-
[show abstract]
[hide abstract]
ABSTRACT: This study aimed at investigating whether cardiovascular risk factors and their impact on total risk estimation differ between men and women.
Cross-sectional cohort study.
Finnish cardiovascular risk subjects (n = 904) without established cardiovascular disease, renal disease, or known diabetes.
Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular risk using SCORE risk charts.
According to the SCORE risk charts, 27.0% (95% CI 23.1-31.2) of the women and 63.1% (95% CI 58.3-67.7) of the men (p < 0.001) were classified as high-risk subjects. Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency.
The SCORE system does not take into account cardiovascular risk factors typical in women, and thus underestimates their total cardiovascular risk. Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment. especially in women.
Scandinavian journal of primary health care 06/2012; 30(2):101-6. · 2.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase blood pressure (BP) and potentially reduce the efficacy of several antihypertensive drugs. We evaluated the effect of low-dose acetylsalicylic acid (ASA) on BP control in drug-treated hypertensive patients in a primary care population.
Nine hundred and five successive patients aged 25–91 years (mean 65.5 years) from 15 health centers in south-west Finland were studied. The patients were on antihypertensive monotherapy (45.7%) or on combination therapy (54.3%). Office BP was measured twice with a 2-min interval after at least a 10-min rest using an ordinary sphygmomanometer.
Patients receiving ASA (n = 246) showed lower diastolic BP (83.9 ± 9.0 vs. 87.0 ± 9.6 mmHg; P < 0.001) compared with those who were not using any NSAIDs (n = 659). No significant difference in systolic BP was observed between the groups. As a result, pulse pressure was slightly higher in the ASA group (66.9 ± 18.9 vs. 63.3 ± 17.7 mmHg, P = 0.01). Mean arterial pressure was lower in the ASA group (106.2 ± 10.6 vs. 108.1 ± 10.4 mmHg, P = 0.02). In a stepwise linear multivariate model, ASA remained a significant predictor of lower diastolic BP even after the adjustment with the confounding effects of age and sex.
According to our population-based study low-dose ASA does not have deleterious effects on BP control in drug-treated hypertensive patients.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 02/2011; 18(1):136-40. · 2.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown.
In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle-brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System.
The prevalence of PAD (defined as ABI < or =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P < 0.001).
Subclinical PAD is common in hypertensive patients even without comorbidities. The measurement of ABI is an efficient method to identify patients with increased cardiovascular risk and worth performing to hypertensive patients, particularly those with pulse pressure above 65 mmHg. Uniform criterions of defining PAD and borderline PAD would aid physicians in clinical decision-making.
Journal of hypertension 07/2009; 27(10):2036-43. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to clarify whether treatment of hypertension and concomitant risk factors in Finland has improved after the introduction of national evidence-based guidelines for antihypertensive treatment in 2002. Changes in the other cardiovascular risk factors of the Finnish hypertensive patients were also assessed.
Nationwide questionnaire survey of consecutive hypertensive patients having met by general practitioners during a given week in autumn 2006.
Finnish general practice offices in primary care.
Data from 715 hypertensive patients, 358 men and 357 women, from 72 general practice offices.
Systolic and diastolic blood pressure, serum lipids, smoking status and information about other risk factors.
The mean blood pressure of the patients was 147/88 mmHg. Eighty-one men (23%) and 85 women (24%) reached the treatment goal of 140/85 mmHg or less. Low-density lipoprotein-cholesterol level below 2.5 mmol/l was reached by 104 (29%) men and 104 (29%) women. Only 13% of the hypertensive patients (16.8% of the men and 9.2% of the women) were active smokers.
Roughly three-quarters of hypertensive patients still failed to reach the blood pressure target of 140/85 mmHg recommended by the current Finnish Hypertension Guidelines. Our results are disappointing, considering the homogenous Finnish population and thorough primary healthcare system. Although the mean serum cholesterol concentration of the hypertensive population exceeded target values set by the guidelines, a clear improvement compared with early 21st century is seen. Also smoking has diminished considerably.
