Associations of plasma lipids, lipoproteins, and cardiovascular outcomes with climatic variations in a large Brazilian population of Campinas, São Paulo state: an eight-year study

In this eight-year retrospective study, we evaluated the associations between climatic variations and the biological rhythms in plasma lipids and lipoproteins in a large population of Campinas, São Paulo state, Brazil, as well as temporal changes of outcomes of cardiovascular hospitalizations. Climatic variables were obtained at the Center for Meteorological and Climatic Research Applied to Agriculture (University of Campinas - Unicamp, Brazil). The plasma lipid databases surveyed were from 27,543 individuals who had their lipid profiles assessed at the state university referral hospital in Campinas (Unicamp). The frequency of hospitalizations was obtained from the Brazilian Public Health database (DATASUS). Temporal statistical analyses were performed using the methods Cosinor or Friedman (ARIMA) and the temporal series were compared by cross-correlation functions. In normolipidemic cases (n=11,892), significantly different rhythmicity was observed in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (C) both higher in winter and lower in summer. Dyslipidemia (n=15,651) increased the number and amplitude of lipid rhythms: LDL-C and HDL-C were higher in winter and lower in summer, and the opposite occurred with triglycerides. The number of hospitalizations showed maximum and minimum frequencies in winter and in summer, respectively. A coincident rhythmicity was observed of lower temperature and humidity rates with higher plasma LDL-C, and their temporal series were inversely cross-correlated. This study shows for the first time that variations of temperature, humidity, and daylight length were strongly associated with LDL-C and HDL-C seasonality, but moderately to lowly associated with rhythmicity of atherosclerotic outcomes. It also indicates unfavorable cardiovascular-related changes during wintertime.

Early Carotid Atherosclerosis and Hepatic Lipase-514 C/T Polymorphism: A Study in Hyperalphalipoproteinemic Individuals / Aterosclerosis carotídea subclínica y el polimorfsmo HL-514 C/T de la lipasa hepática: un estudio en individuos hiperalfalipoproteinémicos

Objective: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport and atherosclerosis. The aim of this study was to evaluate the effects of HL -514C/T polymorphism on sub-clinical and established carotid atherosclerotic in hyperalphalipoproteinemic and control individuals. Methods: One hundred and sixty nine asymptomatic individuals (aged 47 ± 16 years), 71 hyperalphalipopro-teinemic (Hyper-A, HDL-C = 68mg/dL) and 98 controls (CTL, HDL-C< 68mg/dL) were selected by clinical and laboratory evaluations. Lipids and lipoproteins were measured by enzymatic methods. HL activity was measured in post-heparin plasma by a radiometric assay and HL-514C/T genotypes were analyzed by PCR. Carotid intima-media thickness (cIMT) was measured by Doppler ultrasonography. Results: No differences in HL -514C/T genotype frequencies were observed between the groups. HL -514C/T polymorphism did not contribute to variations in cIMT or atherosclerotic lesion frequencies in Hyper-A and controls. Furthermore, no interactions between HL-514C/T polymorphism and cIMT or atherosclerotic lesions were found. Conclusions: In hyperalphalipoproteinemic individuals the -514C/T polymorphism is not associated with significant variations in HDL-Cholesterol concentrations. Besides, it has no repercussions on carotid atherosclerosis, although hepatic lipase activity is significantly reduced. No financial conflicts of interest exist.

