Blood Rheology and the Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio in Dyslipidaemic and Normolipidaemic Subjects

T MACHIDA 1 2 H SUMINO 1 2 M FUKUSHIMA 0 2 N KOTAJIMA 1 2 H AMAGAI 1 2 M MURAKAMI 0 1 2 0 Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine , Gunma, Japan 1 Clinical Laboratory Centre 2 Dr Masami Murakami Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine , 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan - >> Version of Record - Dec 1, 2010 What is This? Downloaded from imr.sagepub.com by guest on October 16, 2014 Blood Rheology and the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio in Dyslipidaemic and Normolipidaemic Subjects The association between blood rheology and the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) was investigated in 142 dyslipidaemic and 253 normolipidaemic subjects. Blood rheology was examined by the microchannel method and fasting serum concentrations of LDL-C, triglyceride and HDL-C were measured. Passage time of whole blood correlated positively with LDL-C concentration, triglyceride concentration and LDL-C/HDL-C ratio, and negatively with HDL-C concentration. Passage time of whole blood was significantly higher in dyslipidaemic and normolipidaemic subjects with LDL-C/HDL-C ratio > 2.0 than in those with ratio < 1.5. Thus, dyslipidaemic subjects had impaired blood rheology, elevated LDL-C and triglyceride concentrations and elevated LDL-C/HDL-C ratio, and reduced HDL-C concentrations. Dyslipidaemic and normolipidaemic subjects with a more elevated LDL-C/HDL-C ratio had greater blood rheology impairment than those with a less elevated ratio. These data suggest that an elevated LDL-C/HDL-C ratio may be helpful in predicting impaired blood rheology. Introduction Epidemiological studies have established dyslipidaemia and dyslipoproteinaemia as important risk factors for coronary heart disease (CHD).1 3 High concentrations of low-density lipoprotein cholesterol (LDL-C) and low concentrations of high-density lipoprotein cholesterol (HDL-C) result in an increased risk of CHD.1 3 Moreover, the LDLC/HDL-C ratio is more important than the individual levels of LDL-C and HDL-C, and is a helpful parameter in predicting atherosclerosis: a high ratio indicates a high risk of clinical events and a low ratio Downloaded from imr.sagep1ub9.co7m 5by guest on October 16, 2014 indicates a low risk.4,5 A desirable LDLC/HDL-C ratio would be < 2.0; in a large clinical study, an LDL-C/HDL-C ratio < 2 during 24 months of treatment with a statin was associated with regression of coronary artery atheroma.6 Thus, the LDL-C/HDL-C ratio is superior to the individual levels of LDL-C and HDL-C in the prediction of elevated CHD risk.4,5 Despite new insights into the pathogenesis of atherosclerosis in recent years, the pathophysiology of the atherosclerotic process is not fully understood. Haemorheological parameters are considered to be related to the formation of atherosclerotic plaques and thrombi because fibrinogen concentration,7,8 plasma viscosity9,10 and blood viscosity11,12 have been identified as independent risk factors for atherosclerosis. Haemorheological parameters are associated with lipid and lipoprotein concentrations; several clinical studies have demonstrated that plasma viscosity correlates positively with total cholesterol, triglyceride and LDL-C concentrations and inversely with HDL-C concentration,13 and that the permeability of erythrocytes correlates negatively with total cholesterol, LDL-C and triglyceride levels.14 A microchannel method of studying blood rheology has made it possible to view blood flow under a microscope connected to a visual display unit while evaluating blood rheology and may be useful in acquiring new insights into the pathophysiology of the atherosclerotic process in dyslipidaemic patients.15 21 Blood rheology measured by the microchannel method has been reported to be influenced by red blood cell deformability, leucocyte adhesiveness, platelet aggregation and whole blood and plasma viscosity.15 21 Using the microchannel method, our research group has previously reported that blood rheology is impaired in hypercholesterolaemic subjects21 and that blood rheology is correlated positively with total cholesterol, triglyceride and LDL-C, and negatively with HDL-C concentrations.17,21 It remains unclear, however, whether the LDL-C/HDL-C ratio is associated with blood rheology. To investigate the association between blood rheology and the LDL-C/HDL-C ratio in dyslipidaemic and normolipidaemic subjects, the present study measured blood rheology and the serum concentrations of LDL-C, triglyceride and HDL-C in dyslipidaemic and normolipidaemic subjects. Subjects and methods SUBJECTS Consecutive male and female Japanese dyslipidaemic and normolipidaemic volunteers were recruited to this study. They comprised staff and students from Gunma University who underwent routine health check at Gunma University Hospital. Dyslipidaemia was defined as an elevated serum LDL-C concentration ( 140 mg/dl), an elevated serum triglyceride concentration ( 150 mg/dl) or a reduced serum HDL-C concentration (< 40 mg/dl), and normolipidaemia was defined as normal serum LDL-C (< 140 mg/dl), normal serum triglyceride (< 150 mg/dl) and normal serum HDL-C ( 40 mg/dl) concentrations, according to the criteria of the Japanese Atherosclerosis Society.22 Exclusion criteria were diabetes mellitus, hypertension, thyroid disease, acute or severe chronic liver disease, coronary artery disease, thromboembolic disease, renal disease and metabolic or other endocrine diseases that could influence lipid metabolism. Body mass index was calculated from subjects weight in kilograms divided by their height in metres squared. All participants were asked to complete a self-administered Downloaded from imr.sagep1ub9.co7m 6by guest on October 16, 2014 questionnaire that included personal characteristics (age, sex, smoking status). Smokers were defined as those subjects who were currently smokers and non-smokers were those who currently did not smoke. Written informed consent was obtained from each participant and the study was approved by the Institutional Review Board of Gunma University Hospital. STUDY PROCEDURE In the morning, after a 12 h fast, anthropometric measurements were made and blood samples were collected into three polypropylene tubes for serum and plasma analyses and for whole blood rheology measurements. Blood samples (2 ml) were obtained by puncture of an antecubital vein using 23 G needles while the subject was in a sitting position. Heparin solution (0.1 ml, 1000 IU/ml) was used as an anticoagulant. Rheology of whole blood samples was measured within 2 h of sample collection. The LDL-C/HDL-C ratio was divided into three categories as described previously:6 those with a ratio < 1.5; those with a ratio 1.5 and 2.0; and those with a ratio > 2.0. This resulted in a total of six groups (...truncated)