Tiina Ristimäe

Heart rate dynamics in patients with stable angina pectoris and utility of fractal and complexity measures

Dynamic analysis techniques may uncover abnormalities in heart rate (HR) behavior that are not easily detectable with conventional statistical measures. However, the applicability of these new methods for detecting possible abnormalities in HR behavior in various cardiovascular disorders is not well established. Conventional measures of HR variability were compared with short-term (< or = 11 beats, alpha1) and long-term (> 11 beats, alpha2) fractal correlation properties and with approximate entropy of RR interval data in 38 patients with stable angina pectoris without previous myocardial infarction or cardiac medication at the time of the study and 38 age-matched healthy controls. The short- and long-term fractal scaling exponents (alpha1, alpha2) were significantly higher in the coronary patients than in the healthy controls (1.34 +/- 0.15 vs 1.11 +/- 0.12 [p <0.001] and 1.10 +/- 0.08 vs 1.04 +/- 0.06 [p <0.01], respectively), and they also had lower approximate entropy (p <0.05), standard deviation of all RR intervals (p <0.01), and high-frequency spectral component of HR variability (p <0.05). The short-term fractal scaling exponent performed better than other heart rate variability parameters in differentiating patients with coronary artery disease from healthy subjects, but it was not related to the clinical or angiographic severity of coronary artery disease or any single nonspectral or spectral measure of HR variability in this retrospective study. Patients with stable angina pectoris have altered fractal properties and reduced complexity in their RR interval dynamics relative to age-matched healthy subjects. Dynamic analysis may complement traditional analyses in detecting altered HR behavior in patients with stable angina pectoris.

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.

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.

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.

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.

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.

Nesiritiid – uus võimalus südamepuudulikkuse ravis

Nesiritiid on inimese BNP rekombinantne vorm, mille aminohapete jarjestus on samasugune nagu endogeensel BNP-l ja farmakoloogiline toime ei erine endogeensest BNPst. Nesiritiidraviks sobivad koige paremini niisugused sudamepuudulikkusega haiged, kellel on vedeliku ulekoormus ja korge tsentraalne vererohk. Nesiritiid on vastunaidustatud kardiogeense soki puhul ja haigetel, kelle sustoolne arteriaalne vererohk on Eesti Arst 2004; 83 (1): 51-53

Projekt “Aterogeensuse staatuse skriinimine Eesti rahvastikul” (ASSER): uudne käsitlusviis südame- ja veresoonkonnahaiguste preventsioonis

Sudame- ja veresoonkonnahaiguste haigestumuse, suremuse ja ravikulude vahendamise voimalust nahakse eelkoige elustiili muutmises ja olemasolevate ravivoimaluste ning preventsiooniprogrammide paremas kasutamises. Artiklis on tutvustatud projekti, mille eesmark on uudse kasitlusviisi propageerimine ja aterogeensete haiguste patogeneesi, ravi ning preventsioonivoimaluste tapsem selgitamine ning sobivaimate uuringute leidmine varajase aterogeneesi soeluuringuks. Eesti Arst 2003; 82 (1): 29–34

Aspiriin südame-veresoonkonnahaiguste sekundaarses preventsioonis

Aspiriini antiagregatiivne toime on seotud tema voimega mojutada tsukliliste prostanoidide ja teiste prostaglandiinide biosunteesi. Lisaks sellele on aspiriinil ka antioksudatiivsed ja poletikuvastased omadused. Aspiriin pidurdab ateroskleroosi arengut ning parandab endoteeli funktsiooni aterosklerootilises veresoones. Sudamelihase infarkti podemise jarel on 15–20% haigetel risk jargneva 2–5 a jooksul surra voi haigestuda korduvasse infarkti. Aspiriin annuses 81–325 mg paevas on efektiivne sudame isheemiatovega haigetel valtimaks sekundaarseid tromboemboolseid tusistusi. Eesti Arst 2003; 82 (8): 561–566

Heart rate variability in patients with the first and recurrent myocardial infarction.

Impairment of heart rate variability (HRV) has been reported in patients after myocardial infarction (MI). However, it is currently unknown whether the similar alterations of autonomic profile that accompany the first MI will evolve after a recurrent MI. Forty male outpatients with a previous first MI (group I) and 20 age-matched male patients with a recurrent MI (group II) were studied and measures of HRV were estimated from 24-hour electrocardiograms. In comparison with group I, group II had significantly higher values of ratio of low-to high-frequency power (6.9±5.7 vs 3.7±1.8, respectively, p<0.05), and a tendency to lower values of all other measures of HRV. We conclude our study indicates that in comparison to group I, group II demonstrated augmented sympathetic drive as assessed by the indices of HRV. The shift toward adrenergic predominance detected after recurrent MI may result from altered afferent feedback from abnormally contracting left ventricular segments to the autonomic modulation of sinus node, or accompany subclinical state of heart failure not readily accessible with hemodynamic measurements.