Clarifying the Link Between the Blood Lactate Concentration and Cardiovascular Risk.

The blood lactate value at rest (Lacrest) is linked to cardiovascular outcomes. It is unclear whether this association holds true in younger, healthy subjects, especially as the pathophysiological connection between Lacrest and cardiometabolic disease is not well understood. The aim of this study is clarifying the link between Lacrest and cardiovascular risk, and to study explanatory factors for the variance of Lacrest concerning metabolism and physical activity in a population of healthy patient-athletes. The distribution and intra-individual variability of Lacrest was assessed based on 9051 samples. The 10-year cardiovascular risk was then approximated using the Framingham risk score in a group of 1315 samples from patient-athletes. Cross-validated linear regression was used to analyze explanatory variables for Lacrest and 10-year cardiovascular risk. Lacrest is weakly associated with the Framingham score. This association disappears when adjusting for blood lipids. Lacrest is also linked to the predominant type of exercise with endurance athletes featuring a higher Lacrest. Lacrest does not independently predict the estimated cardiovascular risk but is associated with lipid parameters. Moreover, the intra-individual variability of Lacrest is high in a relevant number of subjects, which does not point towards the feasibility to use Lacrest as an individual risk factor.

Phase-contrast MR flow imaging: A tool to determine hepatic hemodynamics in rats with a healthy, fibrotic, or cirrhotic liver.

PURPOSE: To test a magnetic resonance (MR) scanning protocol as a noninvasive tool to determine hepatic hemodynamics and to assess the degree of liver fibrosis in an animal model of liver fibrosis and cirrhosis. MATERIALS AND METHODS: Fifty-four male Wistar rats were studied. Thirty-nine received thioacetamide (TAA) in their drinking water for either 12 or 16 weeks. MR measurements were performed using flow-sensitive 2D phase-contrast MRI and a 9.4T preclinical scanner. The following hemodynamic parameters were investigated: portal cross-sectional area, mean portal flow velocity, and portal and aortic flow volume rate. Therefore, rats (n = 46) were divided into three groups: CON (control, n = 13), FIB (fibrosis, n = 25), and CIR (cirrhosis, n = 8). Furthermore, the degree of liver fibrosis was assessed by a self-established MR score and verified by a standardized histological score (n = 48). RESULTS: Portal and aortic flow parameters could be reliably detected. A significant decrease in portal flow velocity was found in FIB (FIB vs. CON: -21%, P = 0.006 and CIR vs. CON: -17%, P = 0.105) and in portal flow volume rate in FIB and CIR (FIB vs. CON: -20%, P = 0.009 and CIR vs. CON: -25%, P = 0.024). If the histological score is taken as standard, the self-established MR score enabled discrimination between healthy and diseased livers (sensitivity to identify diseased livers: 89% and specificity to identify healthy livers: 100%). CONCLUSION: This MR scanning protocol presents a noninvasive tool to determine hepatic hemodynamics in healthy and diseased rats. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1526-1534.

Introduction of digital speech recognition in a specialised outpatient department: a case study.

BACKGROUND: Speech recognition software might increase productivity in clinical documentation. However, low user satisfaction with speech recognition software has been observed. In this case study, an approach for implementing a speech recognition software package at a university-based outpatient department is presented. METHODS: Methods to create a specific dictionary for the context "sports medicine" and a shared vocabulary learning function are demonstrated. The approach is evaluated for user satisfaction (using a questionnaire before and 10 weeks after software implementation) and its impact on the time until the final medical document was saved into the system. RESULTS: As a result of implementing speech recognition software, the user satisfaction was not remarkably impaired. The median time until the final medical document was saved was reduced from 8 to 4 days. CONCLUSION: In summary, this case study illustrates how speech recognition can be implemented successfully when the user experience is emphasised.

Value of MRI and MRS fat measurements to complement conventional screening methods for childhood obesity.

