The GH/IGF-1 Axis and Heart Failure

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis regulates cardiac growth, stimulates myocardial contractility and influences the vascular system. The GH/IGF-1 axis controls intrinsic cardiac contractility by enhancing the intracellular calcium availability and regulating expression of contractile proteins; stimulates cardiac growth, by increasing protein synthesis; modifies systemic vascular resistance, by activating the nitric oxide system and regulating non-endothelial-dependent actions. The relationship between the GH/IGF-1 axis and the cardiovascular system has been extensively demonstrated in numerous experimental studies and confirmed by the cardiac derangements secondary to both GH excess and deficiency. Several years ago, a clinical non-blinded study showed, in seven patients with idiopathic dilated cardiomyopathy and chronic heart failure (CHF), a significant improvement in cardiac function and structure after three months of treatment with recombinant GH plus standard therapy for heart failure. More recent studies, including a small double-blind placebo-controlled study on GH effects on exercise tolerance and cardiopulmonary performance, have shown that GH benefits patients with CHF secondary to both ischemic and idiopathic dilated cardiomyopathy. However, conflicting results emerge from other placebo-controlled trials. These discordant findings may be explained by the degree of CHF-associated GH resistance. In conclusion, we believe that more clinical and experimental studies are necessary to exactly understand the mechanisms that determine the variable sensitivity to GH and its positive effects in the failing heart

Effects of growth hormone on exercise capacity and cardiopulmonary performance in patients with chronic heart failure.

BACKGROUND: Because GH exerted beneficial effects in various experimental models of heart failure, we investigated the effects of GH on physical exercise capacity and cardiopulmonary performance in patients with dilated cardiomyopathy and chronic heart failure (CHF). METHODS: Twenty-two patients with CHF (New York Heart Association functional class II-III) underwent spirometry and a symptom-limited, cardiopulmonary exercise testing before and after 3 months of GH (n = 11; seven males; seven idiopathic; 57 +/- 11 yr; 4 IU sc every other day) or placebo (n = 11; eight males; six idiopathic; 54 +/- 10 yr) administration, in a randomized, double-blind trial. Background CHF therapy remained unchanged. RESULTS: GH, but not placebo, increased IGF-I serum concentration (from 144 +/- 35 to 293 +/- 58 ng/ml; P < 0.005) and improved New York Heart Association functional class (from 2.4 +/- 0.5 to 1.8 +/- 0.4; P < 0.005), exercise duration (from 831 +/- 273 to 925 +/- 266 sec; P < 0.005), peak power output (from 245 +/- 127 to 280 +/- 132 W; P < 0.05), peak minute ventilation (from 52.5 +/- 16.1 to 61.3 +/- 17.3 liters/min; P < 0.05), peak oxygen consumption (from 19.8 +/- 5.6 to 25.1 +/- 5.6 ml/kg.min; P < 0.005), and anaerobic threshold (from 14.9 +/- 4.8 to 20.0 +/- 4.5 ml/kg.min; P < 0.005) without affecting lung function parameters. Furthermore, the slope of the relationship between minute ventilation and pulmonary carbon dioxide production (ventilatory efficiency) decreased from 34.7 +/- 5.1 to 31.7 +/- 5.3 (P < 0.005), whereas the slope of the relation between percent predicted heart rate reserve used and percent observed metabolic reserve used (chronotropic index) rose from 0.57 +/- 0.20 to 0.69 +/- 0.18 (P < 0.005). CONCLUSION: Given the predictive value of physical exercise capacity and cardiopulmonary performance in CHF progression, these data provide additional insights into the mechanisms by which GH may potentially benefit CHF patients

The Negative Impact of Insulin Resistance/Hyperinsulinemia on Chronic Heart Failure and the Potential Benefits of Its Screening and Treatment

