Dominik Grathwohl

Structural, Functional, and Hemodynamic Changes of the Common Carotid Artery With Age in Male Subjects

Aging of the common carotid artery (CCA) is associated with different principal structural, functional, and hemodynamic changes, which are often influenced by several atherosclerotic risk factors, so that it is difficult to estimate the exclusive effect of aging on this process. Studies dealing with vascular aging of the CCA usually assess only single, dimensional, or functional parameters, although it is likely that there are interactions and probably differences between them. Moreover, regional vascular blood flow characteristics are often not taken into consideration. Therefore, the aim of the study was to assess the age-related multiparametric changes of the CCA properties with ultrasound in 69 male subjects between the ages of 16 and 75 (42.4+/-16.5 years), who were screened for the absence of major atherosclerotic risk factors or existing vascular disease. As a result, the intima media thickness (0.052 mm/10 y) and diastolic diameter (0.17 mm/10 y) increased nearly linearly with age (r=0.60, P<0.001; and r=0.46, P<0.001, respectively). The absolute diastolic/systolic diameter change diminished by 0.10 mm/10 y (r=-0. 73, P<0.001) and peak expansion velocity dropped by 0.12 cm/s per 10 years (r=-0.62, P<0.001) highly significantly with age. The peak blood flow velocity decreased continuously with age (r=-0.67, P<0. 00) by 9.3 cm/s per 10 years. According to multiple regression analysis, peak blood flow velocity seems to reflect the changes of several structural and functional parameters in one; intima-media thickness was determined by diastolic arterial diameter and age as independent variables. The data indicate that a multiparametric assessment may contribute to a better understanding of vascular aging and might be the basis for further studies to evaluate the association of atherosclerotic risk factors and/or major vascular disease with local changes in the CCA.

Influence of 4 weeks' intervention by exercise and diet on low-density lipoprotein subfractions in obese men with type 2 diabetes

Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non-insulin-dependent diabetes (age, 49 +/- 9 years; body mass index [BMI], 33.1 +/- 5.1 kg/m2). Reductions in body weight (P < .001) and improvements in fasting blood glucose, insulin, fructosamine (P < .001), and free fatty acids (P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very-low-density lipoprotein (VLDL) (P < .01), intermediate-density lipoprotein (IDL), and small, dense (>1.040 g/mL) LDL particles (P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.

Assessment of carotid wall motion and stiffness with tissue Doppler imaging.

In this study, the wall motion of the common carotid artery was characterized by measuring wall-motion velocity (Wv) with tissue Doppler imaging (TDI) in 78 male and female subjects (16-75 y) with no history of cardiovascular disease. The near and far arterial wall showed essentially different Wv patterns. To assess the vascular systolic distension, the Wv of the near and far arterial walls were measured and a Wv index was calculated by subtracting the far Wv from the near Wv. Aging was associated with a 2.0-2.5-fold decrease of peak Wv index. Corrected for carotid diameter and blood pressure, the peak Wv index and mean systolic acceleration to the peak Wv correlated highly with arterial distensibility (r = 0.81 resp. r = 0.75) and compliance (r = 0.73 resp. r = 0.68). This study demonstrates the feasibility of TDI in the characterization of wall motion patterns and in the assessment of common carotid artery stiffness.

Concurrent reductions of serum leptin and lipids during weight loss in obese men with type II diabetes

The aim of the study was to examine the effects of weight reduction by exercise and diet on metabolic control in obese subjects with insulin resistance, particularly investigating if changes in serum leptin concentrations were directly associated with improvements in metabolic control. Twenty obese men (48 +/- 8 yr; body mass index 32. 1 +/- 3.9 kg/m(2)) with previously diagnosed type II diabetes mellitus were assigned to a 4-wk intervention program of exercise (2, 200 kcal/wk) and diet (1,000 kcal/day; 50% carbohydrates, 25% protein, 25% fat; polyunsaturated-to-saturated fatty acid ratio 1.0). Intervention induced significant reductions in body weight and serum leptin levels, and improvements in lipoprotein profile and glucose control. Reductions in leptin levels were directly associated with reductions in serum triglycerides and cholesterol, a finding that was independent of improvements in glucose control. These data show that serum leptin concentrations can be reduced with caloric restriction and exercise in male patients with type II diabetes, and they suggest a direct relationship between leptin and lipoprotein metabolism that is not solely due to weight reduction.The aim of the study was to examine the effects of weight reduction by exercise and diet on metabolic control in obese subjects with insulin resistance, particularly investigating if changes in serum leptin concentrations were directly associated with improvements in metabolic control. Twenty obese men (48 ± 8 yr; body mass index 32.1 ± 3.9 kg/m2) with previously diagnosed type II diabetes mellitus were assigned to a 4-wk intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/day; 50% carbohydrates, 25% protein, 25% fat; polyunsaturated-to-saturated fatty acid ratio 1.0). Intervention induced significant reductions in body weight and serum leptin levels, and improvements in lipoprotein profile and glucose control. Reductions in leptin levels were directly associated with reductions in serum triglycerides and cholesterol, a finding that was independent of improvements in glucose control. These data show that serum leptin concentrations can be reduced with caloric restriction and exercise in male patients with type II diabetes, and they suggest a direct relationship between leptin and lipoprotein metabolism that is not solely due to weight reduction.

