Rein Teesalu

High-sensitivity C-reactive protein affects central haemodynamics and augmentation index in apparently healthy persons.

Objective Among apparently healthy women and men, elevated levels of high-sensitivity C-reactive protein (hsCRP) predict the risk of cardiovascular events and may be useful for detecting subclinical atherosclerosis. The aim of this study was to investigate the associations between inflammatory markers, augmentation index (AIx), central pulse pressure and central systolic blood pressure in apparently healthy subjects. Design and settings An observational study conducted at a university teaching hospital. Methods and results Apparently healthy subjects (n = 158; 75 males, 83 females) passed a complete history and physical examination, blood tests and pulse wave analysis. AIx was significantly higher in patients with hsCRP levels above 1 mg/l (24.5 ± 9.9 versus 18.1 ± 12.6%, P < 0.001). Central pulse pressure and central systolic blood pressure were significantly higher in the group with hsCRP levels above 1 mg/l. No differences between groups were shown for peripheral pulse pressure, peripheral blood pressures and estimated aortic pulse wave velocity. In multiple regression analysis, AIx correlated positively with age, female gender, short stature, mean arterial pressure, hsCRP (P = 0.026) and white blood cell count (P = 0.01), and negatively with heart rate. Conclusions This study shows that plasma levels of hsCRP are positively correlated with AIx, central pulse pressure and central systolic blood pressure. Apparently healthy subjects with increased inflammatory markers have increased systemic arterial stiffness, which might reflect early atherosclerotic changes. Our results suggest that hsCRP and non-invasively measured arterial stiffness could serve as additional tools, beside conventional cardiovascular risk factors, for assessment of global arterial risk and preclinical atherosclerotic changes in arteries.

The association between hyperglycaemia on admission and 180-day mortality in acute myocardial infarction patients with and without diabetes.

Aim  To evaluate the association between hyperglycaemia on admission, previously known diabetes and 180‐day mortality in acute myocardial infarction (AMI) patients.

Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein

Objective Ageing, plasma circulating C-reactive protein (CRP), oxidized low-density lipoprotein (OxLDL) and homocysteine (Hcy) are associated with atherosclerosis. The aim of this study was to evaluate the relationship between age, inflammatory and oxidative stress-related markers with functional and structural changes of the arteries in asymptomatic persons. Methods CRP, OxLDL and Hcy were measured in 175 clinically healthy subjects, aged 40–70 years. Ultrasonography and pulse wave analysis were used to measure carotid intima–media thickness (IMT) and augmentation index (AIx). Results OxLDL was correlated with IMT (r = 0.24, P = 0.003), whereas CRP was correlated with AIx (r = 0.21, P = 0.005). No correlation was detected between Hcy and AIx or age-adjusted IMT. There was a significant association between AIx and age ≤50 years (r = 0.33; P = 0.001) and between IMT and age > 50 years (r = 0.40; P = 0.001). In stepwise regression analysis age, weight, white blood cell count, OxLDL, heart rate and timing of the reflected waveform adjusted for height were significantly and independently associated with IMT (R2 = 0.41; P < 0.001). At the same time, AIx as the dependent variable correlated positively with age, gender, CRP and mean arterial pressure, and negatively with heart rate, weight and height, in stepwise regression analysis (R2 = 0.63; P < 0.001). Conclusion The results of the present study showed that CRP, OxLDL, Hcy and age are not similarly related to AIx and IMT in asymptomatic persons. The results suggest that CRP and younger age are related to arterial stiffness, whereas OxLDL and older age become more important determinants of structural changes of the arteries in asymptomatic persons.

