Effects of smoking on serum lipid and lipoprotein concen-trations and lecithin:cholesterol acyltransferase activity

Cigarette smoking is one of the major risk factors for cardiovascular disease.The mechanism responsible for this association is still unknown. We measured the activity of lecithin:cholesterol acyltransferase (LCAT), a key factor in the esterification of plasma cholesterol and reverse cholesterol transport, and the levels of lipids and apolipoproteins in the serum of 27 cigarette smoking and 31 non-smoking (control) men. We could not find any significant difference among these parameters between the groups. Serum LCAT activity was lower in smokers, but the difference was statistically nonsignificant. We also classified the two groups in respect to their serum lipid levels as hyper- and normolipidemic, we observed that normolipidemic-smokers had lower (p<0.05) high density lipoprotein-cholesterol (HDL-C) and HDL-ester cholesterol levels compared to the normolipidemic-nonsmokers. While there were no any significant differences between hyperlipidemic-smokers and nonsmokers with respect to any of the parameters. In the end we have got the idea that smoking seems to affect HDL-C and HDL-ester cholesterol levels in the normolipidemic-smokers group, only, Also, LCAT activity tended to be lower in smokers compared to nonsmokers

Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes

Background. Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. Materials and methods. The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides < 2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. Results. No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (R(s) = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (R(s) = -0.48, P < 0.05) and the HDL triglyceride content was positively (R(s) = 0.64, P < 0.01) correlated with CET. Conclusion. Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting-that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus

Modification of human high density lipoprotein by cigarette smoke extract and its impact on reverse cholesterol transport

High density lipoprotein (HDL) normally functions with lecithin:cholesterol acyltransferase (LCAT) to facilitate reverse cholesterol transport whereby excess cholesterol is removed from peripheral tissue sites, such as arteries. Cigarette smoke contains reactive chemicals which may modify HDL and, therefore, impair its antiatherogenic function in reverse cholesterol transport. We tested this hypothesis by first comparing modification of HDL by cigarette smoke extract (CSE) and acrolein, a potent reactive aldehyde known to be present in cigarette smoke. Both CSE and acrolein caused structural modification of HDL in a concentration-dependent manner, as evidenced by diminution of free amino groups, increase in electrophoretic mobility, and apolipoprotein crosslinking. We then evaluated the capacity of modified HDL to activate LCAT, which requires apolipoprotein A-1 as a cofactor, and also to stimulate cholesterol efflux from THP-1 monocytic cells

Crosstalk between high-density lipoproteins and endothelial cells in health and disease: Insights into sex-dependent modulation

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Intense research in vascular biology has advanced our knowledge of molecular mechanisms of its onset and progression until complications; however, several aspects of the patho-physiology of atherosclerosis remain to be further elucidated. Endothelial cell homeostasis is fundamental to prevent atherosclerosis as the appearance of endothelial cell dysfunction is considered the first pro-atherosclerotic vascular modification. Physiologically, high density lipoproteins (HDLs) exert protective actions for vessels and in particular for ECs. Indeed, HDLs promote endothelial-dependent vasorelaxation, contribute to the regulation of vascular lipid metabolism, and have immune-modulatory, anti-inflammatory and anti-oxidative properties. Sex- and gender-dependent differences are increasingly recognized as important, although not fully elucidated, factors in cardiovascular health and disease patho-physiology. In this review, we highlight the importance of sex hormones and sex-specific gene expression in the regulation of HDL and EC cross-talk and their contribution to cardiovascular disease

The cardiovascular effects of chronic hypoestrogenism in amenorrhoeic athletes: a critical review.

In premenopausal women, the most severe menstrual dysfunction is amenorrhoea, which is associated with chronic hypoestrogenism. In postmenopausal women, hypoestrogenism is associated with a number of clinical sequelae related to cardiovascular health. A cardioprotective effect of endogenous oestrogen is widely supported, yet recent studies demonstrate a deleterious effect of hormone replacement therapy for cardiovascular health. What remain less clear are the implications of persistently low oestrogen levels in much younger amenorrhoeic athletes. The incidence of amenorrhoea among athletes is much greater than that observed among sedentary women. Recent data in amenorrhoeic athletes demonstrate impaired endothelial function, elevated low- and high-density lipoprotein levels, reduced circulating nitrates and nitrites, and increased susceptibility to lipid peroxidation. Predictive serum markers of cardiovascular health, such as homocysteine and C-reactive protein, have not yet been assessed in amenorrhoeic athletes, but are reportedly elevated in postmenopausal women. The independent and combined effects of chronic hypoestrogenism and exercise, together with subclinical dietary behaviours typically observed in amenorrhoeic athletes, warrants closer examination. Although no longitudinal studies exist, the altered vascular health outcomes reported in amenorrhoeic athletes are suggestive of increased risk for premature cardiovascular disease. Future research should focus on the presentation and progression of these adverse cardiovascular parameters in physically active women and athletes with hypoestrogenism to determine their effects on long-term health

