Biomedical subjects

Terho Lehtimäki

Publications and source records attributed to Terho Lehtimäki.

At least 19 recordsLinked to original sources

PubMed2007

Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not associated with response to electroconvulsive therapy in major depressive disorder.

The aim of the present study was to examine an association of brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study group consisted of 119 patients consecutively admitted for ECT in the Department of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic criteria of DSM-IV for MDD. ECT was administered three times a week with a brief pulse constant current device. The Montgomery and Asberg Depression Rating Scale (MADRS) was used as an outcome measure of depression. Genotyping was performed using fluorescent allele-specific TaqMan probes. No association between either G196A or C270T and the response to ECT was found in the whole population. There were no significant differences in responses between men and women or between psychotic and non-psychotic patients. However, within subgroups such as in psychotic and in late-onset depression CC genotype of C270T may predict good response. BDNF may not be associated with response to ECT in general, but some association in subgroups may exist.

Age of Onset↗

PubMed2006

A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.

BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects. METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg), atorvastatin (40 mg), or placebo. PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05), while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1) in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.

Atorvastatin↗

PubMed2006

Tryptophan hydroxylase 1 gene (TPH1) moderates the influence of social support on depressive symptoms in adults.

BACKGROUND: Tryptophan hydroxylases (TPHs) are involved in the biosynthesis of serotonin and are therefore candidate genes for psychiatric disorders, including depression. We examined whether the common 218 A > C and 779 A > C polymorphisms in the tryptophan hydroxylase 1 gene (TPH1) moderated the association between perceived social support and sub-clinical depressive symptoms in adults. METHODS: The subjects were a randomly selected subsample (n=341) of individuals participating in the Cardiovascular Risk in Young Finns study, who had data on social support on one assessment time and depressive symptoms on two assessment times. Social support was assessed on the Perceived Social Support Scale Revised (PSSS-R) and depressive symptoms on a modified version of the Beck's Depression Inventory (BDI). RESULTS: We found that low social support predicted depressive symptoms more strongly in individuals carrying A alleles of the TPH1 than in others. The interaction effect was observed in a cross-sectional analysis and when predicting depressive symptoms over a four-year period. LIMITATIONS: We did not have data on TPH2, which has recently been identified as the primary TPH isomorphism affecting serotonin synthesis in the brain. CONCLUSIONS: TPH1 gene may be involved in the development of depressive symptoms by moderating the impact of depressogenic social influences.

Adult↗

PubMed2006

Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia.

The aim of this study was to investigate the relationship between the functional C957T single-nucleotide polymorphism of the dopamine D2 receptor (DRD2) gene and the risk for schizophrenia. We therefore conducted a case-control association study of 188 Finnish schizophrenia patients meeting the DSM-IV criteria and 384 healthy controls. The 5' nuclease assay (TaqMan) was used to determine genotypes. A greater proportion of patients with schizophrenia than healthy controls were C-allele carriers (odds ratio 1.5, 95% confidence interval (CI) 1.0-2.3, P=0.05). Our results are in agreement with an earlier association study suggesting that the C957T C-allele plays a role in the genetic vulnerability for schizophrenia and support the involvement of the DRD2 gene in schizophrenia pathogenesis.

Adult↗

PubMed2006

Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidance.

We conducted a series of tests to determine whether there is any association between tryptophan hydroxylase 1 (TPH1) and temperament in adulthood. In addition to testing for main effects, we investigated whether TPH1 gene variation modifies the influence of childhood environment on temperament in adulthood. The subjects were 341 healthy adults whose childhood environment was assessed by their mothers in 1980 and who self-rated their temperaments twice, in 1997 and 2001. We found no association between the TPH1 gene and temperament; however, among women, the TPH1 gene modified a relationship between adverse childhood environment and harm avoidance in adulthood. This finding was confirmed in the same sample in another test setting 4 years later. The presence of the A/A haplotype of the TPH1 intron 7 A218A and A779C polymorphism predicted a high level of adulthood harm avoidance in the presence of a hostile childhood environment as defined in terms of emotional rejection, maternal neglect and harsh and inconsistent discipline. In addition, the findings suggest a gene-environment correlation for novelty seeking in men.

