Impacto pronóstico de los factores de riesgo cardiovascular en pacientes ingresados por síndrome coronario agudo / Prognostic impact of cardiovascular risk factors in patients admitted for acute coronary syndrome

Introducción y objetivos: Las medidas de prevención cardiovascular hacen hincapié en la importancia del control de factores de riesgo cardiovascular (FRCV). Sin embargo, los estudios más recientes arrojan datos desalentadores cuyo impacto está por determinar. El objetivo de este estudio fue analizar la repercusión que los distintos FRCV y su grado de control tienen sobre el pronóstico de los pacientes tras un síndrome coronario agudo. Pacientes y métodos: Se recogieron datos epidemiológicos, farmacológicos y sobre el control de FRCV de 1.689 pacientes consecutivos que ingresaron durante 2018-2020 por síndrome coronario agudo en un hospital de tercer nivel. Finalmente, se calculó la tasa de eventos adversos cardiovasculares mayores. Resultados: Los pacientes que ingresaron por síndrome coronario agudo fueron predominantemente hombres, con índice de masa corporal>25kg/m2, fumadores (o exfumadores) y con un deficiente control de FRCV (50% para hipertensión y diabetes, y 35% en dislipidemia), especialmente aquellos pacientes con antecedentes personales de cardiopatía isquémica. Se encontró una infrautilización de fármacos útiles para dicho control. Se observó una relación directamente proporcional entre el número de FRCV (o su mal control) con la incidencia de eventos adversos cardiovasculares mayores a 2 años, siendo la hipertensión el factor con mayor repercusión cardiovascular. El confinamiento por SARS-CoV-2 empeoró el grado de control de FRCV y el pronóstico cardiovascular. Conclusión: Hay un importante margen de mejora en el control de los FRCV, que se traduciría en un beneficio pronóstico de los pacientes con cardiopatía isquémica. Es preciso intensificar las medidas de prevención y promoción de salud cardiovascular. (AU)

Introduction and objectives: Cardiovascular prevention measures place the emphasis on controlling cardiovascular risk factors (CVRF). However, the most recent studies provide disappointing data, the impact of which remains to be determined. The objective of this study was to analyse the impact that the different CVRFs, and their degree of control, have on the prognosis of patients after acute coronary syndrome. Patients and methods: Epidemiological, pharmacological, and CVRF control data were collected from 1,689 consecutive patients admitted from 2018 to 2020 for acute coronary syndrome to a tertiary hospital. Finally, the rate of major adverse cardiovascular events was calculated. Results: The patients admitted for acute coronary syndrome were predominantly men, with body mass index>25Kg/m2, smokers (or former smokers) and with poor CVRF control (50% for hypertension and diabetes and 35% for dyslipidaemia), especially those patients with a personal history of ischaemic heart disease. An underutilisation of useful drugs for CVRF control was found. A directly proportional relationship was observed between the number of CVRFs (or their poor control) and the incidence of major adverse cardiovascular events at 2 years, hypertension being the factor with the greatest cardiovascular impact. The SARS-CoV-2 lockdown worsened the degree of CVRF control and cardiovascular prognosis. Conclusion: There is still room for improvement in the control of CVRF, which would translate into a prognostic benefit for patients with ischaemic heart disease. The implementation of cardiovascular prevention campaigns seems essential. (AU)

[Prognostic impact of cardiovascular risk factors in patients admitted for acute coronary syndrome]. / Impacto pronóstico de los factores de riesgo cardiovascular en pacientes ingresados por síndrome coronario agudo.

