Reference values of spirometry for Finnish adults.

BACKGROUND: Diagnostic assessment of lung function necessitates up-to-date reference values. The aim of this study was to estimate reference values for spirometry for the Finnish population between 18 and 80 years and to compare them with the existing Finnish, European and the recently published global GLI2012 reference values. METHODS: Spirometry was performed for 1380 adults in the population-based FinEsS studies and for 662 healthy non-smoking volunteer adults. Detailed predefined questionnaire screening of diseases and symptoms, and quality control of spirometry yielded a sample of 1000 native Finns (387 men) healthy non-smokers aged 18-83 years. Sex-specific reference values, which are estimated using the GAMLSS method and adjusted for age and height, are provided. RESULTS: The predicted values for lung volumes are larger than those obtained by GLI2012 prediction for the Caucasian subgroup for forced vital capacity (FVC) by an average 6·2% and 5·1% and forced expiratory volume in 1 s (FEV1) by an average 4·2% and 3·0% in men and women, respectively. GLI2012 slightly overestimated the ratio FEV1/FVC with an age-dependent trend. Most reference equations from other European countries, with the exception of the Swiss SAPALDIA study, showed an underestimation of FVC and FEV1 to varying degrees, and a slight overestimation of FEV1/FVC. CONCLUSION: This study offers up-to-date reference values of spirometry for native Finns with a wide age range. The GLI2012 predictions seem not to be suitable for clinical use for native Finns due to underestimation of lung volumes.

Myocardial and peripheral vascular functional adaptation to exercise training.

Exercise training seems to restore impaired vascular function in both peripheral and myocardial vessels in patients with coronary artery and peripheral vascular disease or in patients with risk factors for these diseases. However, the results on the effects of exercise training on vascular function in apparently healthy subjects are controversial. We studied the effects of long-term volitionally increased physical activity on peripheral and myocardial vascular function in nine young healthy male monozygotic twin pairs discordant for physical activity and fitness. The brothers were divided into more (MAG) and less active groups according to physical activity and fitness. The difference between groups in VO(2max) was 18+/-10% (P<0.001). Myocardial perfusion at rest, during adenosine-induced vasodilatation and during cold-pressor test and myocardial oxygen consumption were measured with positron emission tomography. In addition, endothelial function was measured using ultrasound in brachial and left anterior descending coronary arteries, and standard echocardiographic measures were taken. No differences were observed in myocardial perfusion measurements between groups. MAG tended to have a lower oxygen extraction fraction (P=0.06), but oxygen consumption was similar between the groups. No differences were found in coronary artery, myocardial resistance vessel or peripheral endothelial function between groups. These results suggest that when the effects of heredity are controlled, myocardial perfusion reserve and endothelial function, both in peripheral arteries and myocardial vessels, are not enhanced by increased physical activity and fitness in young healthy adult men.

Diabetic background retinopathy is associated with impaired coronary vasoreactivity in people with Type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether diabetic background retinopathy is associated with reduced coronary vasoreactivity in people with Type 1 diabetes. METHODS: A total of 21 men with Type 1 diabetes were investigated, including 9 men with background retinopathy and 12 men without retinopathy. In addition, 12 non-diabetic, age-matched subjects were studied. All subjects were non-smokers, otherwise healthy and had no other diabetic complications. Resting myocardial blood flow and hyperaemic dipyridamole-stimulated flow (dipyridamole, 0.56 mg/kg during a 4-min period), a measure of coronary vasoreactivity, were measured during euglycaemic hyperinsulinaemic clamp (1 mU x kg(-1) x min(-1)) using positron emission tomography and oxygen-15-labelled water. RESULTS: Resting myocardial blood flow (0.82 +/- 0.13 vs 0.96 +/- 0.23 vs 0.88 +/- 0.25 ml x g(-1) x min(-1), with vs without retinopathy vs non-diabetic subjects) and coronary vascular resistance (111.2 +/- 23.4 vs 95.5 +/- 15.8 vs 101.9 +/- 31.5 mmHg x min x g x ml(-1) respectively) were not significantly different between the groups. Dipyridamole infusion induced an increase in blood flow and a decrease in coronary vascular resistance in all study subjects (p<0.001). However, dipyridamole-stimulated flow and coronary vascular resistance were blunted in diabetic patients with retinopathy (2.9 +/- 0.9 ml x g(-1) x min(-1) and 34.1 +/- 11.3 mmHg x min x g x ml(-1)) when compared to diabetic patients without retinopathy (4.0 +/- 1.3 ml x g(-1) x min(-1), p=0.04 and 24.6 +/- 7.5 mmHg x min x g x ml(-1), p=0.03) or non-diabetic subjects (4.5 +/- 1.4 ml x g(-1) x min(-1) p=0.008 and 22.2 +/- 8.7 mmHg x min x g x ml(-1), p=0.01). Myocardial flow reserve was impaired in diabetic patients with retinopathy (3.6 +/- 1.0) when compared to non-diabetic subjects (5.3 +/- 1.9, p=0.02) but not significantly reduced when compared to diabetic patients without retinopathy (4.2 +/- 1.4, p=0.2). CONCLUSIONS/INTERPRETATION: Diabetic background retinopathy appears to be associated with impaired coronary vasoreactivity in young people with Type 1 diabetes.

