Despite celiprolol therapy, patients with vascular Ehlers-Danlos syndrome remain at risk of vascular events: A 12-year experience in an Italian referral center.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is an inherited connective tissue disorder characterized by arterial fragility. Celiprolol has been suggested to significantly reduce rates of vascular events in this setting, though real-world evidence is limited. The aim of this study was to report our experience with celiprolol therapy in vEDS management. METHODS: Patients with a genetically confirmed diagnosis of vEDS who were referred for outpatient consultation at the Brescia University Hospital between January 2011 and July 2023 were included. At each visit, patients' medical history, results of vascular imaging, and office blood pressure measurements were recorded. Celiprolol therapy was progressively titrated to the maximum tolerated dose of up to 400 mg daily, according to the patients' tolerance. RESULTS: Overall, 26 patients were included. Female sex was prevalent (62%). Mean (SD) age was 37 (16) years. Follow-up duration was 72 (41) months. At the last follow-up visit, all patients were on celiprolol therapy, 80% of whom were taking the maximum recommended dose. The yearly risk of symptomatic vascular events was 8.8%, the majority of which occurred after reaching the maximum recommended dose of celiprolol. No significant predictor of symptomatic vascular events was identified among patients' clinical characteristics. CONCLUSION: In our cohort, rates of celiprolol use were high and the drug was well tolerated overall. Nonetheless, the risk of symptomatic vascular events remained nonnegligible. Future studies should identify reliable predictors of major adverse events and explore additional therapeutic strategies that could further lower the risk of life-threatening events in this population.

Less sodium and more potassium to reduce cardiovascular risk.

An increase in the dietary consumption of salt is associated with a progressive increase in blood pressure (BP) values, and with an increase in the incidence of cardiovascular disease. Reducing the dietary intake of sodium in the population is a public health goal in many countries around the world. Numerous studies have described a linear relationship between high dietary salt intake and the development of arterial hypertension, as well as a negative association between high potassium intake and BP values. Furthermore, there is evidence that a reduction in salt consumption and an increase in potassium consumption can be associated with a decrease in BP values, improving the general state of health. Therefore, it would be desirable to further improve awareness of the risks associated with an excessive intake of salt and low potassium by maintaining public education campaigns and trying to overcome the numerous obstacles to a process of greater responsibility for people regarding nutrition.

Acute blood pressure elevation: Therapeutic approach.

International guidelines have suggested to avoid the term "hypertensive crisis" for the description of an acute and severe increase in blood pressure (BP) and to consider the definition of 'hypertensive emergencies' or 'hypertensive urgencies'. These two clinical presentations are characterized by the presence of high BP values but imply a different diagnostic and therapeutic approach. Hypertension awareness, treatment and control are slightly increased in the last years mostly in the United States and in some European nations. Nevertheless the prevalence of hypertensive emergencies is still high and remains associated to a higher mortality. International Guidelines have also given some recommendations regarding the target BP during treatment and the use of antihypertensive drugs in hypertensive emergencies, although the adherence to these indications is frequently suboptimal. The present paper is aimed to update the currently available data on the treatment of hypertensive emergencies.

Changes in left ventricular geometry during antihypertensive treatment.