Adolescent↗

PubMed2006

Age-dependent association between hepatic lipase gene C-480T polymorphism and the risk of pre-hospital sudden cardiac death: the Helsinki Sudden Death Study.

OBJECTIVE: We investigated the association between hepatic lipase (HL) C-480T polymorphism and the risk of acute myocardial infarction (AMI) as well as pre-hospital sudden cardiac death (SCD). METHODS: Seven hundred sudden or unnatural pre-hospital deaths of middle-aged (33-70 years, mean 53 years) Caucasian Finnish men were subjected to detailed autopsy (Helsinki Sudden Death Study). Genotype data were obtained for 682 men. RESULTS: In logistic regression analysis with age, body mass index, hypertension, diabetes, smoking and alcohol consumption as covariates, men with the TT genotype had an increased risk for SCD and AMI compared to CC carriers (OR=3.0, P=0.011; and OR=3.7, P=0.003). There was a significant age-by-genotype interaction (P<0.05) on the risk of SCD. Compared to CC genotype carriers, the association between the TT genotype and SCD was particularly strong (P=0.001) among men <53 years of age, but this association was non-significant among older men. This was mainly due to a strong association between the TT genotype and AMI due to severe coronary disease in the absence of thrombosis. Carriers of the TT genotype were more likely to have severe coronary stenoses (> or =50%) than men with the CT or CC genotype (P=0.019). CONCLUSIONS: The results suggest that HL C-480T polymorphism is a strong age-dependent risk factor of SCD in early middle-aged men.

Adult↗

PubMed2006

Prediction of coronary artery disease by transesophageal echocardiographic detection of thoracic aortic plaque in patients with chronic kidney disease.

BACKGROUND/AIMS: Our aim was to examine the significance of thoracic aortic plaque detected by transesophageal echocardiography (TEE) in the prediction of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). METHODS: We examined 118 patients (mean age 52 +/- 12 years) with CKD and followed them for a mean of 3.4 +/- 0.8 years. The study group included 52 predialysis patients with moderate to severe CKD (plasma creatinine > or = 200 micromol/l), 32 patients on dialysis treatment, and 34 renal transplant recipients. At baseline, TEE was performed to evaluate thoracic aortic atherosclerosis. CAD was defined by a history of a documented myocardial infarction, a coronary angiogram or a post-mortem autopsy finding showing significant occlusive CAD by the end of the follow-up period. RESULTS: CAD was documented in 31 (26%) of the 118 study patients. The presence of thoracic aortic plaque had a sensitivity of 100% and a specificity of 37% for CAD and the positive and negative predictive values were 36 and 100%, respectively. In the subset of 36 patients with morphological findings of coronary arteries by angiogram or autopsy, the presence of large thoracic aortic plaques (> or = 3 mm in diameter) had a 73% sensitivity and 90% specificity for significant coronary artery stenosis. The positive and negative predictive values were 95 and 56%, respectively. CONCLUSION: TEE may be used for detecting high-risk patients with CKD; the absence of thoracic aortic plaque predicted the absence of CAD, and the presence of large aortic plaques predicted significant coronary artery stenosis.

Adult↗

PubMed2006

Relations of APOE promoter polymorphisms to LDL cholesterol and markers of subclinical atherosclerosis in young adults.

The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females.

Adolescent↗

PubMed2006

The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality.

BACKGROUND: The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile--using genetic, haemodynamic and electrocardiographic (ECG) markers--of individuals at high risk of cardiovascular diseases, events and deaths. METHODS AND DESIGN: All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications. DISCUSSION: FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers.

Cardiovascular Diseases↗

PubMed2006

Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects. METHODS: Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA. RESULTS: Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels. CONCLUSIONS: There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.

Adult↗

PubMed2006

Gene expression profiles in Finnish twins with multiple sclerosis.