Correlation of transthoracic Doppler echocardiography and magnetic resonance imaging in measuring left anterior descending artery flow velocity and time-course of dipyridamole-induced coronary flow increase.

There is an increasing need for new, functional and more quantitative parameters to assess coronary arterial function, for the purposes of evidence-based medicine. Coronary arterial function has been widely studied using pharmacological stimulation induced by dipyridamole or adenosine. Coronary flow reserve (CFR), defined as the ratio of pharmacologically induced hyperemic flow divided by basal flow, has been found to be an important functional index in both the clinical and subclinical stages of cardiovascular diseases. Ten healthy male volunteers were studied to compare transthoracic Doppler echocardiography (TTE) and MRI for measuring left anterior descending coronary artery (LAD) flow velocity and CFR. Additionally, the time-response curve of dipyridamole infusion was studied in five healthy males using TTE. Assessment of blood flow velocity, measured as MDV, PDV and VTI indicated Pearson's correlation coefficients of 0.88, 0.85 and 0.70, respectively, between flow velocity measurements performed using TTE and MRI. The results indicate that, despite minor differences in LAD diastolic velocities measured by TTE and MRI, the correlation of the LAD diastolic velocities measured using both methods are good and both methods are feasible for measuring CFR. Moreover, TTE has the unique capability of continuous measurement of LAD flow velocity, which allowed assessment of the time-response curve for dipyridamole-induced increase in LAD flow velocity in this study. This study indicates that the TTE method may be used in sequential or on-line monitoring of LAD blood flow velocity and therefore can be applied to evaluate the time- or dose-response effects of infused drugs in the coronary circulation of humans.

Decreased large artery distensibility in borderline hypertension is related to increased in vivo low-density lipoprotein oxidation.

The present study tested the hypothesis that reduced arterial elasticity seen in hypertension is related to increased oxidation of LDL. Fifteen men with borderline hypertension (BHT), with blood pressure values classified as high normal (systolic blood pressure 130-140 mmHg or diastolic blood pressure 85-89 mmHg) were included. The control group comprised 22 men with normal blood pressure values (<135/80 mmHg) matched for age, body size and LDL-cholesterol level. Distensibility of aorta was measured using magnetic resonance imaging, and distensibility of the common carotid artery using ultrasound. Baseline LDL diene conjugation was used as a marker for ox-LDL. Aortic and carotid distensibilities were lower in the BHT men than in controls (1.4 +/- 0.6 vs. 1.9 +/- 0.6%/10 mmHg, p<0.05 for aortic distensibility; 2.9 +/- 0.9 vs. 3.6 +/- 0.6%/10 mmHg, p<0.05 for carotid distensibility). Ox-LDL was significantly higher in the BHT men than in controls (44 +/-15 vs. 28 +/- 8 micromol/L, p<0.01). In univariate analysis, ox-LDL associated with aortic distensibility (r=-0.43, p<0.05). In multivariate analysis, the differences in distensibilities between the groups disappeared when the values were adjusted for ox-LDL. These data show decreased arterial elasticity and increased LDL oxidation in young men with borderline hypertension, and suggest that oxidative modification of LDL particles may play a pathophysiological role in the development of reduced arterial distensibility in hypertension.

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness.

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.

Assessing coronary sinus blood flow in patients with coronary artery disease: a comparison of phase-contrast MR imaging with positron emission tomography.