Blood pressure 02/2009; 18(1-2):62-7. · 1.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The blood pressure-lowering mechanism of low-sodium diet is not fully understood.
We assessed the effects of salt restriction on cardiac parasympathetic function as measured by heart-rate variability (HRV) in mild to moderate hypertensive patients. Eighty patients were randomized to a 6-month low- (N = 40) or normal (N = 40) sodium diet and a 24-h electrocardiogram (ECG) was carried out in the beginning of the study and at 6 months. Five time-domain and six frequency-domain HRV variables were analyzed: mean RR interval, standard deviation of normal RR intervals, mean of the standard deviations of all RR intervals for 5-min segments of the entire recording, percentage of differences between adjacent normal RR intervals exceeding 50 ms, square root of the mean of squared differences between adjacent normal RR intervals, total (0.01-0.40 Hz), high frequency (HF, 0.15-0.40 Hz), low frequency (LF, 0.04-0.15 Hz), very LF (0.01-0.04 Hz) and LF/HF ratio.
Although blood pressure diminished significantly (systolic blood pressure (SBP) from 149.9 +/- 14.7 mm Hg to 130.3 +/- 11.8 mm Hg, P < 0.001 and diastolic blood pressure (DBP) from 98.0 +/- 6.4 mm Hg to 87.1 +/- 6.2 mm Hg, P <0.001) after 6 months in the salt reduction group, no significant differences in the change between the groups could be detected.
A moderate, prolonged dietary sodium restriction does not alter HRV. Therefore, mechanisms other than cardiac autonomic mechanisms are likely to predominate in the blood pressure-lowering effect of salt restriction.
American Journal of Hypertension 10/2008; 21(11):1183-7. · 3.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The gastrointestinal (GI) safety of different non-steroidal anti-inflammatory drugs (NSAIDs) in a real-life setting remains ill defined. The aim of this study was to examine the risk of upper GI events associated with various NSAIDs in a general population.
A nationwide, register-based, matched case-control study was carried out in outpatient residents of Finland in 2000-04. Cases with upper GI events (n=9191) were drawn from the Hospital Discharge Register and individually matched to controls (n=41,780) from the Population Register.
The semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, etodolac) had the highest odds ratio for upper GI events even after adjusting for various potential confounders (adjusted odds ratio (AOR) 3.63; 95% CI 3.08-4.28), followed by non-selective (2.98; 2.70-3.29) and COX-2 selective NSAIDs (2.53; 2.09-3.07). When the current use of semi-selective NSAIDs was compared with that of non-selective and COX-2 selective NSAIDs, the AORs were 1.54 (1.13-2.09) and 1.67 (1.10-2.53), respectively. The AORs for the use of COX-2 selective NSAIDs did not differ statistically from the non-selective NSAIDs (AOR 0.92; 0.65-1.31). The AORs for individual NSAIDs varied across and within categories.
As a group, the GI safety of the COX-2 selective NSAIDs was not demonstrated as definitively superior to non-selective NSAIDs. Semi-selective NSAIDs do not seem to offer any GI advantage over other NSAIDs.
Scandinavian Journal of Gastroenterology 09/2007; 42(8):923-32. · 2.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Atherosclerosis 11/2006; 188(2):391-7. · 3.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the risk of first myocardial infarction (MI) associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs) in the general population.
We conducted a population-based matched case-control study over the years 2000-3 in outpatient residents of Finland. In the nationwide Hospital Discharge Register 33 309 persons with first time MI were identified. A total of 138 949 controls individually matched for age, gender, hospital catchment area, and index day were selected from the Population Register. For combined NSAIDs, the adjusted odds ratio for the risk of first MI with current use was 1.40 (95% CI, 1.33-1.48). The risk was similar for conventional (1.34; 1.26-1.43), semi-selective (etodolac, nabumetone, nimesulide, and meloxicam) (1.50; 1.32-1.71), and cyclo-oxygenase-2 (COX-2) selective NSAIDs (rofecoxib, celecoxib, valdecoxib, and etoricoxib) (1.31; 1.13-1.50). Age of current user did not consistently modify the risk. No NSAID was associated with an MI-protective effect. All durations from 1 to 180 days of conventional NSAIDs and from 31 to 90 days duration of COX-2 selective NSAIDs were associated with an elevated risk of MI.