Inflammation and oxidative stress are associated differently with endothelial function and arterial stiffness in healthy subjects and in patients with atherosclerosis

Inflammation and oxidative stress (OxS) play key roles in atherogenesis; however, their causal relationship is not yet completely understood. Much attention has been given to the possibility that inflammation is a primary process of atherosclerosis and that OxS may be a by‐product of the inflammatory process. We hypothesized, accordingly, that chronic systemic inflammation affects endothelial vasomotor function in the subclinical condition, whereas oxidative modifications are more involved in the structural stiffening of the arteries in atherosclerosis. The aim of our study was to test this hypothesis. Endothelial function and arterial stiffness were assessed non‐invasively by pulse wave analysis, and blood/urinary samples were taken in 39 patients with peripheral arterial disease as well as in 34 controls. The patients showed significantly reduced endothelial function index (EFI) and increased augmentation index (AIx), as well as higher estimated aortic pulse wave velocity (PWV) and elevated values of the intercellular adhesion molecule‐1 (ICAM‐1), high sensitivity C‐reactive protein, myeloperoxidase and urinary 8‐iso‐prostaglandin F2a (F2‐IsoPs). There was an inverse association between EFI and ICAM‐1 (R = −0.44, p = 0.009) in the controls, but not in the patients. Augmentation index and estimated aortic PWV correlated with F2‐IsoPs only in the patients (R = 0.5, p = 0.001; R = −0.43, p = 0.006, respectively). After controlling for potential confounders, these associations remained significant. The study demonstrates that impairment of endothelial vasomotor capacity is affected by degree of inflammation in the subclinical condition, whereas arterial stiffening is determined by level of oxidative modifications in atherosclerosis.

Evidence for Oxidative Stress in Essential Hypertension: Perspective for Antioxidant Therapy

Background Despite therapy, arterial hypertension continues to be a risk factor of coronary artery disease (GAD). The role of oxidative stress, an important source of vascular injury, in the genesis of this increased risk also needs to be defined, because several antihypertensive drugs have demonstrated antioxidant effects. This study tested the existence of oxidative stress in young (<40 years) untreated patients with uncomplicated essential hypertension (EH). Methods Lipid peroxidation (LP) products (diene conjugates, basal and Fe-stimulated levels of thiobarbituric acid reactive substances) were detected spectrophotometrically in serum together with markers of antioxidant status (serum antioxidative capacity (AOC), red blood cell (RBC) glutathione) in 32 patients with mild-to-moderate EH and in 26 matched normotensive controls. Results All LP products were elevated (P < 0.01), while serum AOC was decreased (P < 0.001) and RBC glutathione increased (P < 0.05) in EH patients compared with controls. The presence of hypercholesterolaemia was not found to influence the differences in the measured parameters between hypertensive patients and controls significantly. Conclusions The results indicate that oxidative stress occurs in young patients with uncomplicated EH. Therefore antihypertensive treatment, especially in patients whose vascular disease is still reversible, should provide antioxidant protection.

Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension.

Objective To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients. Methods Forty-nine middle-aged patients with untreated stage I–II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 μmol/l was considered significant. Results Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 μmol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied. Conclusion: Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.

Oxidative stress and hyperinsulinaemia in essential hypertension : Different facets of increased risk

Objective To evaluate oxidative stress markers in normo and hyperinsulinaemic essential hypertension patients, and to relate these parameters to plasma glucose and insulin levels. Methods Diene conjugates, thiobarbituric acid reactive substances, iron-stimulated thiobarbituric acid reactive substances and anti-oxidative capacity of serum were detected in 32 untreated essential hypertension patients with normal glucose tolerance, divided into hyperinsulinaemic (n=12, fasting plasma insulin level >13.5 mU/I, means 2SD of controls) and normo-insulinaemic (n=20) subgroups, compared with 26 age- and body mass indexmatched controls. Plasma glucose and insulin levels were measured during an oral glucose tolerance test Results Levels of lipid peroxidation products (diene conjugates, thiobarbituric acid reactive substances and iron-stimulated thiobarbituric acid reactive substances) were elevated and serum anti-oxidative capacity decreased both in hyper- and in normo-insulinaemic patients compared with those in controls, with no significant differences between the hypertensive subgroups. No independent correlations were detected between oxidative stress markers and fasting or stimulated plasma insulin and glucose levels. The essential hypertension patients were characterized by a lower fasting glucose: insulin ratio and enhanced plasma insulin response to oral glucose test compared with controls. Conclusions The results suggest that oxidative stress occurs, in addition to disturbances in glucose metabolism, in essential hypertension patients, thus potentially exposing them to increased risk of developing complications. Factors other than plasma insulin level are likely to contribute to oxidative stress in hypertensive patients with normal glucose tolerance.