The reduction of echocardiographic left ventricular (LV) mass and the change toward a less concentric geometry during antihypertensive treatment are independently associated with a better prognosis. Blood pressure-lowering treatment may reduce cardiac hypertrophy, although different effect on changes of LV mass have been reported among antihypertensive drug classes, while changes in echocardiographic evaluated LV geometry have not been systemically evaluated. It is not yet clear whether antihypertensive drugs may influence LV geometry. Our aim was to compare the effects of diuretics (D), beta-blockers (BB), calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARBS) on relative wall thickness (RWT) in patients with hypertension on the basis of prospective, randomized comparative studies. METHODS: MEDLINE, and the ISI Web of Sciences were searched for randomized clinical trials evaluating LV mass and geometry at baseline and end follow-up. We have performed a pooled pairwise comparisons of the effect of the 5 major drug classes on relative wall thickness changes, and of each drug class versus other classes statistically combined. RESULTS: We selected 53 publications involving 7684 patients. A significant correlation was observed between percent changes from baseline to end of treatment in LV mass and those in systolic BP (r = 0.44, p < 0.001). Reduction of LV mass was significantly greater with CCB than with BB (P <  0.02) without other significant differences between drug classes. Percent changes in RWT were related to percent changes in LV mass/LVmass index (r = 0.68, p = 0.016) and of SBP (r = 0.64 p < 0.033). RWT decreased during treatment with all classes of drugs, except the combination of BB and D; the decrease of RWT was less with diuretics and sympatholytic drugs. CONCLUSIONS: In studies evaluating the effect of different classes of antihypertensive drugs on LV mass, the reduction of relative wall thickness seems to be less during treatment with diuretics.

Modulation of Vascular Reactivity by Perivascular Adipose Tissue (PVAT).

PURPOSE OF REVIEW: In this review, we discuss the role of perivascular adipose tissue (PVAT) in the modulation of vascular contractility and arterial pressure, focusing on the role of the renin-angiotensin-aldosterone system and oxidative stress/inflammation. RECENT FINDINGS: PVAT possesses a relevant endocrine-paracrine activity, which may be altered in several pathophysiological and clinical conditions. During the last two decades, it has been shown that PVAT may modulate vascular reactivity. It has also been previously demonstrated that inflammation in adipose tissue may be implicated in vascular dysfunction. In particular, adipocytes secrete a number of adipokines with various functions, as well as several vasoactive factors, together with components of the renin-angiotensin system which may act at local or at systemic level. It has been shown that the anti-contractile effect of PVAT is lost in obesity, probably as a consequence of the development of adipocyte hypertrophy, inflammation, and oxidative stress. Adipose tissue dysfunction is interrelated with inflammation and oxidative stress, thus contributing to endothelial dysfunction observed in several pathological and clinical conditions such as obesity and hypertension. Decreased local adiponectin level, macrophage recruitment and infiltration, and activation of renin-angiotensin-aldosterone system could play an important role in this regard.

Changes in extracellular matrix in subcutaneous small resistance arteries of patients with essential hypertension.

BACKGROUND: In the development of hypertensive microvascular remodeling, a relevant role may be played by changes in extracellular matrix proteins. Aim of this study was the to evaluate some extracellular matrix components within the tunica media of subcutaneous small arteries in 9 normotensive subjects and 12 essential hypertensive patients, submitted to a biopsy of subcutaneous fat from the gluteal or the anterior abdominal region. PATIENTS AND METHODS: Subcutaneous small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. In addition, fibronectin, laminin, transforming growth factor-beta-1 (TGF-ß1) and emilin-1 contents within the tunica media were evaluated by immunofluorescence and relative immunomorphometrical analysis (immunopositivity % of area). The total collagen content and collagen subtypes within the tunica media were evaluated using both Sirius red staining (under polarized light) and immunofluorescence assay. RESULTS: Normotensive controls had less total and type III collagen in respect with hypertensive patients. Fibronectin and TGF-ß1 tunica media content was significantly greater in essential hypertensive patients, compared with normotensive controls, while laminin and emilin-1 tunica media content was lesser in essential hypertensive patients, compared with normotensive controls. A significant correlation was observed between fibronectin tunica media content and media to lumen ratio. CONCLUSIONS: Our results indicate that, in small resistance arteries of patients with essential hypertension, a relevant fibrosis may be detected; fibronectin and TGF-ß1 tunica media content is increased, while laminin and emilin-1 content is decreased; these changes might be involved in the development of small resistance artery remodeling in humans.

Relationship between different subpopulations of circulating CD4+ T lymphocytes and microvascular or systemic oxidative stress in humans.

BACKGROUND AND OBJECTIVE: Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes - TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. PATIENTS AND METHODS: In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. RESULTS: A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. CONCLUSIONS: Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1-Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage.

