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.

World Hypertension Day 2021 in Italy: Results of a Nationwide Survey.

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.

How to Improve Effectiveness and Adherence to Antihypertensive Drug Therapy: Central Role of Dihydropyridinic Calcium Channel Blockers in Hypertension.

Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.

Correlation between endothelial dysfunction and myocardial damage in acute phase of Tako-Tsubo cardiomyopathy: brachial flow mediated dilation as a potential marker for assessment of patient with Tako-Tsubo.

Takotsubo cardiomyopathy (TTC) is characterized by transient systolic ventricular dysfunction. It is supposed to be caused by a cathecolaminergic wave which leads to myocardial stunning through a massive action on beta2-adrenoreceptor. Moreover, beta2-receptor hyperactivity negatively influences endothelial function. It can be detected by brachial flow mediated dilation (b-FMD) which assesses endothelium regulated vasomotility. The study aim is to analyze the b-FMD variability during hospitalization in 50 patients admitted with TTC. In addition, we investigated a possible correlation between b-FMD at admission and both length of hospital stay (LOHS) and troponin I peak. We detected b-FMD by measuring the hypoxic induced vasoreactivity through assessing brachial artery dilation after 5 min of iatrogenic ischemia obtained by inflating a sphygmomanometer cuff. Artery diameter modifications were assessed by high-resolution ultrasound, and a dedicated software calculated accurately the percentage of dilation after ischemia by comparing it to the basal. These values were measured at admission and on discharge. The obtained values were compared for each patient to explore their variability during hospitalization. Moreover, the correlation between the b-FMD at admission and both the troponin I peak and the LOHS was investigated. There was a statistical significant difference between mean FMD measured at admission and at discharge (respectively 1.54 ± 0.34 and 8.92 ± 2.48%; p < 0.001). Moreover, we found a significant negative correlation between troponin I peak and FMD values at admission (r = - 0.7645; p < 0.001) and a significant inverse correlation between FMD at admission and LOHS (r = - 0.7543; p < 0.001). There is a significant improvement of b-FMD during hospitalization in patients admitted for Tako-Tsubo Cardiomyopathy. Moreover, for the first time, a direct correlation among b-FMD, troponin I peak and LOHS has been detected.

Ambulatory blood pressure parameters after canrenone addition to existing treatment regimens with maximum tolerated dose of angiotensin-converting enzyme inhibitors/angiotensin II type 1 receptor blockers plus hydrochlorothiazide in uncontrolled hypertensive patients.

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT). METHODS: ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were <130 and <80 mmHg, respectively. RESULTS: The addition of canrenone was associated with a reduction in systolic and diastolic BPs (24 h and daytime and nighttime; P<0.001), mean arterial pressures (P<0.001), and pulse pressures (P<0.01). The Δ 24 h systolic/diastolic BPs were -13.5±11.2/-8±8 mmHg and -16.1±13.5/-11.2±8.3 mmHg (50 and 100 mg/day, respectively). In the 50 mg arm, the 24 h systolic and diastolic BPs were normalized in 67.5% and 74% of the patients, respectively, and in 61.6% and 68.5% of the patients in the 100 mg arm, respectively (P<0.05; P= not significant for 50 vs 100 mg). The percentage of patients whose nocturnal decrease was >10% with respect to diurnal values did not change during combination therapy. CONCLUSION: Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension.

Efficacy and safety of two dosages of canrenone as add-on therapy in hypertensive patients taking ace-inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE-IT trial.

AIM: To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d). METHOD: In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3. RESULTS: Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (-20.26 vs -23.68 mm Hg for SBP, and -10.58 vs -12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded. CONCLUSION: Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178.

Microvascular impairment is associated with insulin resistance in euglycemic mild hypertensives.

BACKGROUND: Hypertension and diabetes are significantly associated with insulin resistance (IR), which could affect the vasodilatory capacity and microcirculation. The aim of the study was to verify whether IR is associated with a reduced microvascular blood flow in normoglycemic mild hypertensives. METHODS: Eighty-four untreated grade-1 hypertensives were equally divided, according to the IR homeostasis model assessment (HOMA) index, into three groups: IR-Low = 2.16 +/- 0.09 vs. IR-Medium = 3.77 +/- 0.09 vs. IR-High = 7.08 +/- 0.68 (P < 0.001) with similar sex distribution, office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and history of hypertension. They underwent ambulatory blood pressure monitoring (ABPM) and a laboratory stress session, during which blood pressure (BP), heart rate (HR), and skin blood flow (Laser Doppler) were taken on the forehead (LDF) and the hand (LDH), where the neuroadrenergic control of the microvascular blood flow is higher. Reactivity was calculated as "area-under-the-curve" (AUC) during arithmetic and cold pressor tests. Postischemic LDH served as the index of endothelial microcirculatory damage. RESULTS: ABPM confirmed the diagnosis of hypertension, but IR-High patients showed a reduced nighttime BP fall. They also demonstrated reduced LDH-AUC and LDF-AUC although BP-AUC and HR-AUC reactivity were similar. Postischemic LDH was lower in the IR-High group (P < 0.05), and the postischemic LDH change was progressively impaired in both IR-Medium and IR-High patients (P < 0.001). LDH-AUC (-0.305, P = 0.007) and postischemic LDH at 30 s (-0.217, P = 0.059) and 60 s (-0.248, P = 0.030) during hyperemia were associated with HOMA. Multiple regression analysis, with HOMA as the dependent variable, showed that BMI (beta = 0.336, P < 0.001) and LDH (beta = -0.239, P < 0.001), LDH-AUC (beta = -0.296, P < 0.01) and postischemic LDH change (beta = -0.321, P < 0.001) entered the equation. CONCLUSIONS: The findings suggest that IR is associated with functional microvascular constrictive impairment in normoglycemic mild hypertensives.