PURPOSE: To evaluate a protocol combining abdominal fat-water magnetic resonance imaging (MRI) and liver single voxel magnetic resonance spectroscopy (MRS) for studies of childhood obesity. MATERIALS AND METHODS: Six obese male children and five age-matched normal-weight controls underwent abdominal fat-water Dixon MRI based on a gradient echo sequence with multiple echo times and single voxel liver MRS at a field strength of 3T. The MRI/MRS data were compared with data previously acquired from an obese adult cohort and with anthropometric and blood parameters that are typically acquired for screening in childhood obesity. RESULTS: There was a very strong correlation (r = 0.96) between the body mass index standard deviation score (BMI-SDS) and the subcutaneous fat volume fraction in the examined children, but only a moderate correlation (r = 0.62) between the BMI-SDS index and the intraabdominal fat volume fraction, which is much lower in the obese children (5.3 ± 1.1%) than in the obese adult cohort (19.4 ± 2.9%). Furthermore, a significant difference between the two child cohorts was observed in the intrahepatic lipid (IHL) content as obtained with MRS (P = 0.017). However, even the obese child cohort shows an IHL content that is 1-2 orders of magnitude lower (1.0 ± 0.5%) than in the obese adult cohort (17.0 ± 8.7%). CONCLUSION: The proposed method was successfully applied in children and may complement traditional clinical screening methods for childhood obesity such as anthropometry and laboratory tests to better characterize the obesity-associated metabolic risk.

Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial.

Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects. The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia. A total of fifty-three male subjects (72·2 (sd 4·68) years) with sarcopenia (class I or II) completed this randomised double-blind placebo-controlled study. All the participants underwent a 12-week guided resistance training programme (three sessions per week) and were supplemented with either collagen peptides (treatment group (TG)) (15 g/d) or silica as placebo (placebo group (PG)). Fat-free mass (FFM), fat mass (FM) and bone mass (BM) were measured before and after the intervention using dual-energy X-ray absorptiometry. Isokinetic quadriceps strength (IQS) of the right leg was determined and sensory motor control (SMC) was investigated by a standardised one-leg stabilisation test. Following the training programme, all the subjects showed significantly higher (P<0·01) levels for FFM, BM, IQS and SMC with significantly lower (P<0·01) levels for FM. The effect was significantly more pronounced in subjects receiving collagen peptides: FFM (TG +4·2 (sd 2·31) kg/PG +2·9 (sd 1·84) kg; P<0·05); IQS (TG +16·5 (sd 12·9) Nm/PG +7·3 (sd 13·2) Nm; P<0·05); and FM (TG -5·4 (sd 3·17) kg/PG -3·5 (sd 2·16) kg; P<0·05). Our data demonstrate that compared with placebo, collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM, muscle strength and the loss in FM.

Low-resolution structure determination of Na(+)-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae by ab initio phasing and electron microscopy.

A low-resolution structure of the Na(+)-translocating NADH:ubiquinone oxidoreductase from the human pathogen Vibrio cholerae was determined by ab initio phasing and independently confirmed by electron microscopy. This multi-subunit membrane-protein complex (molecular weight 210 kDa) generates an Na(+) gradient that is essential for substrate uptake, motility, pathogenicity and efflux of antibiotics. The obtained 16 Å resolution electron density-map revealed an asymmetric particle with a central region of low electron density and a putative detergent region, and allowed the identification of the transmembrane regions of the complex.

A soy-based supplement alters energy metabolism but not the exercise-induced stress response.

OBJECTIVE: To determine the changes in endurance capacity as well as in metabolic, hormonal and inflammatory markers induced by endurance training combined with a soy,protein based supplement. DESIGN: Randomized controlled study consisting of moderate endurance training without (GO) or with (G1) a soy protein based supplement. SUBJECTS: Two groups of 15 subjects (10 males and 5 females in each group): healthy sports students aged 23.6 +/- 1.9 years. MEASUREMENTS: Body composition (body mass (BM), body density (BD) by air displacement) and physical fitness (determined by treadmill ergometry) were measured at baseline and after 6 weeks of the intervention; changes in circulating metabolic and hormonal parameters (glucose, lactate, urea, uric acid, ammonia, cortisol, insulin, IGF-1), and exercise-induced stress and inflammatory markers (CK, LDH, myoglobin, hs-CRP, IL-6, IL-10, blood cell counts) were determined after the intervention period in afield test (11.5 km running on hilly ground). RESULTS: 30 participants completed the 6-week study; 28 students were able to perform the field test. No significant changes in BM and BD were noted after intervention with only slight increases in running performance and maximum aerobic capacity in the total group (2%, p=0.016). Subjects in the G1 group showed significant improvements in running velocity and lower lactate values following the intervention (-12%, p=0,003). In addition, the G1 group showed significantly lower differences in the exercise-induced increase of metabolic parameters (triglycerides, uric acid) and insulin in the post-exercise recovery period. CONCLUSIONS: Our data suggest that moderate endurance training in combination with a soy-based protein supplement improves aerobic energy supply and metabolic function in healthy sports students, even without changes in body composition and without changes in the exercise-induced stress and inflammatory reaction.