Smoking cessation, alcohol intake and transient increase in the risk of metabolic syndrome among Japanese smokers at one health checkup institution

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is potentially effective measures to identify individuals at risk of coronary heart disease (CHD) and type 2 diabetes. To verify the hypothesis that smoking cessation may increase the risk of MetS, a follow-up study taking drinking habit into account was conducted for the examinees at one health checkup institution.</p> <p>Methods</p> <p>Subjects were the examinees who visited the Institution for Disease Prevention and Health Checkup, Seirei Mikatabara Hospital for annual health checkup from January 2003 to December 2006. Among them, 5,872 smokers (5,479 men, 93.3%) free from MetS at the first year in two consecutive years were selected. For the long term follow-up, the risk of MetS among those who maintained their nonsmoking status for 1 or 2 additional years was evaluated.</p> <p>Results</p> <p>Relative to non-quitters, quitters showed a significantly elevated adjusted hazard ratio (aHR) of MetS in two consecutive years (aHR = 2.09, 95% confidence interval: 1.43–3.04, <it>P </it>< 0.001). The aHR was higher among the quitters who had a drinking habit at the first year (aHR = 2.42, 95% CI: 1.48–3.94, <it>P </it>< 0.001). Analyses for 1 or 2 additional years of follow-up revealed that this significant increase in risk of MetS was transient.</p> <p>Conclusion</p> <p>The present study revealed that smoking cessation elevated the risk of MetS significantly, especially among drinkers. Although this detrimental effect of smoking cessation was found to be during only a short term, our results suggested that we should take measures, presumably including interventions for alcohol cessation, not to expose smoking quitters to this adverse effect. Further investigations are required to confirm our findings.</p

Dyslipidemia

Dyslipidemia has a complex pathophysiology consisting of various genetic, lifestyle, and environmental factors. It has many adverse health impacts, notably in the development of chronic non-communicable diseases. Significant ethnic differences exist due to the prevalence and types of lipid disorders. While elevated serum total- and LDL-cholesterol are the main concern in Western populations, in other countries hypertriglyceridemia and low HDL-cholesterol are more prevalent. The latter types of lipid disorders are considered as components of the metabolic syndrome. The escalating trend of obesity, as well as changes in lifestyle and environmental factors will make dyslipidemia a global medical and public health threat, not only for adults but for the pediatric age group as well. Several experimental and clinical studies are still being conducted regarding the underlying mechanisms and treatment of dyslipidemia. The current book is providing a general overview of dyslipidemia from diverse aspects of pathophysiology, ethnic differences, prevention, health hazards, and treatment

