial systolic BP does not represent actual systolic BP in the central arteries which encounter cardiac load directly. Due to wave amplification from central to peripheral arteries, a significant difference exists between the two. Central BP measurements also account for arterial stiffness, vessel branching and vascular mechanics, unlike brachial BP. Emerging data suggests that hypertension can be diagnosed more accurately by central pressure indices as compared to brachial BP. Various non-invasive techniques are now available to measure central BP indices owing to recent technological advances. Recently, it has been reported that different classes of anti-hypertensive drugs display differential effects on brachial and central BPs. Nebivolol is a cardio-selective beta-blocker which targets central systolic BP and reduces it significantly along with brachial BP. In this article, we will review the current literature to evaluate the role of central BP to diagnose hypertension in detail. We will also assess the clinical evidence to evaluate the role of nebivolol in the management of elevated central systolic BP. Central BP indices offer better estimation of BP in central arteries and should be considered in routine clinical practice. Nebivolol has shown significant reduction in aortic pressure and wave reflection and improvements in endothelial dysfunction and arterial stiffness in hypertensive patients.

HPV-based strategy in follow-up of patients treated for high-grade cervical intra-epithelial neoplasia: 5-year results in a public health surveillance setting.

OBJECTIVE: Human papillomavirus (HPV) DNA testing is used increasingly for measuring the outcome of treatment for high-grade cervical intra-epithelial neoplasia (CIN2+). However, there is no international consensus regarding the number of tests and follow-up visits necessary in the post-treatment surveillance. A negative HPV DNA test result may permit relaxing the intensive post-treatment surveillance, but this possibility has not been standardized by all institutions to date. STUDY DESIGN: In 2008, the surveillance programme covering the Emilia-Romagna region in northern Italy adopted the HPV DNA test as a routine tool in the follow-up of women treated for CIN2+. Data from a prospective 5-year study are reported herein. Three hundred and ten patients treated for CIN2+ with a loop electrosurgical excision procedure underwent HPV DNA testing, cytology and colposcopy at 6 months post treatment. If all three tests were negative, women were tested at 18 months with cytology and colposcopy. If any of the three tests were positive, women were tested at 12, 18 and 24 months with cytology and colposcopy. When appropriate, a colposcopy-directed biopsy or CIN2+ retreatment was performed. After 18-24 months, the patients were tested annually with cytology for 3 years. RESULTS: None of the 172 (55%) women who were HPV negative at 6 months were found to have residual/recurrent CIN2+ during the surveillance period. In contrast, among the 138 (45%) HPV-positive women, 17 cases of residual/recurrent CIN2+ (17/138; 12.3%) were identified between 6 and 24 months. CONCLUSION: HPV DNA testing at six months after treatment for CIN2+ effectively identifies women who are disease free (HPV negative), and for whom a single follow-up at 18 months is sufficient.