Do patients with low back pain remember physiotherapists' advice? A mixed-methods study on patient-therapist communication.

OBJECTIVES: The primary aim of this study was to determine if the advice physiotherapists think they provide to patients with low back pain (LBP) is what the patients remember and take away from the clinical encounter. The secondary aim was to determine which factors may influence the retention of this advice. METHODS: The first component of the study used questionnaires completed by patients and therapists after the initial visit. Related questionnaires of patients and therapists were screened for inconsistencies. The second component of the study involved semi-structured interviews. RESULTS: Ninety pairs of questionnaires were completed. Therapists provided patients with one (N = 90), two (N = 85) or three (N = 51) items of advice regarding the management of their LBP. All patients remembered the first item of advice, 92% remembered a second, and 67% remembered the third piece of advice. All items of advice were deemed either 'relevant' or 'very relevant' by 97% of the patients. After the analysis of 14 interviews, data saturation was reached. Four themes emerged from the data analysis of the interviews: (a) Evaluation type, (b) Exercise factors, (c) Patient concerns about their diagnosis, and (d) Patient expectations. DISCUSSION: In most cases, patients remembered what therapists told them and considered that the advice provided was relevant. Based on the qualitative data, patients were more likely to remember what therapists said when: (a) shared decision making was used during the initial encounter, (b) prescribed exercises were simple to perform and few in number, (c) patients' concerns about their diagnosis were addressed, and (d) patients' expectations were identified and addressed.

Mask-based approach to phasing of single-particle diffraction data. II. Likelihood-based selection criteria.

A new type of mask-selection criterion is suggested for mask-based phasing. In this phasing approach, a large number of connected molecular masks are randomly generated. Structure-factor phases corresponding to a trial mask are accepted as an admissible solution of the phase problem if the mask satisfies some specified selection rules that are key to success. The admissible phase sets are aligned and averaged to give a preliminary solution of the phase problem. The new selection rule is based on the likelihood of the generated mask. It is defined as the probability of reproducing the observed structure-factor magnitudes by placing atoms randomly into the mask. While the result of the direct comparison of mask structure-factor magnitudes with observed ones using a correlation coefficient is highly dominated by a few very strong low-resolution reflections, a new method gives higher weight to relatively weak high-resolution reflections that allows them to be phased accurately. This mask-based phasing procedure with likelihood-based selection has been applied to simulated single-particle diffraction data of the photosystem II monomer. The phase set obtained resulted in a 16 Šresolution Fourier synthesis (more than 4000 reflections) with 98% correlation with the exact phase set and 69% correlation for about 2000 reflections in the highest resolution shell (20-16 Å). This work also addresses another essential problem of phasing methods, namely adequate estimation of the resolution achieved. A model-trapping analysis of the phase sets obtained by the mask-based phasing procedure suggests that the widely used `50% shell correlation' criterion may be too optimistic in some cases.

Comprehensive lifestyle intervention vs soy protein-based meal regimen in non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become one of the leading causes of liver disease in the western world. In obese patients weight reduction is recommended. Up to now there are no specific guidelines for weight loss in order to reduce hepatic fat content. AIM: To investigate the effects of a 24-wk guided lifestyle intervention program compared to a meal replacement regimen based on soy protein. METHODS: Twenty-six subjects with NASH participated in a randomized single-center study. They were randomly assigned to either meal replacement group (MR-G) with soy-yogurt-honey preparation or to guided lifestyle change group (LC-G) with endurance activity and nutrition counselling. Serum alanine transaminase (ALT), aspartate transaminase (AST), lipid parameters, and adipokines were measured. Liver fat content and lipid composition were determined by magnetic resonance imaging and magnetic resonance spectroscopy. Body fat mass and lean body mass were assessed using Bod Pod® device. Pre- and post-intervention monitoring of parameters was performed. Statistical analyses were conducted with SPSS software, results were expressed as median (interquartile range). RESULTS: Twenty-two subjects (MR-G, n = 11 and LC-G, n = 11) completed the study (9 women, 13 men; age 52.1 (15.0) years, body mass index (BMI) 32.3 (3.3) kg/m²). In both groups a significant weight loss was achieved (MR-G: -6.4 (3.6) kg, P < 0.01; LC-G: -9.1 (10.4) kg, P < 0.01). BMI dropped in both groups (MR-G: -2.3 (1.5) kg/m2, P = 0.003; LC-G: -3.0 (3.4) kg/m2, P = 0.006). Internal fat and hepatic lipid content were markedly reduced in both groups in comparable amount. There was a strong correlation between reduction in liver fat and decrease in ALT. Likewise, both groups showed an improvement in glycemic control and lipid profile. Changes in adipokines, particularly in adiponectin and leptin were closely related to intrahepatic lipid changes. CONCLUSION: Comprehensive lifestyle intervention and meal replacement regimen have comparable effects on body and liver fat, as well as decrease in markers of hepatic inflammation among NASH patients.