OBJECTIVE: This study was performed to determine whether MR imaging can be used to reliably measure global myocardial blood flow and coronary flow reserve in patients with coronary artery disease as compared with such measurements obtained by positron emission tomography (PET). SUBJECTS AND METHODS: We measured myocardial blood flow first at baseline and then after dipyridamole-induced hyperemia in 20 patients with coronary artery disease. Myocardial blood flow as revealed by MR imaging was calculated by dividing coronary sinus flow by the left ventricular mass. Coronary flow reserve was calculated by dividing the rate of hyperemic flow by the rate of baseline flow. RESULTS: Using MR imaging, myocardial blood flow at baseline was 0.73 +/- 0.23 mL x min(-1) x g(-1), and at hyperemia the blood flow was 1.43 +/- 0.37 mL x min(-1) x g(-1), yielding an average coronary flow reserve of 1.99 +/- 0.47. Using PET, myocardial blood flow was 0.89 +/- 0.21 mL x min(-1) x g(-1) at baseline and 1.56 +/- 0.42 mL x min(-1) x g(-1) at hyperemia, yielding an average coronary flow reserve of 1.77 +/- 0.36. The correlation of myocardial blood flow and coronary flow reserve measurements for these two methods was an r of 0.80 (p < 0.01) and an r of 0.50 (p < 0.05), respectively. CONCLUSION: This study shows that myocardial blood flow measurements obtained using MR imaging have a good correlation with corresponding PET measurements. Coronary flow reserve measurements obtained using MR imaging had only moderate correlation with PET-obtained measurements. Our results suggest that MR imaging flow quantification could potentially be used for measuring global myocardial blood flow in patients in whom interventional treatment for coronary artery disease is being evaluated.

Reduced myocardial flow reserve relates to increased carotid intima-media thickness in healthy young men.

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36+/-4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT (P=0.006), and was 5.2+/-1.9 in the lowest quartile for IMT and 3.7+/-1.2 in the highest (P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve (r=-0.35, P=0.01) and directly with IMT (r=0.51, P<0.001). The association between flow reserve and IMT remained significant (P< or =0.01) in multivariate regression model including age, blood pressure, left ventricular mass, ox-LDL, total cholesterol, HDL-cholesterol and triglycerides as covariates. These data support the concept that reduced myocardial flow reserve reflects subclinical atherosclerosis in asymptomatic subjects, and suggest that increased lipoprotein oxidation is directly related to early structural and functional atherosclerotic vascular changes.

Global myocardial blood flow and global flow reserve measurements by MRI and PET are comparable.

Coronary flow reserve (CFR) measurements have been widely used in assessing the functional significance of coronary artery stenosis because they are more sensitive in predicting major cardiac events than angiographically detected reductions of coronary arteries. Myocardial blood flow can be determined by measuring coronary sinus (CS) flow with velocity-encoded cine magnetic resonance imaging (VEC-MRI). The purpose of this study was to compare global myocardial blood flow (MBF) and CFR measured using VEC-MRI with MBF and CFR measured using positron emission tomography (PET). We measured MBF at baseline and after dipyridamole-induced hyperemia in 12 male volunteers with VEC-MRI and PET. With VEC-MRI, MBF was 0.64 +/- 0.09 (ml/min/g) at baseline and 1.59 +/- 0.79 (ml/min/g) at hyperemia, which yielded an average CFR of 2.51 +/- 1.29. With PET, MBF was 0.65 +/- 0.20 (ml/min/g) at baseline and 1.78 +/- 0.72 (ml/min/g) at hyperemia, which yielded an average CFR of 2.79 +/- 0.97. The correlation of MBFs between these two methods was good (r = 0.82, P < 0.001). The CFRs measured by MRI correlated well with those measured using PET (r = 0.76, P < 0.004). These results suggest that MRI is a useful and accurate method to measure global MBF and CFR. Therefore, it would be suitable for studying risk factor modifications of vascular function at an early stage in healthy volunteers.

Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy.

We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33-66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness. LDL oxidation was found in chemical analyses to be due to conjugated fatty acids in cholesteryl esters and triglycerides. Regression analysis indicated that the carotid intima-media thickness and the ratio of LDL diene conjugation to LDL cholesterol (the ox-LDL:LDL ratio) were the only factors associated independently with the severity of coronary atherosclerosis. The patients with multi-vessel disease who did not use lipid lowering therapy had a 50% thicker carotid intima media (P = 0.030) and a 41% higher ox-LDL:LDL ratio (P = 0.020) than patients with normal vessels. Further, patients with multi-vessel disease on statin therapy had a 24% lower ox-LDL:LDL ratio than the subjects with multi-vessel disease who did not use lipid lowering drugs (P = 0.027), although the concentration of LDL cholesterol did not differ between the groups. This study supports the hypothesis that lipid oxidation plays a role in the development of atherosclerosis.

Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography.

Detection of early vascular changes indicated by lowered coronary flow reserve (CFR) would allow early treatment and prevention of atherosclerosis. The purpose of this study was to test whether it is possible to reproducibly measure CFR with transthoracic Doppler echocardiography (TTE) in healthy volunteers. We measured CFR using dipyridamole infusion in ten healthy male volunteers with two methods: TTE and positron emission tomography (PET) with oxygen-15-labelled water (group A). However, CFR was assessed twice with TTE in eight healthy male volunteers (group B) to study the reproducibility of this method. We compared CFRs obtained using TTE flow measurements in the left anterior descending coronary artery (LAD) and PET flow measurements in the corresponding myocardial area. Coronary flow in LAD could be measured in all subjects using TTE. By TTE, an average CFR based on peak diastolic flow velocity (PDV) was 2.72 +/- 1.16, mean diastolic flow velocity (MDV) 2.56 +/- 1.06 and velocity time integral (VTI) 1.87 +/- 0.49. The results were reproducible in two repeated TTE studies (coefficient of variation in MDV 6.1 +/- 4.3%, n=8). By PET, CFR was 2.52 +/- 0.84. CFR assessed by TTE correlated closely with that measured by PET (MDV r=0.942, P<0.001; PDV r=0.912, P<0.002 and VTI r=0.888, P<0.006) and intraclass correlation was 0.929 (MDV) and tolerance limits for differences of CFRs was -0.78 to 0.72. We show that CFR measured by TTE has an excellent correlation with CFR measured by PET. We also found that TTE measurements of CFR were highly reproducible.

Technical achievement: transthoracic Doppler echocardiography can be used to detect LAD restenosis after coronary angioplasty.

We investigated the capability of transthoracic Doppler echocardiography (TTE) to detect and quantify the severity of restenosis in the left anterior descending coronary artery (LAD) after percutaneous transluminal coronary angioplasty (PTCA). We studied 10 consecutive patients assigned for quantitative coronary angiography (qCA) due to a recurrent angina pectoris after PTCA of the LAD. The LAD was visualized by TTE, and the presence of local turbulence and an increase in the blood flow velocity was regarded to indicate coronary stenosis. To assess the severity of the stenosis, the increase of blood flow velocity was measured. Angiography showed stenoses of various degrees (27-100%) in all patients. All stenoses were detectable using TTE. Moreover, the ratio of maximal blood flow velocity at the site of stenosis to the pre-stenotic blood flow velocity (M/P-ratio) correlated significantly with the reduction of the luminal diameter of LAD (r = 0.85, P < 0.003). A M/P-ratio higher than 3.0 predicted a diameter reduction of 50% or higher with sensitivity and specificity of 100% in patients with a subtotal stenosis (n = 9). Our results indicate that stenoses in the LAD could be found and the severity of the stenoses could be quantified reliably with TTE. This approach is totally non-invasive and less expensive than coronary angiography and can be used clinically in clarifying restenosis after coronary angioplasty.

Noninvasive assessment of brachial artery endothelial function with digital ultrasound and 13-MHz scanning frequency: feasibility of measuring the true inner luminal diameter using the intima-lumen interface.

Previous studies assessing endothelial function as flow-mediated changes in the brachial artery diameter have not been able to measure the true inner luminal diameter. This is due to the lack of image quality, which has hampered the visualisation of the lumen-intimal interface. Because increases in resolution and scanning frequency have recently led to improved ultrasound (US) image quality, we assessed the feasibility of measuring the true brachial artery diameter using digital US and 13-MHz scanning frequency. Satisfactory true inner diameter measurements were obtained in all subjects (n = 148, middle-aged men, mean age 54 +/- 7 y) participating in a risk factor study. At baseline flow, the intima to intima diameter was 4.03 +/- 0.49 and 4.67 +/- 0.52 mm measured conventionally from the anterior to the posterior media-adventitia interface (difference 0.64 +/- 0.10 mm). After hyperaemia, the intima to intima diameter was 4.23 +/- 0.46 mm and the adventitia to adventitia diameter 4.86 +/- 0.50 mm. Flow-mediated dilation (FMD) expressed as the percentage change from the baseline diameter measured 5.3 +/- 4.3% using the true inner diameters and 4.3 +/- 3.7% using the conventional outer diameters. The difference in FMD values was systematic, and there was a good linear correlation between them (r = 0.93, p < 0.0001). If FMD is presented as the percentage change from baseline to hyperaemia, this new method gives values that are approximately 1% unit higher, compared with values when brachial luminal diameter is measured in the conventional way between the adventitia-media interfaces.

