STRUGGLE FOR. Italian-Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023 for better control of classical modifiable risk factors in clinical practice.

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.

Incidence of hypertension in young transgender people after a 5-year follow-up: association with gender-affirming hormonal therapy.

In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with <30 years of age and had a follow-up >5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p < 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered.

Manidipine: an antihypertensive drug with positive effects on metabolic parameters and adrenergic tone in patients with diabetes.

Antihypertensive treatment of patients with diabetes should include those drugs with a positive effect on metabolic parameters. Most patients with diabetes require at least two antihypertensive agents. Combining a dihydropyridine calcium channel blocker with a renin-angiotensin-aldosterone system inhibitor is a rational approach. However, not all dihydropyridines are equal with respect to their effects on metabolic parameters. Thus, manidipine exerts a positive effect on insulin resistance. However, this effect has not been observed with amlodipine. On the other hand, the excessive activation of sympathetic nervous system has been related with an increase of insulin resistance, pulse pressure, and ankle edema rates. Compared with amlodipine, manidipine activates sympathetic nervous system to a lesser extent. As a result, treatment with manidipine represents a good option in hypertensive patients with diabetes.

Factors associated with the reduction of albumin excretion in diabetic hypertensive patients: differential effect of manidipine versus amlodipine.

AIMS: In AMANDHA trial, the addition of manidipine, but not amlodipine, in diabetic patients with uncontrolled hypertension, microalbuminuria and preserved renal function resulted in a large decrease of urinary albumin excretion (UAE) despite similar blood pressure (BP) reductions. Factors associated with the reduction of UAE were analyzed. METHODS: For this purpose, a multivariable analysis was performed. RESULTS: Although after 6 months of treatment, manidipine and amlodipine decreased BP to a similar extent, reductions of UAE were higher with manidipine. The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were associated with changes in UAE. CONCLUSION: The assigned treatment, changes in mean BP, sympathetic tone and glycemic control were independently associated with changes in UAE. Compared with amlodipine, manidipine reduced UAE to a higher extent, independently of BP reduction.

Complete Remission in Metastatic Pheochromocytoma Treated with Extensive Surgery.

Pheochromocytomas are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla. Malignant pheochromocytoma is defined as the presence of metastatic spread in tissues where chromaffin cells are not usually present. This case report describes the case of a relapsed malignant pheochromocytoma, spread to the right liver lobe, superior pole of the right kidney, posterior right hemidiaphragm, right hemidiaphragmatic pillar, inferior vena cava, and regional lymph nodes. After evaluation, an extensive surgery was performed, with resection of all the affected tissues and regional lymphadenectomy. No adjuvant treatment (radiotherapy or chemotherapy) was given. Complete clinical, biochemical, and radiological remission was achieved, with normalisation of metanephrine and normetanephrine. To date, six years after surgery, the patient remains asymptomatic and normotensive without taking any antihypertensive medication. We conclude that the therapeutic approach should be individualized in the case of metastatic pheochromocytoma. Extensive surgery can be considered as a treatment option, even in the case of multiple metastases, as it may be able to achieve complete remission of the disease, avoiding costly and potentially dangerous adjuvant therapies.

Manidipine in hypertensive patients with metabolic syndrome: the MARIMBA study.

OBJECTIVES: To evaluate the effects of manidipine versus amlodipine on blood pressure, albuminuria, insulin sensitivity, adiponectin, TNF-alpha and C-reactive protein in nondiabetic subjects with metabolic syndrome (ATP-III definition), including impaired fasting glucose (>5.6 mmol/l) and hypertension. METHODS: In total, 64 patients were recruited and randomly assigned to manidipine 20 mg versus amlodipine 10 mg (for 12 +/- 2 weeks). RESULTS: Blood pressure was reduced to a similar extent (p < 0.001) by both treatments. Albuminuria was significantly reduced by manidipine (-37.3%; p = 0.003), but not by amlodipine. C-reactive protein was reduced similarly (p < 0.01) by both treatments. Plasma adiponectin was increased (32.9%; p = 0.011) and plasma TNF-alpha was reduced by manidipine (-37.1%; p = 0.019), but neither was significantly changed by amlodipine. The HOMA insulin resistance index was significantly reduced by manidipine (-21.3%; p = 0.007), but not by amlodipine (-8.3%; p = 0.062). Tolerability with manidipine was superior to that with amlodipine (p = 0.04). CONCLUSION: These data support the added value of manidipine in renal and metabolic protection beyond blood pressure reduction in the treatment of hypertensive patients with metabolic syndrome.

Add-on manidipine versus amlodipine in diabetic patients with hypertension and microalbuminuria: the AMANDHA study.

The aim of this study was to compare the efficacy and safety of adding manidipine 20 mg versus amlodipine 10 mg to the treatment of diabetic patients with uncontrolled hypertension and microalbuminuria despite full-dose treatment with a renin-angiotensin system blocker for at least 6 months. Patients were randomized to receive manidipine (n = 61) or amlodipine (n = 30) in a 2:1 ratio for 6 months and monitored for microalbuminuria for an additional extension phase of 18 months. Manidipine and amlodipine decreased blood pressure values to a similar extent. Urinary albumin excretion was reduced by 65.5% with manidipine versus 20% with amlodipine (p < 0.01) at 6 months and 62.7 versus 16.6% (p < 0.01) at the end of the extension phase. Manidipine was better tolerated than amlodipine. Thus, the addition of manidipine, but not amlodipine, resulted in a large reduction in the urinary albumin excretion rate despite similar blood pressure reductions.

Prevalence, awareness, treatment and control of hypertension in a Canarian population. Relationship with glucose tolerance categories. The Guía Study.

OBJECTIVE: To estimate the prevalence, awareness, treatment and control of hypertension in a Canarian population; and their relationship with the glucose tolerance categories. DESIGN: From a population of 6355 subjects over 29 years old, 690 were chosen in a random sampling. Blood pressure measurements, a standard oral glucose tolerance test (excluding known diabetic patients), and a questionnaire on diabetes and hypertension history and medication use was performed. RESULTS: The total prevalence of hypertension was 50.3%; 62.0% of the hypertensive subjects were aware of their condition; 60.6% had their diastolic and 11.0% their systolic blood pressure controlled and 8.6% had both. For diabetic, glucose intolerant and normoglycemic subjects, the respective prevalences of hypertension were 79.4, 60.2 and 43.1% (higher in diabetic subjects, P < 0.001); the awareness of hypertension was 66.7, 61.8 and 59.5% (differences not significant); systolic blood pressure control was 4.8, 14.7 and 13.7% (lower in diabetic subjects, P = 0.017 versus glucose intolerant and P = 0.011 versus normoglycemic subjects); diastolic blood pressure control was 50.4, 72.1 and 63.2% (lower in diabetic subjects, P = 0.004 versus glucose intolerant and P = 0.025 versus normoglycemic subjects). There were no differences in the number and type of antihypertensive drugs among the different glucose tolerance categories. CONCLUSIONS: Blood pressure was comparable in our population and in other European populations. The prevalence of hypertension was higher, the awareness was similar, and control was worse in diabetic than in non-diabetic subjects; the drug treatment pattern was not different.