Showing papers by "Tomi Laitinen published in 2008"

Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: The Cardiovascular Risk in Young Finns Study

Abstract: Aims The objective was to produce reference values and to analyse the associations of age and sex with carotid intima-media thickness (IMT), carotid compliance (CAC), and brachial flow-mediated dilatation (FMD) in young healthy adults. Methods and results We measured IMT, CAC, and FMD with ultrasound in 2265 subjects aged 24–39 years. The mean values (mean ± SD) in men and women were 0.592 ± 0.10 vs. 0.572 ± 0.08 mm ( P < 0.0001) for IMT, 2.00 ± 0.66 vs. 2.31 ± 0.77%/10 mmHg ( P < 0.0001) for CAC, and 6.95 ± 4.00 vs. 8.83 ± 4.56% ( P < 0.0001) for FMD. The sex differences in IMT [95% confidence interval (CI) for sex difference −0.013 to 0.004 mm, P = 0.37] and CAC (−0.01 to 0.18%/10 mmHg, P = 0.09) became non-significant after adjustments with risk factors and carotid diameter. In FMD, the sex difference was unaltered after adjustments for risk factors, but was reversed after adjustment with brachial diameter (95% CI 0.18–1.32%, P < 0.01). With aging, IMT increased 5.7 ± 0.4 µm/year and CAC decreased 0.042 ± 0.003%/10 mmHg/year. The association of age with IMT and CAC was slightly attenuated (12 and 22%, respectively) after adjustments with risk factors, but remained significant (both P < 0.0001). Aging was not significantly related to brachial FMD ( P = 0.16). Conclusion Reference values produced in the present study can be utilized in the cardiovascular risk stratification among young people. Sex differences in the markers of subclinical atherosclerosis were mostly explained by differences in risk factors and vessel size. This emphasizes the importance of risk factor control in the prevention of atherosclerosis in young adults.

Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation.

Abstract: BACKGROUND Normal pregnancy is associated with enhanced vasodilatation because of the increased nitric oxide (NO) production. Because L-homoarginine can act as a substrate for NO production, concentrations of L-homoarginine in normal pregnancy were assessed in the present study to test whether L-homoarginine is associated with endothelial function. METHODS AND RESULTS Healthy non-pregnant (n=61) and pregnant women (n=58) were studied in a cross-sectional study. L-homoarginine, L-arginine, asymmetric dimethylarginine and symmetric dimethylarginine concentrations were determined simultaneously by high-performance liquid chromatography. Endothelium-dependent brachial artery flow-mediated dilation (FMD) was measured by ultrasound. The serum L-homoarginine concentration was significantly higher during the second and the third trimesters compared with the levels in the non-pregnant women (4.8+/-1.7 and 5.3+/-1.5 vs 2.7+/-1.0 micromol/L, p<0.001, respectively). In line with this, FMD increased in response to pregnancy (p<0.05). Three months after delivery, the L-homoarginine concentrations and FMD were comparable to those recorded in the non-pregnant females. The concentration of L-homoarginine correlated significantly with gestational age (r=0.426, p=0.001) and brachial artery diameter and FMD (r=0.362, p=0.006 and r=0.306, p=0.022, respectively) in pregnancy. CONCLUSIONS L-homoarginine appears to be increased during the second and third trimesters of pregnancy and may contribute to the enhanced endothelial function in normal pregnancies.

Electrocardiographic alterations during hyperinsulinemic hypoglycemia in healthy subjects.

Abstract: Background: We evaluated the arrhythmogenic potential of hypoglycemia by studying electrocardiographic (ECG) changes in response to hyperinsulinemic hypoglycemia and associated sympathoadrenal counterregulatory responses in healthy subjects. Methods: The study population consisted of 18 subjects, aged 30–40 years. Five-minute ECG recordings and blood samplings were performed at baseline and during the euglycemic and hypoglycemic hyperinsulinemic clamp studies. PR, QT, and QTc intervals of electrocardiogram and ECG morphology were assessed from signal-averaged ECG. Results: Although cardiac beat interval remained unchanged, PR interval decreased (P < 0.01) and QTc interval (P < 0.001) increased in response to hyperinsulinemic hypoglycemia. Concomitant morphological alterations consisted of slight increases in R-wave amplitude and area (P < 0.01 for both), significant decreases in T-wave amplitude and area (P < 0.001 for both), and moderate ST depression (P < 0.001). Counterregulatory norepinephrine response correlated with amplification of the R wave (r =−0.620, P < 0.05) and epinephrine response correlated with flattening of the T wave (r =−0.508, P < 0.05). Conclusions: Hyperinsulinemic hypoglycemia with consequent sympathetic humoral activation is associated with several ECG alterations in atrioventricular conduction, ventricular depolarization, and ventricular repolarization. Such alterations in cardiac electrical function may be of importance in provoking severe arrhythmias and “dead-in-bed” syndrome in diabetic patients with unrecognized hypoglycemic episodes.

Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Abstract: Background— Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD). Methods and Results— We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher ( P <0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age ( P =0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P =0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort ( P =0.521). Conclusions— The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.

Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study

Abstract: Aims To study the relations between the metabolic syndrome (MS) and subclinical atherosclerosis in young adults. Methods and results International Diabetes Federation (msIDF), National Institute of Health Adult Treatment Panel III (msNCEP), and European Group for the Study of Insulin Resistance (msEGIR) definitions of MS were related to carotid artery intima–media thickness (cIMT), brachial flow-mediated dilatation (FMD), and carotid artery compliance (CAC) in 2163 Finnish adults (aged 32 ± 5years). All definitions associated with increased cIMT and decreased CAC in both sexes. The cIMT values (mean±SD) were 0.576 ± 0.088 mm in subjects without the syndrome, 0.615 ± 0.102 mm in msIDF, 0.617 ± 0.104 mm in msNCEP, and 0.607 ± 0.097 mm in msEGIR ( P < 0.0001). Corresponding CAC values were 2.26 ± 0.72, 1.76 ± 0.66, 1.73 ± 0.66, 1.72 ± 0.66%/10 mmHg ( P < 0.001). Impaired brachial FMD was not related to MS but it modified the relations between MS and cIMT: MS correlated with increased cIMT in subjects with an impaired FMD response ( P = 0.003) but not in subjects with an enhanced FMD response ( P = 0.75). Conclusion All current definitions of MS identify a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis.

Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies

Abstract: The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P < 0.01 to <0.001), while pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are unlikely to account for pregnancy-related increased flow-mediated dilatation

Abstract: Summary Background: Our objective was to investigate whether serum concentrations of asymmetric dimethylarginine (ADMA) or l-arginine correlate to hyperlipidemia or endothelial function in normal pregnancy compared with the non-pregnant subjects. Methods and results: As a part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we examined 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and ADMA, symmetric dimethylarginine (SDMA) and l-arginine were determined concomitantly with endothelium-dependent brachial artery flow-mediated dilation (FMD), measured by ultrasound. All serum lipid concentrations were significantly higher in pregnant women than in non-pregnant women (P < 0·001 for each). The mean serum ADMA concentration in pregnant women was significantly lower compared with the non-pregnant controls (0·513 μmol l−1 ± 0·0593 versus 0·577 μmol l−1 ± 0·0710, P < 0·001). Lowered ADMA concentrations did not correlate statistically to FMD in these healthy pregnant women but FMD was enhanced towards the end of pregnancy. Conclusions: ADMA and l-arginine concentrations fall in normal pregnancy despite marked hypercholesterolemia. Endothelium-dependent vasodilation is enhanced in normal pregnancy but is not statistically correlated to maternal serum ADMA or l-arginine concentrations.