INTRODUCTION AND OBJECTIVES: Cardiovascular prevention measures place the emphasis on controlling cardiovascular risk factors (CVRF). However, the most recent studies provide disappointing data, the impact of which remains to be determined. The objective of this study was to analyse the impact that the different CVRFs, and their degree of control, have on the prognosis of patients after acute coronary syndrome. PATIENTS AND METHODS: Epidemiological, pharmacological, and CVRF control data were collected from 1,689 consecutive patients admitted from 2018 to 2020 for acute coronary syndrome to a tertiary hospital. Finally, the rate of major adverse cardiovascular events was calculated. RESULTS: The patients admitted for acute coronary syndrome were predominantly men, with body mass index>25Kg/m2, smokers (or former smokers) and with poor CVRF control (50% for hypertension and diabetes and 35% for dyslipidaemia), especially those patients with a personal history of ischaemic heart disease. An underutilisation of useful drugs for CVRF control was found. A directly proportional relationship was observed between the number of CVRFs (or their poor control) and the incidence of major adverse cardiovascular events at 2 years, hypertension being the factor with the greatest cardiovascular impact. The SARS-CoV-2 lockdown worsened the degree of CVRF control and cardiovascular prognosis. CONCLUSION: There is still room for improvement in the control of CVRF, which would translate into a prognostic benefit for patients with ischaemic heart disease. The implementation of cardiovascular prevention campaigns seems essential.

IGF-1 modulates gene expression of proteins involved in inflammation, cytoskeleton, and liver architecture.

Even though the liver synthesizes most of circulating IGF-1, it lacks its receptor under physiological conditions. However, according to previous studies, a damaged liver expresses the receptor. For this reason, herein, we examine hepatic histology and expression of genes encoding proteins of the cytoskeleton, extracellular matrix, and cell-cell molecules and inflammation-related proteins. A partial IGF-1 deficiency murine model was used to investigate IGF-1's effects on liver by comparing wild-type controls, heterozygous igf1+/-, and heterozygous mice treated with IGF-1 for 10 days. Histology, microarray for mRNA gene expression, RT-qPCR, and lipid peroxidation were assessed. Microarray analyses revealed significant underexpression of igf1 in heterozygous mice compared to control mice, restoring normal liver expression after treatment, which then normalized its circulating levels. IGF-1 receptor mRNA was overexpressed in Hz mice liver, while treated mice displayed a similar expression to that of the controls. Heterozygous mice showed overexpression of several genes encoding proteins related to inflammatory and acute-phase proteins and underexpression or overexpression of genes which coded for extracellular matrix, cytoskeleton, and cell junction components. Histology revealed an altered hepatic architecture. In addition, liver oxidative damage was found increased in the heterozygous group. The mere IGF-1 partial deficiency is associated with relevant alterations of the hepatic architecture and expression of genes involved in cytoskeleton, hepatocyte polarity, cell junctions, and extracellular matrix proteins. Moreover, it induces hepatic expression of the IGF-1 receptor and elevated acute-phase and inflammation mediators, which all resulted in liver oxidative damage.

Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases.

This review resumes the association between mitochondrial function and diseases, especially neurodegenerative diseases. Additionally, it summarizes the major role of IGF-1 as a mitochondrial protector, as studied in several experimental models (cirrhosis, aging …). The contribution of mitochondrial dysfunction to impairments in insulin metabolic signaling is also suggested by gene array analysis showing that reductions in gene expression, that regulates mitochondrial ATP production, are associated with insulin resistance and type 2 diabetes mellitus. Moreover, reductions in oxidative capacity of mitochondrial electron transport chain are manifested in obese, insulin-resistant and diabetic patients. Genetic and environmental factors, oxidative stress, and alterations in mitochondrial biogenesis can adversely affect mitochondrial function, leading to insulin resistance and several pathological conditions, such as type 2 diabetes. Finally, it remains essential to know the exact mechanisms involved in mitochondrial generation and metabolism, mitophagy, apoptosis, and oxidative stress to establish new targets in order to develop potentially effective therapies. One of the newest targets to recover mitochondrial dysfunction could be the administration of IGF-1 at low doses. In the last years, it has been observed that IGF-1 therapy has several beneficial effects: restores physiological IGF-1 levels; improves insulin resistance and lipid metabolism; exerts mitochondrial protection; and has hepatoprotective, neuroprotective, antioxidant and antifibrogenic effects. In consequence, treatment of mitochondrial dysfunctions with low doses of IGF-1 could be a powerful and useful effective therapy to restore normal mitochondrial functions.

