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J Cardiovasc Med (Hagerstown) ; 23(2): 91-97, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34690259

RESUMO

AIM: Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab. RESULTS: Total cholesterol significantly decreased progressively until the fourth year; after 4 years there was a significant reduction (-125.5 mg/dl, -51.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -2.8 mg/dl (-2.3%) compared with the third year. Low-density lipoprotein-cholesterol (LDL-C) also decreased significantly until the fourth year. After 3 years, there was a significant reduction (-117.8 mg/dl, -71.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year) and -13.9 mg/dl (-22.8%) compared with the second year; after 4 years there was a significant reduction (-121.4 mg/dl, -73.7%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -3.6 mg/dl (-7.7%) compared with the third year. High-density lipoprotein-cholesterol increased significantly only during the fourth year of detection. After 3 years, there was a nonsignificant increase (4.9 mg/dl, 10.0%, P = 0.061 vs baseline) and 1.6 mg/dl (3.1%) compared with the second year; after 4 years, there was a significant increase (5.2 mg/dl, 10.6%, P < 0.05 vs baseline) and 0.3 mg/dl (0.6%) compared with the third year. The value of Tg was significantly reduced progressively until the second year and then stabilized in the third and fourth years. After 3 years, the value of Tg stabilized (-48.6 mg/dl, -32.4%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) and -4.8 mg/dl (-4.5%) compared with the second year; after 4 years (-46.4 mg/dl, -31.0%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) there was a slight and nonsignificant increase of 2.2 mg/dl (2.2%) compared with the third year. Regarding adverse events, both drugs were well tolerated. CONCLUSIONS: We showed that PCSK9 inhibitors are well tolerated and provide long-term significant LDL-C lowering in individuals with hyperlipidemia.


Assuntos
Dislipidemias/tratamento farmacológico , Inibidores de PCSK9/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Atherosclerosis ; 189(2): 401-7, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16442116

RESUMO

The aim of this study was to compare the use of several biomarkers to identify obese children and adolescents with increased metabolic risk. One hundred sixty-two Caucasian obese children and adolescents (41% males, 9-18 years old) referred to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP), fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of obese children had the MS defined using World Health Organization-derived child specific criteria. MS subjects had significantly lower AD (p<0.01) and higher log-PAI-1 (p<0.001), uric acid (p<0.0001), and IL-18 (p<0.001). Subjects with AD levels

Assuntos
Adiponectina/sangue , Síndrome Metabólica/sangue , Obesidade/complicações , Adolescente , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Criança , Feminino , Humanos , Insulina/sangue , Interleucina-8/sangue , Itália/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Obesidade/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Ácido Úrico/sangue
4.
Obesity (Silver Spring) ; 19(8): 1684-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21273999

RESUMO

We assessed (i) the association between early arterial disease and factors linked to adiposity, dietary habits, and family in a young cohort of 151 obese children and adolescents with less than or equal to one cardiovascular (CV) risk factor, (ii) whether in subjects with carotid calcifications there was an imbalance of calcium-phosphorus homeostasis. Measurement included: carotid ultrasound, oral glucose tolerance test, anthropometry, body composition, dietary history, white blood cells count, lipids, uric acid, adiponectin, insulin, C-reactive protein, plasminogen activator inhibitor 1 (PAI-1), 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium and phosphorus. Obese children with carotid artery intima media thickness (cIMT) values >75° percentile (0.55 mm), compared to those with lower cIMT, were more obese, more often pubertal and had higher prevalence of family history of CV disease (CVD) (P < 0.05), higher plasma PAI-1 and uric acid (P < 0.001) and lower adiponectin (P < 0.05) and high-density lipoprotein (HDL) cholesterol levels (P < 0.05). After adjustment for sex, age, puberty, obesity, and insulin levels, only PAI-I remained significantly different between the two groups (10.9 (7.2-29.8) vs. 6.2 (4.3-10.6) ng/ml, P < 0.001). Dietary intake did not affect cIMT values. Eight percent of subjects showed nonatherosclerotic carotid calcifications with patchy pattern. These children had a worse lipid profile (P < 0.05) and higher plasma PTH levels (48.6 ± 21.5 vs 38.5 ± 16.9 pg/ml, P < 0.05) that were inversely associated with 25-hydroxyvitamin D levels (r = 0.245, P < 0.01). Present results suggest that (i) several adiposity-related factors may play a role in promoting the development of early arterial diseases in young subjects with a benign phenotype of obesity, (ii) a PTH rise resulting from a subclinical imbalance in calcium-phosphorus homeostasis may affect the biological process of vascular calcifications.


Assuntos
Aterosclerose/etiologia , Cálcio/metabolismo , Obesidade/complicações , Inibidor 1 de Ativador de Plasminogênio/sangue , Túnica Íntima/patologia , Adiponectina/sangue , Adolescente , Aterosclerose/sangue , Aterosclerose/patologia , Biomarcadores , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Criança , HDL-Colesterol/sangue , Família , Feminino , Humanos , Masculino , Obesidade/sangue , Obesidade/patologia , Hormônio Paratireóideo/sangue , Fenótipo , Fósforo/metabolismo , Puberdade , Fatores de Risco , Túnica Íntima/metabolismo , Ácido Úrico/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
5.
Obes Facts ; 4(1): 27-33, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21372608

RESUMO

OBJECTIVE: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin. METHODS: For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups. RESULTS: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group. CONCLUSION: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Obesidade/metabolismo , Tecido Adiposo/efeitos dos fármacos , Adulto , Células Cultivadas , Feminino , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Estilo de Vida , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo
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