BACKGROUND: Since genetic alterations influencing susceptibility to multiple sclerosis (MS), the most common autoimmune demyelinating disease of the central nervous system (CNS), are as yet poorly understood, the purpose of this study was to identify genes responsible for MS by studying monozygotic (MZ) twin pairs discordant for MS. METHODS: In order to identify genes involved in MS development, the gene expression profiles in blood mononuclear cells obtained from eight MZ twin pairs discordant for MS were analyzed by cDNA microarray technology detecting the expression of 8 300 genes. The twins were collected from the Finnish Twin Cohort Study and both affected subjects and their healthy siblings underwent neurological evaluation and cerebral and spinal magnetic resonance imaging. Gene expressions were confirmed by relative quantitative reverse transcription PCR. RESULTS: It appeared that 25 genes were at least two-fold up-regulated and 15 genes down-regulated in 25% (2/8) of twins with MS when compared to their healthy siblings. Moreover, 6/25 genes were up-regulated in 40% of MS twins and one gene, interferon alpha-inducible protein (clone IFI-6-16) (G1P3), in 50% of them. The six most constantly expressed genes are (1) G1P3, (2) POU domain, class 3, transcription factor 1, (3) myxovirus resistance 2, (4) lysosomal-associated multispanning membrane protein-5, (5) hemoglobin alpha 2 and (6) hemoglobin beta. CONCLUSION: Over two-fold up-regulation of these six genes in almost half of MZ twins with MS suggests their role in MS pathogenesis. Studies using MZ MS twins obtained from genetically homogeneous population offer a unique opportunity to explore the genetic nature of MS.

Diseases in Twins↗

PubMed2006

Cholesterol absorption and synthesis in pediatric kidney, liver, and heart transplant recipients.

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.

Adolescent↗

PubMed2006

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes.

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-D-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 +/- 2.0%) and high (17.4 +/- 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level (P = 0.012) and muscle (P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake (P = 0.040) and glucose extraction rate (P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 (P < 0.05) and lower coronary flow reserve (P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

Biomarkers↗

PubMed2006

Polymorphism of the angiotensin-converting enzyme (ACE) and angiotesinogen (AGT) genes and their associations with blood pressure and carotid artery intima media thickness among healthy Finnish young adults--the Cardiovascular Risk in Young Finns Study.

The roles of angiotensin converting enzyme (ACE) insertion-deletion (I/D) and angiotensinogen (AGT) m235t polymorphisms in cardiovascular diseases have been investigated extensively during the past decade but results have been inconsistent. A sex-specific association between the ACE I/D polymorphism and systolic blood pressure (BP) was seen among Finnish children and adolescents previously. We investigated if these polymorphisms associate with the BP and carotid artery intima media thickness (IMT) in the same cohort during their adulthood. IMT data were available for 224 ACE I/D genotyped individuals and 202 AGT m235t genotyped individuals. Systolic and diastolic blood pressure values did not differ between ACE and AGT genotypes. Age and BMI adjusted mean IMT was 0.02 (95% CI: -0.05 to 0.02, p=0.33) and 0.03 mm (95% CI: -0.07 to 0.001, p=0.06) lower among the ID and DD genotype groups, respectively, compared to the II genotype group. MT and TT genotype groups had 0.02 mm (95% CI: -0.01 to 0.05, p=0.17) higher and 0.01 mm (95% CI: -0.04 to 0.02, p=0.59) lower mean IMT, respectively, compared to the MM genotype group. We conclude that ACE I/D and AGT m235t polymorphisms are not associated with carotid IMT in healthy young Finnish adults.

Adult↗

PubMed2006

The p22phox C242T gene polymorphism is associated with a reduced risk of angiographically verified coronary artery disease in a high-risk Finnish Caucasian population. The Finnish Cardiovascular Study.

BACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion, which may play an important role in the development of atherosclerosis and coronary artery disease (CAD). The p22phox, a component of the NADPH oxidase, is essential for the activation of this enzyme, and intensive expression of the p22phox has been reported in human atherosclerotic arteries. However, studies on the association of the C242T polymorphism in the p22phox gene with CAD have produced conflicting results, and the relation of this polymorphism with CAD is not well known in a population with acquired risk factors enhancing the NADPH-dependent superoxide production. METHODS: As part of the Finnish Cardiovascular Study, a case-control study was conducted with 402 high-risk Finnish Caucasian patients undergoing coronary angiography. Genotyping was performed using the 5' nuclease TaqMan assay. RESULTS: The prevalence of the T allele (TT + TC genotypes) was significantly lower among angiographically verified CAD patients (n = 250) than among control subjects (n = 152, P = .013). In contrast to subjects with the CC genotype, the T allele was found protective against CAD (odds ratio = 0.531, 95% CI 0.331-0.852, P = .009), and the results remained significant after adjustment for other significant coronary risk factors. CONCLUSIONS: The T allele in the C242Tpolymorphism of the p22phox gene had a protective effect against the development of CAD despite the exposure of study subjects to risk factors related to excessive NADPH-dependent superoxide production.

Adult↗

PubMed2006

Asymmetric dimethylarginine and hemodynamic regulation in middle-aged men.

The goal of this study was to evaluate the role of asymmetric dimethylarginine (ADMA) in the regulation of hemodynamic functions in hypertensive men. It has been suggested that ADMA, as an endogenous nitric oxide synthase inhibitor, is linked to hypertension and vascular reactivity. Sixty-seven men aged 51.1 years (range, 45-55 years) were studied. Plasma ADMA and symmetric dimethylarginine were determined by high-performance liquid chromatography-tandem mass spectrometry. Blood pressure (BP) was measured by 24-hour ambulatory recordings and casual measurements. Hemodynamic regulation was assessed by noninvasive methods. The nitric oxide production was estimated based on plasma nitrate (NO(3)(-)) determination. Results showed that plasma arginine derivatives or l-arginine/ADMA ratio was not associated with BP values observed during 24-hour monitoring or in casual measurements. Systemic vascular resistance, pulse wave velocity, or cardiac output was not associated with plasma ADMA or plasma NO(3)(-) levels. No association was found between plasma ADMA and NO(3)(-) either. Interestingly, subjects on antihypertensive treatment had lower plasma ADMA concentrations than nontreated subjects (0.30+/-0.08 and 0.36+/-0.11 micromol/L, respectively, P=.04) despite higher BP values. In conclusion, these results suggest that plasma ADMA does not have a determinative role in the regulation of hemodynamic functions in Finnish middle-aged men.

Arginine↗

PubMed2006

Apolipoprotein E polymorphism and changes in serum lipids during a family-based counselling intervention.

OBJECTIVE: To compare serum lipids and their changes during a family-based health education in children aged 6-17 years with or without the epsilon4 allele of the gene encoding apolipoprotein E (apoE). DESIGN: An intervention study. SETTING: A family-based prevention of risk factors of coronary heart disease in Eastern Finland. The programme consisted of two counselling meetings at children's schools and three at children's homes. SUBJECTS: Four hundred and thirty-nine children with a family history of cardiovascular diseases (CVD) participated in a family-based health education. The children were divided into two groups according to apoE genotype. The risk group consisted of 143 children having apoE epsilon4 allele (genotype epsilon3/4 or epsilon4/4) and the non-risk group of 296 children without apoE epsilon4 allele (epsilon2/3 or epsilon3/3). The final sample of the follow-up study included 354 (81%) children (114 and 240, respectively). RESULTS: Baseline differences were found in low-density lipoprotein cholesterol (LDL-C) (P=0.007) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (P=0.030) among boys and in total cholesterol (TC)/HDL-C (P=0.008) and LDL-C/HDL-C ratios (P=0.006) among girls. Differences between groups in changes during the follow-up were observed only for TC/HDL-C ratio (P-value adjusted for age=0.049) among boys. CONCLUSIONS: At baseline, children with apoE epsilon4 allele had on average a more unfavourable lipid profile than those without apoE epsilon4 allele. However, the effect of about 33 months' family-based health education on plasma lipids did not depend on apoE genotype in children with a family history of CVD.

Adolescent↗

PubMed2006

Determinants of short-term variation in arterial flow-mediated dilatation in healthy young men.

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

Adult↗