Altered liver expression of genes involved in lipid and glucose metabolism in mice with partial IGF-1 deficiency: an experimental approach to metabolic syndrome.

BACKGROUND: Insulin growth factor 1 (IGF-1) has multiple effects on metabolism. Much evidence suggests that the deficiency of this hormone increases insulin resistance, impairs lipid metabolism, augments oxidative damage and deregulates the neuro-hormonal axis. An inverse relationship between IGF-1 levels and the prevalence of Metabolic Syndrome (MetS) with its cardiovascular complications has been identified. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. In order to elucidate such mechanisms, the aim of this work was to study, in mice with partial IGF-1 deficiency, liver expression of genes involved in glucose and lipid metabolism as well as serum levels of glucose, triglycerides and cholesterol, as well as liver malondialdehyde (MDA) levels, as a marker for oxidative damage. METHODS: Three experimental groups were studied in parallel: Controls (CO), wild type mice (igf-1 (+/+)); untreated heterozygous mice (Hz, igf-1 (+/-)) and Hz (igf-1 (+/-)) mice treated with low doses of IGF-1 for 10 days (Hz + IGF-1). RESULTS: A reduction of IGF-1 serum levels in the Hz group was found, which was normalized by IGF-1 therapy. Serum levels of glucose, triglycerides and cholesterol were significantly increased in the untreated Hz group as compared to both controls and Hz + IGF-1 groups. The expression of genes involved in gluconeogenesis, glycogenolysis, lipid synthesis and transport, and catabolism were altered in untreated Hz animals and the expression of most of them was normalized by IGF-1 therapy; MDA was also significantly increased in the Hz untreated group. CONCLUSIONS: The mere partial IGF-1 deficiency is responsible for the reduction in the expression of genes involved in glucose and lipid metabolism, resulting in dyslipidemia and hyperglycemia. Such genetic alterations may seriously contribute to the establishment of MetS.

An experimental model of partial insulin-like growth factor-1 deficiency in mice.

Insulin-like growth factor-1 (IGF-1) is responsible for many systemic growth hormone (GH) functions although it has an extensive number of inherent activities (anabolic, cytoprotective, and anti-inflammatory). The potential options for IGF-1 therapy arise as a promising strategy in a wide list of human diseases. However, deeper studies are needed from a suitable animal model. All human conditions of IGF-1 deficiency consist in partially decreased IGF-1 levels since total absence of this hormone is hardly compatible with life. The aim of this work was to confirm that heterozygous Igf-1 (+/-) mice (Hz) may be considered as an appropriate animal model to study conditions of IGF-1 deficiency, focusing on early ages. Heterozygous Igf-1 (+/-) mice were compared to homozygous Igf-1 (+/+) by assessing gene expression by quantitative PCR, serum circulating levels by ELISA, and tissue staining. Compared to controls, Hz mice (25 days old) showed a partial but significant reduction of IGF-1 circulating levels, correlating with a reduced body weight and diminished serum IGFBP-3 levels. Hz mice presented a significant decrease of IGF-1 gene expression in related organs (liver, bone, testicles, and brain) while IGF-1 receptor showed a normal expression. However, gene expression of growth hormone receptor (GHR) was increased in the liver but reduced in the bone, testicles, and brain. In addition, a significant reduction of cortical bone thickness and histopathological alterations in the testicles were found in Hz mice when compared to controls. Finally, the lifelong evolution of IGF-1 serum levels showed significant differences throughout life until aging in mice. Results in this paper provide evidence for considering heterozygous mice as a suitable experimental model, from early stages, to get more insight into the mechanisms of the beneficial actions induced by IGF-1 replacement therapy.