Effect of antihypertensive treatment with lercanidipine on endothelial progenitor cells and inflammation in patients with mild to moderate essential hypertension.

BACKGROUND: It has been demonstrated that circulating endothelial progenitor cells (EPCs) number reflects the endogenous vascular repair ability, with the EPCs pool declining in presence of cardiovascular risk factors. Several drugs, including dihydropyridine calcium channel blockers, have been reported to elicit antioxidant and anti-inflammatory properties, as well as to improve vascular remodeling and dysfunction. However, no data are available about the effects of lercanidipine on EPCs. The aim of the present study was therefore to investigate the effects of short-term treatment with lercanidipine on circulating EPCs, as well as on indices of inflammation and oxidative stress. PATIENTS AND METHODS: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Investigations were performed in basal condition, after appropriate wash out of previous treatments, and after 4 weeks of lercanidipine treatment. Inflammatory and oxidative stress markers were assessed by ELISA technique. Lin-/7AAD-/CD34+/CD133+/VEGFR-2 + and Lin-/7AAD-/CD34+/VEGFR-2 + cells were identified by flow cytometry and considered as EPCs. EPCs cells were expressed as number of cells per million Lin-mononuclear cells. RESULTS: Circulating EPCs were significantly increased after lercanidipine treatment (CD34+/CD133+/VEGFR-2 + cells: 78.3 ± 64.5 vs 46.6 ± 32.8; CD34+/VEGFR-2+: 87996 ± 165116 vs 1026 ± 1559, respectively, p < 0.05). A modest reduction in circulating indices of inflammation was also observed. CONCLUSIONS: In conclusion, lercanidipine is able to increase the number of circulating EPCs, possibly through a reduction of low-grade inflammation.

The Global Burden of Resistant Hypertension and Potential Treatment Options.

Resistant hypertension (RH) is defined as systolic blood pressure (SBP) or diastolic blood pressure (DBP) that remains .140 mmHg or .90 mmHg, respectively, despite an appropriate lifestyle and the use of optimal or maximally tolerated doses of a three-drug combination, including a diuretic. This definition encompasses the category of controlled RH, defined as the presence of blood pressure (BP) effectively controlled by four or more antihypertensive agents, as well as refractory hypertension, referred to as uncontrolled BP despite five or more drugs of different classes, including a diuretic. To confirm RH presence, various causes of pseudo-resistant hypertension (such as improper BP measurement techniques and poor medication adherence) and secondary hypertension must be ruled out. Inadequate BP control should be confirmed by out-of-office BP measurement. RH affects about 5% of the hypertensive population and is associated with increased cardiovascular morbidity and mortality. Once RH presence is confirmed, patient evaluation includes identification of contributing factors such as lifestyle issues or interfering drugs/substances and assessment of hypertension-mediated organ damage. Management of RH comprises lifestyle interventions and optimisation of current medication therapy. Additional drugs should be introduced sequentially if BP remains uncontrolled and renal denervation can be considered as an additional treatment option. However, achieving optimal BP control remains challenging in this setting. This review aims to provide an overview of RH, including its epidemiology, pathophysiology, diagnostic work-up, as well as the latest therapeutic developments.