Current use of all NSAIDs is associated with a modest risk of first time MI.
European Heart Journal 08/2006; 27(14):1657-63. · 10.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to compare home and ambulatory blood pressure (BP) in the adjustment of antihypertensive treatment.
After a 4-week washout period, patients whose untreated daytime diastolic ambulatory BP averaged > or = 85 mm Hg were randomized to be treated according to their ambulatory or home BP. Antihypertensive treatment was adjusted at 6-week intervals according to the mean daytime ambulatory diastolic BP or the mean home diastolic BP, depending on the patient's randomization group. If the diastolic BP stayed above 80 mm Hg, the physician blinded to randomization intensified hypertensive treatment.
Ninety-eight patients completed the study. During the 24-week follow-up period both systolic and diastolic BP decreased significantly within both groups (P < .001). At the end of the study, the systolic/diastolic differences between ambulatory (n = 46) and home (n = 52) BP groups in home, daytime ambulatory, night-time ambulatory, and 24-h ambulatory BP changes averaged 2.6/2.6 mm Hg, 0.6/1.7 mm Hg, 1.0/1.4 mm Hg, and 0.6/1.5 mm Hg, respectively (P range .06 to .75) A nonsignificant trend to more intensive drug therapy in the ambulatory BP group and a nonsignificant trend to larger share of patients reaching (57.7% v 43.5%, P = .16) the target pressure in the home BP group was observed due to the 3.8 mm Hg difference in ambulatory and home diastolic BP at randomization.
The adjustment of antihypertensive treatment based on either ambulatory or home BP measurement led to good BP control. No significant between-group differences in BP changes were seen at the end of the study. Additional research is needed to provide more conclusive results.
American Journal of Hypertension 06/2006; 19(5):468-74. · 3.18 Impact Factor
-
Reijo Laaksonen,
Karin M Thelen,
Hannu Päivä,
Jussi Matinheikki, Risto Vesalainen,
Tuula Janatuinen,
Juhani Knuuti,
Riikka Rontu,
Klaus von Bergmann,
Dieter Lütjohann,
Terho Lehtimäki
[show abstract]
[hide abstract]
ABSTRACT: 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.
Atherosclerosis 04/2006; 185(1):206-9. · 3.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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).
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).
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.
European Journal of Clinical Pharmacology 01/2006; 62(1):9-14. · 2.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
American Journal of Hypertension 12/2005; 18(11):1415-20. · 3.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: International guidelines have given diverse recommendations as to which side of the stethoscope should be used in the measurement of blood pressure.
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.
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.
Department of Medicine, Turku University Central Hospital.
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.
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.
Journal of Hypertension 04/2005; 23(3):499-503. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Molecular Medicine 01/2005; 82(12):821-5. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
International Journal of Cardiology 12/2004; 97(2):317-8. · 7.08 Impact Factor
-
Terho Lehtimäki,
Reijo Laaksonen,
Tuula Janatuinen, Risto Vesalainen,
Pirjo Nuutila,
Kari Mattila,
Erkki Ilveskoski,
Mari Luomala,
Pekka Saikku,
Juhani Knuuti,
Mikko Hurme
[show abstract]
[hide abstract]
ABSTRACT: 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.
Pharmacogenetics 10/2003; 13(10):633-9.
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Vascular Medicine 01/2003; 8(3):185-9. · 1.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Molecular Medicine 12/2002; 80(12):802-7. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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).
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.
Journal of Nuclear Medicine 06/2002; 43(6):773-9. · 6.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Biomedical Science 11(1):59-64. · 2.01 Impact Factor