Objetivo: La Lipasa Hepática (HL) está implicada en el metabolismo de las lipoproteínas distintas y desempeña un papel en el transporte inverso del colesterol y la aterosclerosis. El objetivo de este estudio fue evaluar los efectos del polimorfismo HL-514 C/T en la aterosclerosis carotídea subclínica en los individuos e hiperalfalipoproteinémicos y controles establecidos. Métodos: Ciento sesenta y nueve sujetos asintomáticos (edad 47 ± 16 años), 71 hiperalfalipoproteinémicos (Hyper-A, HDL-C = 68mg/dL) y 98 controles (CTL, HDL-C <68mg/dL) fueron seleccionados por evaluaciones clínicas y de laboratorio. Lípidos y lipoproteínas se midieron por métodos enzimáticos. La actividad de la HL se midió en plasma después de la heparina por el método radiométrico, y los genotipos HL-514C/T se analizaron por PCR. El Grosor íntimo-medial carotídeo (cIMT) se midió mediante ecografía. Resultados: No hubo diferencias en las frecuencias de los genotipos HL-514 C/T se observó entre los grupos. Polimorfismo HL-514 C/T no ha contribuido a los cambios en cIMT o la frecuencia de las lesiones ateroscleróticas en Hyper-A y los controles. Por otra parte, no hay interacción entre el polimorfismo HL-514 C/T y cIMT ni fueron halladas lesiones ateroscleróticas. Conclusiones: El polimorfismo HL -514 C/T no está asociado con cambios significativos en el colesterol HDL en hiperalfalipoproteinémicos particulares y no tiene efecto en la arteriosclerosis carotídea a pesar de que la actividad de la HL ha sido reducida significativamente. Los autores declaran no poseer conflictos de interés.

Association of postalimentary lipemia with atherosclerotic manifestations

We identified different lipemic and metabolic responses after the ingestion of a standardized meal by healthy adults and related them to atherosclerotic markers. Samples from 60 normolipidemic adults were collected before and after a liquid meal (40 g fat/m² body surface) at 0, 2, 4, 6, and 8 h for measurements of lipids, free fatty acids (FFA), insulin, cholesteryl ester transfer protein (CETP), autoantibodies to epitopes of oxidized LDL (oxLDL Ab), lipolytic activities, and apolipoprotein E polymorphism. Mean carotid intima-media thickness (cIMT) was determined by Doppler ultrasound. The volunteers were classified into early (N = 39) and late (N = 31) triacylglycerol (TAG) responders to the test meal. Late responders showed lower HDL cholesterol concentration at fasting and in the TAG peak, lower insulin and higher FFA concentrations compared to early responders. Multivariate regression analyses showed that mean cIMT was associated with gender (male) and age in early responders and by cholesterol levels at the 6th hour in late responders. oxLDL Ab were explained by lipoprotein lipase and negatively by hepatic lipase and oxLDL Ab (fasting period) by CETP (negative) and FFA (positive). This study is the first to identify a postalimentary insulin resistance state, combined with a reduced CETP response exclusively among late responders, and the identification of the regulators of postalimentary atherogenicity. Further research is required to determine the metabolic mechanisms described in the different postalimentary phenotypes observed in this study, as well as in different pathological states, as currently investigated in our laboratory.

Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation

The metabolic effects of carbohydrate supplementation in mice have not been extensively studied. In rats, glucose- and fructose-rich diets induce hypertriacylglycerolemia. In the present study, we compared the metabolic responses to two monosaccharide supplementations in two murine models. Adult male Wistar rats (N = 80) and C57BL/6 mice (N = 60), after 3 weeks on a standardized diet, were submitted to dietary supplementation by gavage with glucose (G) or fructose (F) solutions (500 g/L), 8 g/kg body weight for 21 days. Glycemia was significantly higher in rats after fructose treatment (F: 7.9 vs 9.3 mM) and in mice (G: 6.5 vs 10 and F: 6.6 vs 8.9 mM) after both carbohydrate treatments. Triacylglycerolemia increased significantly 1.5 times in rats after G or F supplementation. Total cholesterol did not change with G treatment in rats, but did decrease after F supplementation (1.5 vs 1.4 mM, P < 0.05). Both supplementations in rats induced insulin resistance, as suggested by the higher Homeostasis Model Assessment Index. In contrast, mice showed significant decreases in triacylglycerol (G: 1.8 vs 1.4 and F: 1.9 vs 1.4 mM, P < 0.01) and total cholesterol levels (G and F: 2.7 vs 2.5 mM, P < 0.05) after both monosaccharide supplementations. Wistar rats and C57BL/6 mice, although belonging to the same family (Muridae), presented opposite responses to glucose and fructose supplementation regarding serum triacylglycerol, free fatty acids, and insulin levels after monosaccharide treatment. Thus, while Wistar rats developed features of plurimetabolic syndrome, C57BL/6 mice presented changes in serum biochemical profile considered to be healthier for the cardiovascular system.

Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes

We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios.