PubMed Health⌕ Search

Biomedical subjects

Risto Vesalainen

Publications and source records attributed to Risto Vesalainen.

13 recordsLinked to original sources
PubMed2005

Effect of pravastatin on plasma sterols and oxysterols in men.

OBJECTIVES: The HMG-CoA reductase inhibitors, or statins, are well established in the prevention and treatment of coronary artery disease, mainly by lowering low-density lipoprotein (LDL) cholesterol levels. These compounds are structurally similar, but differ in their lipophilicity. Several studies have indicated a link between cholesterol and Alzheimer's disease (AD), and there is also epidemiological evidence that statin treatment may decrease the prevalence of dementias. In the present study we wanted to investigate whether pravastatin treatment affects brain cholesterol metabolism. METHODS: A post hoc analysis was performed with plasma material from a clinical trial where 51 healthy men (35+/-4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Cholesterol, its precursor lathosterol, its brain-specific metabolite 24(S)-hydroxycholesterol (24S-OH-chol) and 27-hydroxycholesterol (27-OH-chol) were determined in plasma samples before and after treatment by using gas-liquid chromatography (GC)-flame ionization detection (GC-FID) and GC mass spectrometry (GC-MS). RESULTS: Besides reducing total cholesterol (-20%, P<0.001) and LDL cholesterol (LDL-C; -33%, P<0.001) concentrations, pravastatin treatment resulted in a decrease of the ratio of lathosterol to cholesterol, a surrogate marker of endogenous cholesterol synthesis, by 20% (P<0.05). Absolute concentrations of 24S-OH-chol were not altered, but its ratio to cholesterol slightly increased by 15% (P<0.05). 27-OH-chol concentrations as well as its ratio to cholesterol were both significantly altered due to pravastatin treatment (-7% and +14%, P<0.05 for both, respectively). CONCLUSIONS: The treatment with pravastatin 40 mg once a day for 6 months does not affect brain cholesterol metabolism as judged by plasma concentrations of 24(S)-hydroxycholesterol.

Adult↗
PubMed2005

The influence of hepatic lipase C-480T polymorphism on coronary flow reserve in young men is independent of the plasma cholesterol level.

BACKGROUND: The hepatic lipase (HL) gene C-480T promoter polymorphism affects gene transcription and enzyme activity and leads to CC, CT, and TT genotypes. Recently, HL expression was detected in macrophages. It has been postulated that HL might have a direct role in the pathogenesis of atherosclerosis without changes in the plasma profile. We hypothesized that the difference of plasma cholesterol level may not influence the effect of HL genotype on coronary reactivity. METHODS: A total of 108 young men (aged 34+/-5 years) were genotyped and divided into three groups. These groups contained 45, 49 and 14 men having either normal (4.9+/-1.2 mmol/L), mildly (5.5+/-0.8 mmol/L) or severely (7.8+/-1.9 mmol/L, subjects with familial hypercholesterolemia) elevated mean plasma cholesterol level, respectively. Myocardial blood flow (MBF) was measured at rest and during adenosine or dipyridamole-induced hyperemia with positron emission tomography using [(15)O] H(2)O. RESULTS: The effect of HL genotype on the indices of MBF was parallel within all cholesterol groups and therefore they were combined. In all subjects, basal flow did not differ between the genotypes. However, men with CC genotype had a significantly higher hyperemic blood flow (3.86+/-1.26 mLg(-1)min(-1) versus 3.20+/-1.38 mLg(-1)min(-1), p=0.007), higher coronary flow reserve (CFR, 4.80+/-1.77 versus 3.77+/-1.43, p=0.001) and lower coronary resistance during hyperemia (25.63+/-9.98 mmHg min g mL(-1) versus 35.00+/-23.95 mmHg min g mL(-1), p=0.003) than T allele carriers. In multivariate regression analysis, after adjustment for age, body mass index, serum lipids, blood pressure, adenosine or dipyridamole administration, and study group, HL polymorphism was an independent predictor of blood flow during hyperemia (p=0.016), coronary resistance (p=0.014), and CFR (p=0.005), respectively. CONCLUSIONS: The HL C-480 T polymorphism is associated with CFR, which is an early indicator of atherosclerosis, independently of the level of plasma cholesterol in young men.

Adenosine↗
PubMed2005

Genetic variant of the SREBF-1 gene is significantly related to cholesterol synthesis in man.

Sterol regulatory element binding proteins-1 and -2 (SREBPs) are transcription factors controlling lipid homeostasis in human cells. The G-allele carriers of the SREBF-1 gene C-G polymorphism in exon 18c and coding for glycine at the protein level (G952G) have shown to associate more frequently with obesity and type 2 diabetes than the C-allele carriers. However, the C-allele has suggested to be linked to dyslipidemia. Thus, our aim was to study effect of the SREBF-1 gene polymorphism (G952G) on sterol metabolism in man. Ninety-five subjects with moderate hypercholesterolemia participated in this study and 14 homozygous CC carriers of the SREBF-1 (G952G) gene were found. Plasma lathosterol concentration and lathosterol-to-cholesterol ratio, markers of endogenous cholesterol synthesis, were significantly higher in CC homozygous subject compared to others. Similarly muscle cholesterol (p=0.045) and lathosterol (p=0.054) concentrations were elevated in the CC homozygotes supporting the view that endogenous cholesterol synthesis rate is SREBF-1 genotype-dependent.

Adult↗
PubMed2005

Self-monitoring of blood pressure promotes achievement of blood pressure target in primary health care.

BACKGROUND: The majority of hypertensive patients do not reach the target blood pressure (BP). We sought to clarify whether intermittent self-monitoring of BP leads to better BP control compared to ordinary treatment in general practice. METHODS: Two hundred sixty-nine hypertensive patients participated in this multicenter, randomized, parallel-group study in primary health care. Home BP was measured in the self-monitoring (SM) group at 0, 2, 4, and 6 months, and in the control (C) group at 0 and 6 months. The participating physicians were instructed to intensify the antihypertensive therapy when needed. RESULTS: At the beginning, both groups had similar home BP levels (SM 143.1 +/- 17.4/85.3 +/- 7.4 mm Hg v C 143.9 +/- 18.3/85.4 +/- 7.5 mm Hg). After 6 months, there were significant decreases in systolic (P <or= .0001), diastolic (P <or= .0029), and pulse pressures (P <or= .021) in both groups. Systolic (-7.8 +/- 13.1 mm Hg v -4.5 +/- 12.2 mm Hg, P = .047) and pulse pressure (-4.7 +/- 9.0 mm Hg v -2.2 +/- 10.0 mm Hg, P = .042) decreased significantly more than in the self-monitoring group. The decrease in diastolic pressure was similar in both groups (SM -3.1 +/- 6.2 mm Hg v C -2.3 +/- 8.3 mm Hg, P = not significant). The patients in the SM group reached home BP target more often than those in the C group (29% v 16%, P = .016). There was a nonsignificant trend toward lower office BP values in the SM group. CONCLUSIONS: Self-monitoring decreased systolic and pulse pressure significantly more than ordinary treatment and promoted achievement of target BP. This was most likely due to improved patient compliance and more active treatment by the physicians. Our results suggest that home measurement is useful in the control of hypertension.

Adult↗
PubMed2005

Bell or diaphragm in the measurement of blood pressure?

BACKGROUND: International guidelines have given diverse recommendations as to which side of the stethoscope should be used in the measurement of blood pressure. OBJECTIVE: To determine if there is any difference between the bell and the diaphragm sides of the ordinary acoustic stethoscope in the measurement of blood pressure. DESIGN AND METHODS: We compared, in random order, the bell and the diaphragm side of the ordinary acoustic stethoscope and also the effect of low- and high-frequency amplification with an electronic stethoscope in the measurement of blood pressure, in 250 adults. SETTING: Department of Medicine, Turku University Central Hospital. RESULTS: No statistically significant difference was seen between the bell side and the diaphragm side of the acoustic stethoscope, either in systolic blood pressure (SBP; mean +/- SD 129.5 +/- 21.7 and 129.4 +/- 20.8 mmHg, respectively) or diastolic blood pressure (DBP; 77.0 +/- 12.0 and 77.1 +/- 12.0 mmHg, respectively). Both the low-frequency (130.7 +/- 22.5 mmHg) and the high-frequency (131 +/- 22.2 mmHg) amplification of systolic Korotkoff sounds yielded significantly greater values of SBP than were measured either with the bell (P = 0.008 compared with low frequency, P = 0.0005 compared with high frequency) or the diaphragm (P = 0.004 compared with low frequency, P = 0.0001 compared with high frequency). Low-frequency amplification of DBP (76.4 +/- 12.3 mmHg) yielded values significantly lower than those measured with the bell (P = 0.04) or the diaphragm (P = 0.01). Values from high-frequency amplification of DBP (77.2 +/- 12.3 mmHg) did not differ significantly from those measured with the acoustic stethoscope. CONCLUSIONS: Both sides of the acoustic stethoscope give similar results in the measurement of office blood pressure and either side can be used in the reliable measurement of blood pressure.

Adult↗
PubMed2004

Estrogen receptor genotype modulates myocardial perfusion in young men.

Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor alpha (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [(15)O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allele. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes.

Adult↗
PubMed2004

The effect of mannan-binding lectin variant alleles on coronary artery reactivity in healthy young men.

Mannan-binding lectin (MBL) is a serum acute-phase protein and a complement component secreted by the liver. Its deficiency caused by point mutations in the MBL gene has recently been associated with severe atherosclerosis. In this study, we investigated the effect of MBL variant alleles on coronary artery reactivity, which is an early marker of coronary dysfunction and predicts the development of atherosclerosis and coronary artery disease. The study population consisted of 51 apparently healthy, normo- or mildly hypercholesterolemic young men. Myocardial blood flow was measured at baseline and during adenosine-induced hyperemia with positron emission tomography (PET), and MBL genotyping was performed using restriction fragment-length polymorphism. As a result, MBL variant alleles had no effect on coronary artery reactivity. This finding suggests that MBL deficiency is not an independent risk factor for coronary dysfunction and early atherogenic changes but rather a co-factor in the development of atherosclerosis. Thus, the connection of MBL variant alleles with environmental risk factors in atherosclerosis should further be assessed.

Adult↗
PubMed2003

Interleukin-1B genotype modulates the improvement of coronary artery reactivity by lipid-lowering therapy with pravastatin: a placebo-controlled positron emission tomography study in young healthy men.

A polymorphism at position -511 of interleukin-1B (IL-1B) gene promoter regulates IL-1B levels, immune and inflammatory responses and possible atherogenesis. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to this IL-1B polymorphism. The study comprised a randomized, double-blind, placebo-controlled trial with two treatment groups: (i) pravastatin (40 mg/day, n=14) and (ii) placebo (n=20) for 6 months (baseline mean cholesterol 5.5 +/- 0.8 mmol/l; age 35 +/- 4 years). Myocardial blood flow was measured by PET at rest and during adenosine infusion using 15O-labelled water. PET studies, lipid, IL-1beta and C-reactive protein analyses were performed at baseline and after 6 months of therapy. IL-1B genotype was determined by polymerase chain reaction. There were no differences between IL-1B allele 2 carriers (A2+) and non-carriers (A2-) in basal or adenosine-stimulated myocardial flow (ASMF), at baseline. Regarding the change in ASMF and coronary flow reserve, there was a significant IL-1B genotype-by-treatment group interaction (analysis of covariance, P=0.028 and P=0.002, respectively) during follow-up. In the pravastatin group, the ASMF increased by 18.0% in subjects with IL-1B A2- (n=7), but decreased by 2% in subjects with IL-1B A2+ (n=7). There were no significant changes from the baseline values in placebo recipients. After treatment, both genotype groups showed a similar decrease in serum total and low density lipoprotein cholesterol (P<0.0001 for both). In conclusion, coronary function improves after 6 months of pravastatin therapy in subjects with the IL-1B A2- allele but not in those with the IL-1B A2+ allele.

Adenosine↗
PubMed2003

Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults.

Elevated plasma levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are related to decreased myocardial vasodilatory capacity and increased risk of acute coronary events. As statin treatment is known to increase nitric oxide bioavailability and enhance myocardial function, we tested whether ADMA concentration modifies the effect of pravastatin on myocardial blood flow in young adults with mild hypercholesterolemia. Fifty-one men (35 +/- 4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Myocardial blood flow was measured at rest and during adenosine-induced hyperemia using positron emission tomography and oxygen-15-labeled water at baseline and after treatment. Plasma ADMA levels were assessed with high performance liquid chromatography. Low baseline plasma ADMA concentration (< median) predicted a significant improvement of adenosine-induced blood flow after statin intervention (baseline to follow-up change +35%, p = 0.004), whereas high baseline ADMA (> or = median) was associated with no increase in adenosine-induced flow.

Adenosine↗
PubMed2002

Endothelial nitric oxide synthase genotype modulates the improvement of coronary blood flow by pravastatin: a placebo-controlled PET study.

The objective was to study whether coronary blood flow or its response to pravastatin are affected by genetic variation in the endothelial nitric oxide synthase (eNOS) gene. Vascular endothelial nitric oxide maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. Its formation is catalyzed by eNOS, a constitutive enzyme, which has a polymorphic site in intron 4 (4a/b). Some clinical studies have suggested an association of the rare a-allele of eNOS with coronary artery disease and myocardial infarction. We carried out a double-blind placebo-controlled study involving 43 men (aged 35+/-4 years), who were randomized to receive either 40 mg/day pravastatin ( n=21) or placebo ( n=22) for 6 months. Myocardial blood flow was measured by positron emission tomography (PET) using (15)O-labeled water. PET was performed at rest and after stimulation by adenosine infusion. PET and lipid analyses were carried out at baseline and after 6 months. eNOS genotyping was done by PCR. At baseline there were no differences in basal or adenosine-stimulated coronary blood flow between subjects with either eNOS bb or ba genotypes. At the end of the study genotypes reacted differently between pravastatin and placebo groups with respect to the change in adenosine-stimulated flow (ANCOVA P=0.008). More specifically, after pravastatin treatment the adenosine-stimulated flow increased by 54.5% in men with the eNOS ba genotype, whereas in the men with the bb genotype no significant change in flow was observed ( P=0.002 for ba versus bb). In the placebo group there were no significant changes in blood flow from the baseline values ( P=0.916 for ba versus bb). After pravastatin treatment both genotype groups showed a similar decrease in serum total cholesterol and low-density lipoprotein cholesterol ( P<0.00001 for both). Our results suggest that adenosine-stimulated myocardial perfusion improves after treatment with pravastatin in subjects with the eNOS ba genotype but not in those with the bb genotype. This effect is not dependent on the decrease of serum cholesterol.

Adult↗
PubMed2002

Exercise training in chronic heart failure: beneficial effects on cardiac (11)C-hydroxyephedrine PET, autonomic nervous control, and ventricular repolarization.

UNLABELLED: Abnormalities of autonomic nervous function are associated with a poor prognosis of patients with chronic heart failure (CHF). We studied the effects of a 6-mo exercise training program on Q-T interval dispersion, heart rate and blood pressure variability, baroreflex sensitivity, myocardial blood flow (MBF), and presynaptic sympathetic innervation in 13 patients with New York Heart Association class II-III heart failure. METHODS: MBF was measured with the H(2)(15)O and C(15)O technique. Cardiac presynaptic innervation was studied by (11)C-hydroxyephedrine (HED) retention assessed with PET. Heart rate and blood pressure variability and baroreflex sensitivity were tested with the phenylephrine method. All studies were performed before and after a 6-mo exercise training program. The exercise capacity was determined by spiroergometry, and Q-T dispersion was measured from a standard 12-lead electrocardiogram. RESULTS: Q-T dispersion was reduced after the training period (mean +/- SEM, from 52 +/- 5 to 36 +/- 5 ms [P = 0.01]). Global (11)C-HED retention improved from 0.228 +/- 0.099 to 0.263 +/- 0.066 s(-1) (P < 0.05). Global MBF was not affected by training, but MBF increased in areas of low initial perfusion in patients with coronary artery disease (from 0.382 +/- 0.062 to 0.562 +/- 0.083 mL/g/min [P < 0.005]). The high-frequency spectrum and total R-R interval variability increased (from 4.53 +/- 0.30 to 5.02 +/- 0.36 ms(2) [P < 0.05] and from 3.60 +/- 0.34 to 4.31 +/- 0.37 ms(2) [P < 0.005], respectively). Both changes correlated significantly with the observed change in (11)C-HED retention. There was a significant reduction of total and a near-significant reduction of low-frequency (LF) systolic blood-pressure (SBP) variability (from 4.89 +/- 1.03 to 3.18 +/- 0.48 [P < 0.05] and from 2.79 +/- 0.38 to 1.76 +/- 0.24 [P = 0.059], respectively). The decrease in LF SBP variability correlated inversely with the enhancement of (11)C-HED retention (r = -0.66; P < 0.05). Baroreflex sensitivity increased from 5.83 +/- 0.82 to 10.15 +/- 1.66 ms/mm Hg (P < 0.05). CONCLUSION: Exercise training induces beneficial changes in functional and imaging measures of cardiovascular autonomic nervous control. These observations point to a training-induced shift toward normalization of the compensatory autonomic nervous imbalance in CHF.

Autonomic Nervous System↗
PubMedDate not supplied

Myeloperoxidase gene variation and coronary flow reserve in young healthy men.

Chronic inflammation may lead to endothelial dysfunction, which manifests as an impaired coronary reactivity. Impairment in coronary flow reserve (CFR), preceding the clinical symptoms of coronary artery disease, can be measured noninvasively by positron emission tomography. Myeloperoxidase (MPO) is an oxidative enzyme present in phagocytes and atherosclerotic lesions. The MPO gene has a promoter polymorphism (-463G/A) which affects gene transcription. Whether these variants associate with coronary artery function is not known. Myocardial blood flow at rest and during adenosine-induced hyperemia was assessed in 49 healthy young men with normal or slightly elevated serum total cholesterol. These subjects were divided into high (G/G) and low (A/G, A/A) MPO expression groups and effect of MPO genotype on myocardial blood flow was evaluated. We found a significant difference between MPO genotypes in CFR after adjusting for age, body mass index, smoking and family history of cardiovascular disease (p = 0.019). Men with G/G genotype had 18.1% lower CFR than subjects with low-expression genotypes (A/G and A/A). This was due to an 11.5% lower adenosine-stimulated flow of the G/G genotype carriers (p = 0.049). These findings provide evidence that MPO polymorphism is associated with coronary artery reactivity. However, the number of individuals investigated was low and our observation should be confirmed by a larger number of subjects.

Adenosine↗