ABSTRACT
OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Amlodipine/administration & dosage , Cell-Derived Microparticles/drug effects , Rosuvastatin Calcium/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/drug therapy , Antihypertensive Agents/administration & dosage , Prospective Studies , Drug Therapy, Combination , Flow Cytometry , Valsartan/administration & dosageABSTRACT
Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.
Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.