Coronary heart disease risk : family history and gene-environment interaction

The first part of this thesis describes research into lifestyle, genetic, and biological factors that may underlie the increased risk for coronary heart disease (CHD) in individuals with a family history of this disorder. The second part of this thesis describes whether levels of plasma lipids and lipoproteins - which are among the major CHD risk factors - are influenced by the interaction between common gene polymorphisms and lifestyle-related factors. A large cohort study was used to evaluate the association between family history and CHD mortality. The association of a family history with gene polymorphisms, lifestyle-related and biological CHD risk factors, as well as gene-environment interactions were studied cross-sectionally. For this purpose subsamples from a large population-based project (the Cardiovascular Disease Risk Factor Monitoring Project) and the European Atherosclerosis Research Study (EARS) were used.Family history increased the risk for CHD death in men and women. Only a small part was mediated through known CHD risk factors. The most pronounced characteristics of individuals with a family history were the higher levels of total cholesterol and apolipoprotein (apo) B as compared to subjects without a family history. The contribution of lifestyle-related (i.e. modifiable) factors to higher apo B levels in individuals with a family history was small; most of it seemed to be genetically determined. The apo E polymorphism is probably one of the most important genetic factors involved. Besides the apo E4 isoform, the D9N mutation and the N291S mutation in lipoprotein lipase (LPL) were more frequent among subjects with a parental history of premature myocardial infarction. Other gene polymorphisms (LPL S447X, CETP TaqIB and apo CIII SstI) proved to be non-informative.Like family history, genotypes can not be modified. However, the effect of some polymorphisms clearly depended on lifestyle-related factors. A significant interaction between the apo E2 isoform and body mass index was found in EARS as well as in the population-based sample of Dutch origin. Surprisingly, in EARS the association between BMI and apo B levels was more pronounced in E2-carriers compared to subjects with other phenotypes, while in the Dutch sample the association was weaker in apo E2-carriers. Further, a strong interaction between the LPL D9N mutation and physical activity became apparent. Physically inactive carriers of the mutation (n=5) had considerably higher total cholesterol and apo B levels compared to non-carriers, whereas their HDL-cholesterol concentrations were lower. This was not the case for physically active carriers of this mutation (n=10). Our studies also showed that only among moderate alcohol consumers, subjects with the CETP B2B2 genotype presented with higher mean HDL-cholesterol levels compared to subjects with other genotypes. Furthermore, smokers with the apo CIII S1S2 genotype had higher levels of triglycerides and apo B and somewhat lower levels of HDL-cholesterol, compared to smokers with the S1S1 genotype. This was not observed among non-smokers.It is concluded that the underlying mechanisms for the increased risk in individuals with a family history of CHD remain unclear. The risk of CHD is highest in individuals with a family history and unfavorable levels of other CHD risk factors. Therefore, assessing family history is important for risk prediction and prevention, despite the fact that family history by itself cannot be changed. Since little is known about the most useful definition of a family history more large long-term prospective studies are needed. Furthermore, gene-environment interaction implies that a genetic predisposition to unfavorable lipid levels and consequently CHD risk is not in all cases something of which the consequences cannot be influenced. However, our insights into specific gene-environment interactions is limited. More research is needed before our knowledge about gene-environment interactions can be applied for better focusing preventive measures to subgroups in the population that are susceptible to CHD.</p

Exposure to Tobacco Smoke and Markers of Subclinical Atherosclerosis in Children and Adolescents. The STRIP Study.

Background: Measurement of serum cotinine, a major metabolite of nicotine, provides a valid marker for quantifying exposure to tobacco smoke. Exposure to tobacco smoke causes vascular damage by multiple mechanisms, and it has been acknowledged as a risk factor for atherosclerosis. Multifactorial atherosclerosis begins in childhood, but the relationship between exposure to tobacco smoke and arterial changes related to early atherosclerosis have not been studied in children. Aims: The aim of the present study was to evaluate exposure to tobacco smoke with a biomarker, serum cotinine concentration, and its associations with markers of subclinical atherosclerosis and lipid profile in school-aged children and adolescents. Subjects and Methods: Serum cotinine concentration was measured using a gas chromatographic method annually between the ages 8 and 13 years in 538-625 children participating since infancy in a randomized, prospective atherosclerosis prevention trial STRIP (Special Turku coronary Risk factor Intervention Project). Conventional atherosclerosis risk factors were measured repeatedly. Vascular ultrasound studies were performed among 402 healthy 11-year-old children and among 494 adolescents aged 13 years. Results: According to serum cotinine measurements, a notable number of the school aged children and adolescents were exposed to tobacco smoke, but the exposure levels were only moderate. Exposure to tobacco smoke was associated with decreased endothelial function as measured with flow-mediated dilation of the brachial artery, decreased elasticity of the aorta, and increased carotid and aortic intima-media thickness. Longitudinal exposure to tobacco smoke was also related with increased apolipoprotein B and triglyceride levels in 13-year-old adolescents, whose body mass index and nutrient intakes did not differ. Conclusions: These findings suggest that exposure to tobacco smoke in childhood may play a significant role in the development of early atherosclerosis. Key Words: arterial elasticity, atherosclerosis, children, cotinine, endothelial function, environmental tobacco smoke, intima-media thickness, risk factors, ultrasoundSiirretty Doriast