Pheochromocytoma-Paraganglioma Syndrome: A Multiform Disease with Different Genotype and Phenotype Features.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors derived from the adrenal medulla and extra-adrenal chromaffin cells. Diagnosis is often challenging due to the great variability in clinical presentation; the complexity of management due to the dangerous effects of catecholamine excess and the potentially malignant behavior require in-depth knowledge of the pathology and multidisciplinary management. Nowadays, diagnostic ability has certainly improved and guidelines and consensus documents for treatment and follow-up are available. A major impulse to the development of this knowledge has come from the new findings on the genetic and molecular characteristics of PPGLs. Germline mutation in susceptibility genes is detected in 40% of subjects, with a mutation frequency of 10-12% also in patients with sporadic presentation and genetic testing should be incorporated within clinical care. PPGL susceptibility genes include "old genes" associated with Neurofibromatosis type 1 (NF1 gene), Von Hippel Lindau syndrome (VHL gene) and Multiple Endocrine Neoplasia type 2 syndrome (RET gene), the family of SDHx genes (SDHA, SDHB, SDHC, SDHD, SDHAF2), and genes less frequently involved such as TMEM, MAX, and FH. Each gene has a different risk of relapse, malignancy, and other organ involvement; for mutation carriers, affected or asymptomatic, it is possible to define a tailored long-life surveillance program according to the gene involved. In addition, molecular characterization of the tumor has allowed the identification of somatic mutations in other driver genes, bringing to 70% the PPGLs for which we know the mechanisms of tumorigenesis. This has expanded the catalog of tumor driver genes, which are identifiable in up to 70% of patients Integrated genomic and transcriptomic data over the last 10 years have revealed three distinct major molecular signatures, triggered by pathogenic variants in susceptibility genes and characterized by the activation of a specific oncogenic signaling: the pseudo hypoxic, the kinase, and the Wnt signaling pathways. These molecular clusters show a different biochemical phenotype and clinical behavior; they may also represent the prerequisite for implementing customized therapy and follow-up.

Influence of Perivascular Adipose Tissue on Microcirculation: A Link Between Hypertension and Obesity.

Alterations in microcirculation play a crucial role in the pathogenesis of cardiovascular and metabolic disorders such as obesity and hypertension. The small resistance arteries of these patients show a typical remodeling, as indicated by an increase of media or total wall thickness to lumen diameter ratio that impairs organ flow reserve. The majority of blood vessels are surrounded by a fat depot which is termed perivascular adipose tissue (PVAT). In recent years, data from several studies have indicated that PVAT is an endocrine organ that can produce a variety of adipokines and cytokines, which may participate in the regulation of vascular tone, and the secretory profile varies with adipocyte phenotype and disease status. The PVAT of lean humans largely secretes the vasodilator adiponectin, which will act in a paracrine fashion to reduce peripheral resistance and improve nutrient uptake into tissues, thereby protecting against the development of hypertension and diabetes. In obesity, PVAT becomes enlarged and inflamed, and the bioavailability of adiponectin is reduced. The inevitable consequence is a rise in peripheral resistance with higher blood pressure. The interrelationship between obesity and hypertension could be explained, at least in part, by a cross-talk between microcirculation and PVAT. In this article, we propose an integrated pathophysiological approach of this relationship, in order to better clarify its role in obesity and hypertension, as the basis for effective and specific prevention and treatment.

Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

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.

May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

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.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

Circulating endothelial progenitor cells, microvascular density and fibrosis in obesity before and after bariatric surgery.

It is not known whether, in obesity, the capillary density or the number of circulating endothelial progenitor cells (EPCs) are reduced, or whether fibrosis of small vessels is also present. In addition, possible effects of weight reduction on these parameters have never been evaluated. Therefore, we investigated EPCs and capillary density in 25 patients with severe obesity, all submitted to bariatric surgery, and in 18 normotensive lean subjects and 12 hypertensive lean patients as controls. All patients underwent a biopsy of subcutaneous fat during bariatric surgery. In five patients, a second biopsy was obtained after consistent weight loss, about 1 year later, during a surgical intervention for abdominoplasty. EPCs and capillary density were reduced in obesity, and EPCs were significantly increased after weight reduction. Vascular collagen content was clearly increased in obese patients. No significant difference in vascular collagen was observed between normotensive obese patients and hypertensive obese patients. After pronounced weight reduction, collagen content was nearly normalized. No difference in stress-strain relation was observed among groups or before and after weight loss. In conclusion, our data suggest that microvascular rarefaction occurs in obesity. EPCs were significantly reduced in obese patients. Pronounced weight loss induced by bariatric surgery seems to induce a significant improvement of EPC number, but not of capillary rarefaction. A pronounced fibrosis of subcutaneous small resistance arteries is present in obese patients, regardless of the presence of increased blood pressure values. Consistent weight loss induced by bariatric surgery may induce an almost complete regression of microvascular fibrosis.

State of the Art Review: Vascular Remodeling in Hypertension.

Although the gold-standard method for the assessment of structural alteration in small resistance arteries is the evaluation of the MLR by micromyography in bioptic tissues, new, noninvasive techniques are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles. These approaches represent a promising and interesting future perspective. Appropriate antihypertensive treatment is able to prevent the development of microvascular alterations or to induce their regression. Also, conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. In conclusion, the evaluation of microvascular structure is ready for clinical prime time, and it could, in the future, represent an evaluation to be performed in the majority of hypertensive patients, to better stratify cardiovascular risk and better evaluate the effects of antihypertensive therapy. However, for this purpose, we need a clear demonstration of the prognostic relevance of noninvasive measures of microvascular structure, in basal conditions and during treatment. Vascular remodeling may be frequently observed in hypertension, as well as in obesity and diabetes mellitus. An increased media to lumen ratio (MLR) or wall to lumen ratio (WLR) in microvessels is the hallmark of hypertension, and may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events. The molecular mechanisms underlying the development of vascular remodeling are only partly understood.

Subclinical Hypertension-Mediated Organ Damage (HMOD) in Hypertension: Atherosclerotic Cardiovascular Disease (ASCVD) and Calcium Score.

Calcium controls numerous events within the vessel wall. Permeability of the endothelium is calcium dependent, as are platelet activation and adhesion, vascular smooth muscle proliferation and migration, and synthesis of fibrous connective tissue. Double-helix computerized tomography is a noninvasive technique that can detect, measure, and compare coronary calcification in the coronary arteries. Despite some convincing evidence about the prognostic value and usefulness of coronary artery calcium score (CACS) in the stratification of cardiovascular risk in the high risk general population and also in hypertensive patients, current guidelines for the management of hypertension, do not include such evaluation among the recommended procedures to be performed in the majority of patients even with the intent to detect hypertension-mediated organ damage (HMOD) in an early phase. On the contrary, the European Society of Cardiology guidelines for the diagnosis and management of chronic coronary syndromes, the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, and the 2018 Cholesterol Clinical Practice Guidelines indicate that the evaluation of CACS may be of some usefulness in specific subpopulations, although this view is not accepted in the US Preventive Services Task Force document. Very recently, the European Society of Cardiology Guidelines on cardiovascular disease prevention in clinical practice stated that CACS estimation may be considered to improve risk classification around treatment decision thresholds. In conclusion, the use of CACS as a diagnostic tool is still controversial. While some evidence exists about is ability to improve stratification of cardiovascular risk in primary prevention, in particular in selected patients who are at intermediate or borderline risk of atherosclerotic cardiovascular disease, there is insufficient evidence to use it as a standard means to assess HMOD.

Microcirculation in Hypertension: A Therapeutic Target to Prevent Cardiovascular Disease?

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases, as well as microvascular eye diseases. Established hypertension leads to the chronic vasoconstriction of small arteries as well as to a decreased lumen diameter and the thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was firstly demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alterations in small resistance arteries; however, microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair the organ flow reserve, playing a crucial role in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage and related cardiovascular events, thus possessing a relevant prognostic relevance. New non-invasive techniques, such as scanning laser Doppler flowmetry or adaptive optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in terms of cardio- and cerebrovascular events. A rarefaction of the capillary network has also been reported in hypertension, which may contribute to flow reduction in and impairment of oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might contribute to microvascular angina, stroke, and renal dysfunction. In addition, they can be markers useful in monitoring the beneficial effects of antihypertensive treatment. Additionally, conductance arteries may be affected by a remodeling process in hypertension, and an interrelationship is present in the structural changes in small and large conductance arteries. The review addresses the possible relations between structural microvascular alterations and hypertension-mediated organ damage, and their potential improvement with antihypertensive treatment.

Prevalence of Cardiovascular Risk Factors and Related Medical and Lifestyle Interventions Among Italian Cardiovascular Specialists: A Proof-of-Concept Study.

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.