Lipid profiles of persons with paraplegia and tetraplegia: sex differences.

BACKGROUND/OBJECTIVE: To examine the lipoprotein profiles of men and women with paraplegia and tetraplegia. Impairment of the sympathetic nervous system (dependent on the level of injury) and the extent of physical capacity and activity were correlated with the lipid profile in men with spinal cord injury (SCI). Sex-related differences of the lipoprotein profiles could be found in nondisabled and premenopausal women with SCI mainly because of the different effects of sexual hormones. METHODS: Lipoprotein profiles of 112 participants with SCI (32 premenopausal women, 80 men) were analyzed and correlated to sex, lesion level, and physical performance capacity. RESULTS: Women with tetraplegia or paraplegia showed significantly higher levels of high-density lipoprotein and lower ratios of total cholesterol to high-density lipoprotein-cholesterol compared with men with corresponding lesion levels, without a difference in peak oxygen consumption. Concentrations of very-low-density lipoproteins were lower in women with paraplegia than in men with paraplegia; no differences were found in total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Sex-independent elevations in total cholesterol and low-density lipoprotein-cholesterol were associated with paraplegia, and sex-independent elevations in triglyceride levels were associated with tetraplegia. CONCLUSIONS: Persons with SCI showed sex-related differences in their lipoprotein profiles. Independent of physical fitness, the lipoprotein profile of premenopausal women with SCI did not exhibit the adverse lipoprotein characteristics observed in men with SCI, probably because of the influence of sexual hormones independent of lesion level.

Frequency of secondary dyslipidemia in obese children.

OBJECTIVE: This paper reports the frequency, type, and degree of dyslipidemia in obese children before therapeutic intervention. The relationships between lipid values and weight status, as well as lipid values and physical fitness, of these children were also investigated. DESIGN AND METHODS: The initial examination of the Freiburg Intervention Trial for Obese Children (FITOC) measured the values of triglycerides (TG), total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in 546 obese children aged 7-12 (body mass index [BMI] > 97th percentile), and compared these values with those of the age- and sex-specific reference group in the Lipid Research Clinics Population Studies Data Book (LRC). Four groups were selected according to the following scheme: A, Normolipidemia; B, Hyper-LDL-cholesterolemia alone; C, Hypo-HDL-C + hypertriglyceridemia; D, Combined hyperlipidemia = Hyper-LDL-C + hypertriglyceridemia. Body mass index, BMI-SDS (corrected BMI), and physical performance in watt/kg body weight were measured. RESULTS: A total of 45.8% of the overweight children showed an abnormal lipid profile. Ten percent of the children had high LDL-C levels (group B), while 15% had increased LDL-C and increased TG (group D) (higher prevalence in boys). In 18.9% we found increased TG, combined with decreased HDL-C values (group C). CONCLUSION: Obese children are at risk of dyslipoproteinemia and related diseases. Children with the highest BMI-SDS and lowest physical fitness have the lowest HDL-C values and increased TG, indicating a higher risk for the metabolic syndrome.

Applying the Optimized CO Rebreathing Method for Measuring Blood Volumes and Hemoglobin Mass in Heart Failure Patients.