Assessment of coronary flow reserve using fast velocity-encoded cine MR imaging: validation study using positron emission tomography.

OBJECTIVE: Previous studies using intravascular Doppler sonography and positron emission tomography (PET) have shown that the hemodynamic significance of coronary artery stenosis can be evaluated by measuring coronary flow reserve. The purpose of this study was to assess whether MR imaging measurements of coronary flow reserve in the left anterior descending artery are comparable with those obtained with PET in the corresponding territory. SUBJECTS AND METHODS: MR imaging and PET flow measurements were obtained in 10 healthy volunteers. Blood flow velocity in the left anterior descending artery was measured with breath-hold velocity-encoded cine MR imaging before and after IV administration of dipyridamole. The coronary flow velocity reserve measured by MR imaging was compared with the myocardial perfusion reserve in the anterior myocardium quantified on using PET and (15)O-labeled water. RESULTS: The average flow velocity reserve in the left anterior descending artery measured on MR imaging was 2.44+/-1.14 in healthy volunteers, which was comparable with the myocardial perfusion reserve measured by PET (2.52+/-0.84). MR imaging and PET measurements of the coronary flow reserve showed a significant correlation (r = 0.79, p<0.01). CONCLUSION: MR imaging measurement of the flow velocity reserve in the proximal left anterior descending artery correlates well with the myocardial perfusion reserve obtained with PET and (15)O-labeled water.

Increased arterial intima-media thickness and in vivo LDL oxidation in young men with borderline hypertension.

We used borderline hypertension as a model for prehypertension to examine the early influences of elevated blood pressure on subclinical atherosclerosis, lipoprotein oxidation, and cardiac adaptation. Healthy men (age 37+/-4 years) were classified prospectively into 2 groups on the basis of having either borderline hypertension (systolic 130 to 140 mm Hg or diastolic 85 to 89 mm Hg, n=16) or normal (<130/85 mm Hg, n=22) blood pressure values during the previous 2 years. The groups were matched for age, body size, and serum cholesterol levels. High-resolution ultrasound was used to measure intima-media thickness (IMT) of the carotid and brachial arteries, cardiac dimensions, and brachial artery endothelial function. Baseline low-density lipoprotein (LDL)-diene conjugation was measured as an estimate of in vivo LDL oxidation (ox-LDL). Compared with normotensive controls, men with borderline hypertension had higher IMT of the carotid artery (0.58+/-0.06 versus 0.75+/-0.07 mm, P<0.001) and IMT of the brachial artery (0.45+/-0.05 versus 0.57+/-0.07 mm, P<0.001), and increased levels of ox-LDL (29+/-9 versus 47+/-17 mol/L, P<0.001), but similar endothelial function. Left ventricular mass was similar in both groups, but there were significant differences in left ventricular geometry. In multivariate analyses, the predictors of carotid IMT were 24-hour systolic blood pressure (P<0.001) and ox-LDL (P=0.10). The current study demonstrates evidence of increased subclinical atherosclerosis and ox-LDL in borderline hypertension. These results are consistent with the idea that enhanced ox-LDL may be one of the pathophysiological events related to development of atherosclerosis in men with borderline elevated blood pressure.

Reduced myocardial flow reserve does not impair exercise capacity in asymptomatic men.

We examined whether impaired coronary flow reserve in healthy men is associated with changes in cardiac performance and exercise-induced ischemia. A comparison between 7 asymptomatic men with low flow reserve (<3.5) and 8 men with normal flow reserve (>3.5) showed no differences in these parameters, suggesting that the mechanisms that control myocardial blood flow during exercise remain normal despite the alterations in the mechanisms that control the vasodilatory reaction to dipyridamole.

HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (statins) may enhance vascular endothelial function independent of their cholesterol lowering effect. To test this hypothesis, we surveyed two groups of patients (age 55+/-7, mean+/-SD) with coronary artery disease that were matched for age, blood pressure and serum lipid levels. Group 1 comprised 23 men without lipid-lowering medication and Group 2 included 22 patients with ongoing HMG CoA reductase inhibitor medication. Flow-mediated (endothelium-dependent) arterial dilatation (FMD) and nitrate-mediated (smooth muscle dependent) dilatation (NMD) were measured in the brachial artery using high resolution ultrasound. FMD was considerably higher in group 2 (4.3+/-2.6 vs. 2.6+/-2.8%; P<0.05). In multivariate regression model, statin use was the only significant (P<0.05) predictor of FMD. In all subjects, FMD correlated with statin dose (P<0.05 for trend). NMD was non-significantly higher in group 2 (11.4+/-5.0 vs. 9.0+/-4.2%, P=0. 08). We conclude that patients with established coronary artery disease on HMG CoA reductase inhibitor therapy have better vascular endothelial function than similar patients without the medication. These data provide further support for the idea that HMG CoA reductase inhibitors enhance endothelial function independent of their lipid-lowering effects. This may suggest that these drugs could be beneficial in secondary prevention of coronary artery disease regardless of the serum cholesterol concentration.

Constantly low HDL-cholesterol concentration relates to endothelial dysfunction and increased in vivo LDL-oxidation in healthy young men.

To test the hypothesis that low HDL-C concentration interferes with vascular endothelial function and lipoprotein oxidation, we measured endothelium-dependent flow mediated dilatation (FMD, %) of the brachial artery in young men (n=20) classified prospectively into two groups on basis of having either low or high HDL-C concentration over the past 2 years. As an estimate of in vivo low-density lipoprotein oxidation (ox-LDL), we measured LDL diene conjugation. FMD was present in the group with high HDL-C concentration, but impaired in the group with low HDL-C (5.5+/-3.2 vs 0.2+/-1.2%, P<0. 001). The group with high HDL-C level had significantly lower levels of ox-LDL compared to low HDL-C group (18.0+/-1.8 vs 22.9+/-4.4, P

Large-artery elastic properties in young men : relationships to serum lipoproteins and oxidized low-density lipoproteins.

Measures of arterial elasticity have been proposed as surrogate markers for asymptomatic atherosclerosis. We investigated the relations of serum lipoproteins, oxidized low-density lipoprotein (ox-LDL), and familial hypercholesterolemia (FH) to arterial elasticity among young men. As a marker of arterial elasticity we measured compliance in the thoracic aorta by using magnetic resonance imaging and in the common carotid artery by using ultrasound. LDL diene conjugation was used as a marker of ox-LDL. In study I, 25 healthy men (aged 29 to 39) were classified into 2 extreme groups according to previously measured high-density lipoprotein cholesterol to total cholesterol ratio (HDL-C/TC ratio). In study II, the healthy men were used as controls for 10 age matched asymptomatic patients with FH. In healthy men, the group with low HDL-C/TC ratio had decreased carotid artery compliance (2. 3+/-0.4% versus 1.9+/-0.5%/10 mm Hg, P=0.034). In univariate analysis, the compliance of the carotid artery associated with ox-LDL (r =-0.49, P=0.016) and HDL-C/TC ratio (r=0.41, P=0.040). In multivariate regression analyses, ox-LDL was the only independent determinant for compliance of the carotid artery (P=0.016). Aortic elasticity was not related to standard lipid variables, but the compliance of the ascending aorta associated with ox-LDL (r=-0.44, P=0.030). In FH patients, arterial elasticity was similar to that in controls. We conclude that elasticity of the common carotid artery is affected by serum lipid profile in young men. The current study demonstrates for the first time an in vivo association between ox-LDL and arterial elasticity suggesting that oxidative modification of LDL may play a role in the alteration of arterial wall elastic properties.

The polysialic acid units of the neural cell adhesion molecule N-CAM form filament bundle networks.

Polysialic acid is a developmentally regulated component in the neural cell adhesion molecule N-CAM which also occurs as the capsular polysaccharide of bacteria causing meningitis. Polysialic acid has been considered as a repulsive element that regulates intermolecular and intercellular adhesion. Using atomic force microscopy we unexpectedly find that oligomers of polysialic acid assemble with each other into filament bundle networks. Filaments were formed from oligomers containing 12 or more N-acetylneuraminic acid residues, and they were sensitive to sialidase digestion. The networks were also formed by the polysialic acid-containing carbohydrate units of N-CAM. The formation of filament bundles is a novel and unexpected property of polysialic acid and of short carbohydrate oligomers in general and represents a previously unrecognized molecular interaction mechanism which impacts both eukaryotic and prokaryotic cell-cell adhesions.