This opinion article highlights the potential alterations caused by insulin resistance and hyperinsulinemia on the cardiovascular system and their negative impact on heart failure (HF), and describes the potential benefits of an early screening with consequent prompt treatment. HF is the final event of several different cardiovascular diseases. Its incidence has been increasing over the last decades because of increased survival from ischemic heart disease thanks to improvements in its treatment (including myocardial revascularization interventions) and the increase in life span. In particular, incidence of HF with preserved ejection fraction (HFpEF) is significantly increasing, and patients with HFpEF often are also affected by diabetes mellitus and insulin resistance (IR), with a prevalence > 45%. Concentric left ventricular (LV) remodeling and diastolic dysfunction are the main structural abnormalities that characterize HFpEF. It is well documented in the literature that IR with chronic hyperinsulinemia, besides causing type 2 diabetes mellitus, can cause numerous cardiovascular alterations, including endothelial dysfunction and increased wall thicknesses of the left ventricle with concentric remodeling and diastolic dysfunction. Therefore, it is conceivable that IR might play a major role in the pathophysiology and the progressive worsening of HF. To date, several substances have been shown to reduce IR/hyperinsulinemia and have beneficial clinical effects in patients with HF, including SGLT2 inhibitors, metformin, and berberine. For this reason, an early screening of IR could be advisable in subjects at risk and in patients with heart failure, to promptly intervene with appropriate therapy. Future studies aimed at comparing the efficacy of the substances used both alone and in association are needed

Cardiovascular and metabolic effects of Berberine

Berberine (BBR) is a natural alkaloid isolated from the Coptis Chinensis. While this plant has been used in Ayurvedic and Chinese medicine for more than 2500 years, interest in its effects in metabolic and cardiovascular disease has been growing in the Western world in the last decade. Many papers have been published in these years reporting beneficial effects in carbohydrate and lipid metabolism, endothelial function and the cardiovascular system. In this review, we report a detailed analysis of the scientific literature regarding this topic, describing the effects and the underlying mechanisms of BBR on carbohydrate and lipid metabolism, endothelial function and the cardiovascular system

Insulin resistance/hyperinsulinemia: an important cardiovascular risk factor that has long been underestimated

Cardiovascular mortality is still excessively high, despite the considerable progress made in the prevention and treatment of cardiovascular diseases. Although many cardiovascular risk factors (such as arterial hypertension, hypercholesterolemia, diabetes, etc.), identified in the general population, are being promptly treated, to date little consideration is given to a cardiovascular risk factor which we believe has largely demonstrated in the scientific literature of the last three decades that, if neglected, can produce a series of relevant negative effects on the cardiovascular system: insulin resistance (IR)/hyperinsulinemia (Hyperins). This risk factor is still not sufficently sought in the general population and, consequently, is not treated promptly, as it should be, to avoid its negative impact on the cardiovascular system. IR's prevalence is constantly growing worldwide, and it is estimated to have reached a prevalence of 51% of the general population in developed and developing countries, and Hyperins is a constant and strong feature of IR. This article aims to stimulate the scientific community towards IR/Hyperins as relevant cardiovascular risk factor, since it is still neglected. The scientific literature analyzed and used to for this article was found on PubMed, Scopus, Science Direct, etc, using the following keywords: insulin, insulin signaling, insulin resistance, hyperinsulinemia, cardiovascular risk factors, cardiovascular system, cardiovascular diseases. We selected studies that explored the association between IR/Hyperins and the cardiovascular system, and those that discussed the possibilities of screening and treatment of IR/Hyperins

Long term combination treatment for severe idiopathic pulmonary arterial hypertension

We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021

Background: This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments Material/Methods: The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. Results: Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (&lt;72 h from onset of symptoms), and group 2 (n=73) was treated &gt;72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P&lt;0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P&lt;0.001). Conclusions: This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization

Efficacy and safety of valsartan plus hydroclorothiazide for high blood pressure

AIM: To evaluate efficacy and tolerability of the combination valsartan plus hydrochlorothiazide (160 mg and 25 mg daily, respectively) in young-middle aged males with high-normal blood pressure (BP) or first-degree arterial hypertension with evidence of target organ damage