Introduction: Determination of blood volume, red cell volume, and plasma volume contributes to the understanding of the pathophysiology in heart failure, especially concerning anemia and volume load. The optimized carbon monoxide (CO)-rebreathing method (oCORM) is used to determine these parameters and hemoglobin mass (Hbmass) in exercise physiology. The applicability of oCORM to determine the intravascular volumes and Hbmass in heart failure patients is currently undetermined because assumptions concerning CO kinetics with oCORM rely on healthy subjects with a normal ejection fraction. Therefore, the aim of the present study is to determine the applicability and the systematic error of oCORM arising from a reduced EF when oCORM is used for measurement of intravascular volumes and Hbmass in heart failure patients. Methods: oCORM was performed in 21 patients with heart failure and a reduced ejection fraction (EF) of < 30% (EFsev) and 25 controls (CONT). CO kinetics in capillary blood was studied 3-15 min after commencement of CO rebreathing. Differences in CO kinetics between the groups were assessed using a generalized linear model. The systematic error for determination of Hbmass with oCORM arising from differences in CO kinetics was assessed using the Monte Carlo method. Results: The CO kinetics was significantly different between EFsev and CONT. In both groups, exposure to CO led to a COHb increase to 6.0 ± 1.0% 3 min after CO rebreathing. There were no CO related side effects or any clinical symptoms. Monte Carlo simulation quantifies the systematic error for determination of Hbmass arising from an impaired ejection fraction to be -0.88%. Conclusion: Our results indicate an impaired vascular mixing of CO when EF is severely reduced. When Hbmass is determined using the original oCORM protocol in heart failure patients with a reduced EF, the systematic underestimation of about 1% should be considered. However, the error arising from this impaired vascular mixing appears small and clinically negligible. Furthermore, application of oCORM was safe and not related to any side effects resulting from CO exposure. In conclusion, oCORM can be used for assessing intravascular volumes and Hbmass in patients with a reduced EF.

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension.

AIM: To investigate the potential effect of inhibitors of phosphodiesterase-5 (PDE-5) for therapy of portal hypertension in liver cirrhosis. METHODS: In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase (eNOS), inducible NO synthase (iNOS), soluble guanylate cyclase subunits α1 and ß1 (sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil (0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers. RESULTS: Hepatic gene expression of eNOS (2.2-fold; P = 0.003), sGCa1 (1.7-fold; P = 0.003), sGCb1 (3.0-fold; P = 0.003), and PDE-5 (11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5 (7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats (P = 0.024), + 85% in cirrhotic rats (P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION: Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.

Signaling ammonium across membranes through an ammonium sensor histidine kinase.

Sensing and uptake of external ammonium is essential for anaerobic ammonium-oxidizing (anammox) bacteria, and is typically the domain of the ubiquitous Amt/Rh ammonium transporters. Here, we report on the structure and function of an ammonium sensor/transducer from the anammox bacterium "Candidatus Kuenenia stuttgartiensis" that combines a membrane-integral ammonium transporter domain with a fused histidine kinase. It contains a high-affinity ammonium binding site not present in assimilatory Amt proteins. The levels of phosphorylated histidine in the kinase are coupled to the presence of ammonium, as conformational changes during signal recognition by the Amt module are transduced internally to modulate the kinase activity. The structural analysis of this ammonium sensor by X-ray crystallography and small-angle X-ray-scattering reveals a flexible, bipartite system that recruits a large uptake transporter as a sensory module and modulates its functionality to achieve a mechanistic coupling to a kinase domain in order to trigger downstream signaling events.

Mask-based approach to phasing of single-particle diffraction data.

A Monte Carlo-type approach for low- and medium-resolution phasing of single-particle diffraction data is suggested. Firstly, the single-particle phase problem is substituted with the phase problem for an imaginary crystal. A unit cell of this crystal contains a single isolated particle surrounded by a large volume of bulk solvent. The developed phasing procedure then generates a large number of connected and finite molecular masks, calculates their Fourier coefficients, selects the sets with magnitudes that are highly correlated with the experimental values and finally aligns the selected phase sets and calculates the averaged phase values. A test with the known structure of monomeric photosystem II resulted in phases that have 97% correlation with the exact phases in the full 25 Å resolution shell (1054 structure factors) and correlations of 99, 94, 81 and 79% for the resolution shells ∞-60, 60-40, 40-30 and 30-25 Å, respectively. The same procedure may be used for crystallographic ab initio phasing.

Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study.

OBJECTIVE: The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS: We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment. RESULTS: At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS: The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.

Effect of fluvastatin slow-release on low density lipoprotein (LDL) subfractions in patients with type 2 diabetes mellitus: baseline LDL profile determines specific mode of action.