Effect of low-dose aspirin on the markers of oxidative stress.

Summary. The present study estimates effects of low-dose enteric coated aspirin (ECA) on oxidative stress (OS) markers in a group of middle-aged men (mean age 51.2 ± 6.9 years) free of pre-existing ischemic heart disease.Methods. Serum products of lipid peroxidation, and measures of antioxidative status were detected in 25 healthy men in baseline and after two-week treatment period.Results. In respect to serum products of lipid peroxidation and markers of antioxidant status, no statistically significant differences between the pre- and after-treatment data were observed for any measures, with the exception of values of serum antioxidative capacity (39.0 ± 2.5 and 42 ± 4.6, respectively).Conclusions. Administration of ECA does not initiate the OS in blood and improves the general antioxidative potency of blood. This may imply towards certain antiatherogenic influence of low-dose ECA, exhibited even with a short-term treatment period. Regarding OS markers, a variety of individual responses observed in the selected subgroups should be investigated and possibly taken into account while treatment with ECA is initiated for primary prevention of cerebrovascular events.

Association between arterial elasticity, C-reactive protein and maximal oxygen consumption in well-trained cadets during three days extreme physical load: a pilot study

Regular aerobic training has beneficial effects on inflammatory pathways and on arterial elasticity, which are both important cardiovascular risk factors. The aim of the present study was to evaluate the effect of extreme physical load on arterial elasticity and inflammatory markers in well-trained healthy men who participated in a high-ranking combat course. Seven well-trained male cadets were examined during an international military combat course of 3.5 days duration. Small (C2) and large (C1) artery elasticity was assessed using diastolic pulse wave analysis. Inflammatory markers and arterial elasticity measurement were performed before and after the competition. The extreme prolonged physical load caused individually different responses in arterial elasticity, C-reactive protein (CRP) and creatine kinase in individual cadets. Maximal oxygen consumption (VO(2) max kg(-1)) correlated significantly with the change (Delta-difference between baseline and 24 h recovery period) of creatine kinase (r= -0.78; p=0.04) and DeltaC2 (r=0.78; p=0.04) and DeltaC1 (r=0.82; p=0.02). In multivariate analysis (R(2)=0.89, p=0.01) the DeltaC2 correlated strongly with VO(2) max kg(-1) (p=0.005) and with the DeltaCRP (p=0.03), whereas the DeltaC1 correlated only with VO(2) max kg(-1) and did not correlate significantly with the DeltaCRP. Changes in small arterial elasticity induced by extreme physical load were significantly related to VO(2) max kg(-1) and DeltaCRP, whereas the change of large artery elasticity was only associated with VO(2) max kg(-1). Our preliminary results indicate that acute exercise-induced inflammation may affect small artery elasticity. However, further, more extensive studies are needed in this area.

Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects

Arterial stiffening may be linked to the reduced bioactivity of nitric oxide (NO) and increased plasma concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). The aim of this study was to investigate whether large (C1) and small artery (C2) elasticity is associated with endothelial function index (EFI) and plasma concentration of ADMA. We included 63 healthy subjects, aged 19 to 70 years, in the study. EFI, C1 and C2 were assessed by pulse wave analysis (PWA) and ADMA level was measured using an enzyme‐linked immunoassay. Linear regression analysis revealed significant positive correlation between EFI and both C1 and C2 (R = 0.29, p = 0.02; R = 0.38, p = 0.002, respectively). A significant inverse association occurred between ADMA and C1 as well as C2 (R = −0.32, p = 0.03; R = −0.37, p = 0.009, respectively). In multiple regression analysis, C2 was determined by EFI, ADMA, age and BMI, and C1 was correlated with EFI, age and BMI. These findings suggest that endothelial vasodilatory dysfunction and accumulation of ADMA may be important mechanisms underlying reduced arterial elasticity in healthy subjects.