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 = 0.40; 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 (R = 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 (R = 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.

The relationship between inflammation and arterial stiffness in patients with essential hypertension.

BACKGROUND: Data about the correlation between augmentation index (AIx), timing of the reflected waveform (T(r)) and inflammatory markers in patients with essential hypertension are not yet well established. The aim of this study was to compare plasma high-sensitivity C-reactive protein (hsCRP), white blood cell count and fibrinogen in hypertensive patients and in normotensive controls and to assess the relationship between inflammatory markers and arterial stiffness. METHODS: Forty-two healthy middle-aged patients with untreated stage I-II essential hypertension and 42 sex- and age-matched controls were recruited in the study. Pulse wave analysis was used to assess AIx and T(r). RESULTS: Plasma hsCRP, white blood cell count, AIx and T(r) were significantly higher in the patients with essential hypertension. In multiple regression analysis, AIx correlated positively with age, female gender, mean arterial pressure and log(hsCRP), and negatively with heart rate and height (R(2)=0.75, p<0.001). T(r) correlated negatively with log(hsCRP) (r=-0.34, p=0.002) for the whole study group. However, after adjusting for mean arterial pressure, age, height, heart rate and sex to the regression model, no correlation was revealed between log(hsCRP) and T(r) (p=0.35) as the dependent variable (R(2)=0.48, p<0.001). CONCLUSIONS: Untreated hypertensive patients with low or moderate total cardiovascular risk had significantly increased blood hsCRP and white blood cell count and arterial stiffness, expressed as AIx and T(r). AIx correlated independently with hsCRP in multiple regression analysis. Measurement of arterial stiffness and inflammation can be suggested as an additional tool to assess cardiovascular risk in hypertensive patients with low or moderate total cardiovascular risk as estimated by traditional risk factors.

Effects of amlodipine and candesartan on oxidized LDL level in patients with mild to moderate essential hypertension.

OBJECTIVE: To compare the effects of amlodipine and candesartan on oxidized low-density lipoprotein (OxLDL), conjugated dienes (CD) and baseline diene conjugation in circulating low-density lipoproteins (LDL-BDC) level during antihypertensive treatment. METHODS: Forty-nine patients with untreated mild to moderate essential hypertension were recruited in a randomized double-blind study to receive a daily dose either of 8 mg candesartan or 5 mg amlodipine for 16 weeks. Blood pressure, OxLDL, CD, LDL-BDC, triglycerides (TG), total cholesterol and lipoprotein cholesterol were measured at baseline, at week 2 and at week 16. RESULTS: During treatment, in addition to a significant decrease in systolic and diastolic blood pressure, high level of OxLDL decreased significantly reaching practically upper kit reference values. Both treatment groups were similar with regard to the studied parameters at all time points. At the same time serum TG, lipoprotein and total cholesterol levels as well as LDL-BDC did not change and CD levels did not exceed endemic normal. Decrease in both systolic and diastolic blood pressure was associated with decrease in LDL-BDC/LDL. CONCLUSIONS: Besides their antihypertensive effects, both candesartan and amlodipine are efficient drugs for reducing OxLDL level, being neutral with regard to serum lipids.

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 micromol/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 micromol/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.

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.

Homocysteine and red blood cell glutathione as indices for middle-aged untreated essential hypertension patients.

OBJECTIVE: Intracellular glutathione in its reduced state is a principal cellular biomolecule with antioxidant activity. Glutathione and homocysteine metabolism are closely associated. As both oxidative stress and hyperhomocystinemia are associated with hypertension, we assessed the relationships between these variables. DESIGN AND SETTING: An observation-based case-control study, performed at a university teaching hospital. PATIENTS: Middle-aged male patients with untreated uncomplicated essential hypertension (mean +/- standard deviation age 53.0 +/- 7.2 years, n = 48) before any treatment and controls with similar age distributions (age 51.6 +/- 5.5 years, n = 28) were evaluated. METHODS: In all subjects, the plasma levels of homocysteine, lipids, creatinine, protein, and glucose were measured. Reduced and oxidized glutathione and folic acid were measured from red blood cells (RBC). RESULTS: The hypertensive patients had decreased levels of red blood cell reduced glutathione (RBC-GSH) and increased levels of oxidized glutathione, which resulted in elevated ratio of oxidized/reduced glutathione as compared to controls (P < 0.001). Plasma homocysteine levels were significantly higher in the hypertensive patients versus the age-matched controls (P < 0.004). In the hypertensive patients, RBC-GSH correlated inversely with systolic blood pressure, serum creatinine, protein and RBC folic acid. No correlation was detected between RBC-GSH and homocysteine. In the controls, RBC-GSH correlated inversely with homocysteine, RBC folic acid and creatinine. According to multiple regression, in the hypertensive patients RBC-GSH was related to systolic blood pressure, hemoglobin, plasma homocysteine, creatinine and protein. Such a relationship was not detected for the controls. CONCLUSION: In untreated hypertensive patients both homocysteine and systolic blood pressure are associated with intracellular oxidative stress as determined by RBC-GSH.