Measures of total stress-induced blood pressure responses are associated with vascular damage.

BACKGROUND: The role of cardiovascular reactivity to study hypertension, and the assessment methods, are still controversial. We aimed to verify the association of hypertension and vascular damage with several measures of cardiovascular response. METHODS: We studied 40 patients with normal-high (132 +/- 1/87 +/- 1 mm Hg) blood pressure (Group 1) and 80 untreated hypertensive subjects. Postischemic forearm vascular resistance (mFVR) served to differentiate hypertensive subjects (142 +/- 2/92 +/- 1 mm Hg v 143 +/- 2/94 +/- 2 mm Hg, P = NS) with a lower (Group 2) and higher (Group 3) hemodynamic index of vascular damage (4.8 +/- .05 v 6.3 +/- .09, P < .001). Reactivity was induced by Stroop (5') and cold pressor (90") tests. We measured muscular contraction and skin conductance as indices of emotional arousal, blood pressure, heart rate, forearm blood flow, and vascular resistance. Reactivity measures included: a) change from baseline, b) residualized score, c) cumulative change from baseline and residualized score, and d) total reactivity as area-under-the-curve (AUC), including changes occurring during baseline and recovery phases. RESULTS: The AUC of systolic blood pressure, diastolic blood pressure, and mFVR progressively increased in the groups (P < .001). Corrections of anthropometric and metabolic confounders were introduced in the Pearson equation between mFVR and reactivity measures. The AUC of SBP, DBP, and forearm blood flow and resistance demonstrated the highest (P < .001) correlation. On multiple regression analysis, AUC of SBP (beta = 0.634) and forearm blood flow (beta = -0.337) were predictive (P < .001) of vascular damage. CONCLUSIONS: Total blood pressure stress response, as AUC, including baseline and recovery phases, was significantly better associated with hypertension and vascular damage than the other reactivity measures studied.

Stress-induced hemodynamic responses are associated with insulin resistance in mild hypertensives.

BACKGROUND: High blood pressure (BP) and pulse pressure (PP) are recognized as independent risk factors for cardiovascular diseases, whereas insulin resistance (IR) is often associated with hypertension. The purpose of the study was to verify whether PP, taken at the doctor's office and during laboratory stimuli, might be predictive of IR. METHODS: Homeostasis model assessment insulin resistance index (HOMA) was calculated in 75 grade 1 hypertensives (148 +/- 2/92 +/- 1 mm Hg). Then, patients underwent hemodynamic reactivity study, induced by color word stroop, cold pressor, and handgrip tests. Stress response was calculated as total area (value x time) - baseline area (baseline value x time). RESULTS: Patients with similar age, history of hypertension, blood lipids and office blood pressure, but different HOMA (IR-low: 36.3 +/- 1.7 v IR-medium: 62.6 +/- 1.6, P <.001; IR-high: 123.1 +/- 12.8, P <.001 v IR-low and IR-medium), were divided in tertiles. They demonstrated a significant reactivity of systolic BP (IR-low: 225 +/- 58 v IR-medium: 448 +/- 43, P <.01; IR-high: 625 +/- 55, P <.001 v IR-low and P <.01 v IR-medium), PP (IR-low: -8 +/- 19 v IR-medium: 83 +/- 13, P <.001; IR-high: 201 +/- 19, P <.001 v IR-low and IR-medium), and stroke volume (SV) (IR-low: -138 +/- 43 v IR-medium: 1 +/- 27, P <.01; IR-high: 28 +/- 24, P <.001 v IR-low), but similar arterial stiffness (PP/SV) response. Partial correlation between IR and hemodynamic measurements showed a significant association only for systolic BP (0.54, P <.001), PP (0.686, P <.001), and SV (0.384, P <.001) reactivity, but not for office and baseline values. Stepwise multiple regression showed that only PP (beta: 0.634, P <.001) and, among hemodynamic determinants, SV (beta: 0.401, P <.001) response entered into the equation. CONCLUSIONS: The findings demonstrate that increased stress-induced PP, maintained by SV response, is the most predictive hemodynamic variable of reduced insulin sensitivity in mild hypertensives.