Crystallization and Preliminary X-Ray Diffraction Data of Two Different Human Low-Density Lipoprotein (LDL) Subfractions

Human LDL subfractions LDL‐2 (d = 1.031–1.034 g/ml) and LDL‐5 (d = 1.040–1.044 g/ml) were crystallized in two different crystal forms by using polyethylene glycol as a precipitant. Both fractions were from one donor. Crystals of LDL‐5 were yellow, hexagonal, and showed no dichroism. Crystals of LDL‐2 were of the same color, had a rodlike shape with notches at both ends, and were highly dichroitic. LDL‐2 crystals diffracted to a resolution of 29 Å by using synchrotron radiation. Indexing in P1 resulted in preliminary parameters for the reduced cell of a = 171 Å, b = 438 Å, c = 519 Å, α = 102°, β = 99°, γ = 91. These dimensions are consistent with the size of LDL particles. Using Fourier transform infrared spectroscopy (FTIR) and agarose gel electrophoresis, we could further confirm that the crystals consist of LDL. The FTIR spectrum showed bands characteristic for lipids and protein. Dissolved crystals exhibited a mobility similar to native LDL in agarose gels and could be stained with anti‐human apolipoprotein B (apoB). Proteins 28:293–297, 1997.

Lipoprotein phenotype and adhesion molecules correlate with diurnal triglyceride profiles in patients with coronary artery disease

BACKGROUND AND AIM To assess the relationships between different diurnal triglyceride (TG) profiles (p) and the atherogenicity of the lipoprotein phenotype and adhesion molecule concentrations in patients with coronary artery disease (CAD). METHODS AND RESULTS Repeated measurements of fasting TG and TGp were made in 29 CAD patients; fasting cholesterol levels (total-C, VLDL, LDL, HDL and small dense LDL) and soluble cell adhesion molecules (sCAM) (ICAM-1 and E-selectin) were measured once. Three different TGps were defined: fasting (137.0 +/- 60.7 mg/dL) and all other TG levels <200 mg/dL (LL; n=7); a fasting TG level <200 mg/dL (147.0 +/- 49.9 mg/dL) and maximum TG levels >200 mg/dL (LH; n=13); and both fasting (225.1+/-76.2 mg/dL) and maximum TG levels >200 mg/dL (HH; n=9). We then analysed the associations between the TGp types and the lipoprotein phenotype and CAMs. LL had significantly lower values than LH (p<0.05 for all parameters except sE-selectin) and HH (p<0.05 for all parameters) of VLDL (11.2 +/- 5.8, 18.8 +/- 9.4, 28.1 +/- 8.8 mg/dL), LDL-5 (11.6 +/- 3.3, 16.4 +/- 4.5, 22.1 +/-7.9 mg/dl) and LDL-6 (12.0 +/- 3.2, 17.0 +/- 5.7, 25.7 +/- 9.6 mg/dL), sICAM-1 (209.4 +/- 30.3, 267.5 +/- 60.6, 273.4 +/- 59.1 ng/dL) and sE-selectin (25.1 +/- 17.6, 35.5 +/- 11.5, 48.5 +/- 20.2 ng/dL). CONCLUSION Although the differences in fasting TG levels between the LL and LH groups were not significantly different, LH had a more atherogenic lipoprotein phenotype and higher concentrations of adhesion molecules. TGp measurements seem to be suitable for identifying CAD patients with an unfavourable diurnal TG and atherosclerosis-prone lipoprotein metabolism.

1.P.2 Crystallization and preliminary X-ray diffraction data of two different human low density lipoprotein (LDL) subfractions

Human LDL subfractions LDL-2 (d = 1.031-1.034 g/ml) and LDL-5 (d = 1.040-1.044 g/ml) were crystallized in two different crystal forms by using polyethylene glycol as a precipitant. Both fractions were from one donor. Crystals of LDL-5 were yellow, hexagonal, and showed no dichroism. Crystals of LDL-2 were of the same color, had a rodlike shape with notches at both ends, and were highly dichroitic. LDL-2 crystals diffracted to a resolution of 29 A by using synchrotron radiation. Indexing in P1 resulted in preliminary parameters for the reduced cell of a = 171 A, b = 438 A, c = 519 A, alpha = 102 degrees, beta = 99 degrees, gamma = 91. These dimensions are consistent with the size of LDL particles. Using Fourier transform infrared spectroscopy (FTIR) and agarose gel electrophoresis, we could further confirm that the crystals consist of LDL. The FTIR spectrum showed bands characteristic for lipids and protein. Dissolved crystals exhibited a mobility similar to native LDL in agarose gels and could be stained with anti-human apolipoprotein B (apoB).