The objective of this study was to determine the effect of slow-release (XL) fluvastatin on low density lipoprotein (LDL) subfractions in type 2 diabetes. A multicenter, double-blind, randomized, parallel-group comparison of fluvastatin XL 80 mg (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with type 2 diabetes (HbA1c: 7.2 +/- 1.0%, LDL cholesterol (LDL-C): 3.4 +/- 0.7 mmol/liter, high density lipoprotein cholesterol: 1.1 +/- 0.3 mmol/liter, and triglycerides (TG): 2.4 +/- 1.4 mmol/liter). At baseline and on treatment, plasma lipoproteins were isolated and quantified. Eight weeks of fluvastatin treatment decreased total cholesterol (-23.0%, P < 0.001), LDL-C (-29%, P < 0.001) and TG (-18%, P < 0.001), compared with placebo. At baseline, there was a preponderance of dense LDL (dLDL) (apolipoprotein B in LDL-5 plus LDL-6 > 25 mg/dl) in 79% of patients, among whom fluvastatin decreased all LDL subfractions, reductions in dLDL being greatest (-28%, P = 0.001; cholesterol in dLDL -29%). In patients with low baseline dLDL (apolipoprotein B in LDL-5 plus LDL-6

Triglyceride-rich lipoproteins are associated with hypertension in preeclampsia.

Disorders of the lipoprotein metabolism are a major cause of endothelial dysfunction that may result in hypertension and proteinuria, clinical hallmarks of preeclampsia (PE). Lipoproteins and low-density lipoprotein (LDL) subfractions were investigated in 15 women with severe PE and compared with 23 women with a normal course of pregnancy. Compared with normal pregnancy, in PE apolipoprotein (apo)B in very low-density lipoprotein was increased by 76% (P = 0.008), and the triglyceride content of intermediate dense lipoproteins (IDL) was increased by 51% (P < 0.001); cholesterol and apoB in LDL were decreased by 26% (P = 0.005) and 23% (P = 0.016), respectively. Although not significant, the LDL profile was dominated by the most buoyant LDL-1. ApoB in the most dense LDL (dLDL), namely LDL-5 and LDL-6, was significantly decreased by 49% (P < 0.001) and 55% (P < 0.001), respectively. Diastolic blood pressure was positively correlated with the triglyceride content of IDL (r = 6.31; P < 0.001 and r = 0.352; P = 0.033 by partial correlation controlling for the presence or absence of PE) and negatively correlated with the concentration of apoB in dLDL (r = -0.500; P = 0.002). In addition, IDL triglycerides correlated negatively with infant birth weight percentile (r = -0.373; P = 0.027) and positively with proteinuria (r = 0.430; P = 0.014). Low birth weight was associated with high IDL triglycerides and low rather than high concentrations of dLDL. Triglyceride-rich remnants are known to cause endothelial dysfunction. Because the triglyceride content of IDL was positively correlated with elevated blood pressure and proteinuria, triglyceride-rich remnant lipoproteins might contribute to the pathophysiology of PE.

Quantitative measurement of carotid intima-media roughness--effect of age and manifest coronary artery disease.

UNLABELLED: Atherosclerotic changes of the common carotid artery (CCA) may appear like irregularities of the intima-media thickness (abbreviated as IM roughness) in B-mode ultrasound. The purposes of the present study were to investigate whether the CCA IM roughness changes with age and differs between individuals presumed to be healthy and patients with coronary artery disease (CAD). METHODS AND RESULTS: Based on a new automatic identification (AI) program, the segmental intima-media thickness (IMT) and IM roughness of the CCA far wall were measured in B-mode images of 15 younger and 22 older volunteers presumed to be healthy, and 46 patients with known CAD. The mean and maximum CCA IMT were lowest in the young group (0.55+/-0.05; 0.65+/-0.06 mm), higher in the older group (0.77+/-0.16; 0.87+/-0.18 mm) and highest in CAD patients (0.88+/-0.18; 1.01+/-0.27 mm) (P<0.01 among all groups). The CCA IM roughness was greatest by far in the CAD patients (0.075+/-0.02 mm; P<0.01 vs. both groups) and increased only slightly with age (younger: 0.035+/-0.008 mm; older: 0.040+/-0.014 mm; P<0.05). Areas under the curve (AUC) of receiver-operating characteristic curves (ROC) predicting patients with CAD were higher for the CCA IM roughness (0.80) than for the mean (0.66) and maximum IMT (0.71). CONCLUSIONS: It is suggested that the CCA IM roughness increases with age, and helps to discriminate between individuals presumed to be healthy and patients with manifest CAD better than the CCA mean and maximum IMT.