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J Sinisalo

Publications and source records attributed to J Sinisalo.

7 recordsLinked to original sources
PubMed2007

Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease.

Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.

Adult↗
PubMed2000

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Aged↗
PubMed1999

Effects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls.

BACKGROUND AND HYPOTHESIS: Alcohol consumption may have advantageous epidemiologic effects but ethanol also increases the risk of sudden coronary death. Prolongation of QT interval has been reported in chronic alcoholics. Long QT period predisposes to serious arrhythmias, and therefore we studied whether acute alcohol intoxication prolongs repolarization in patients with stable coronary artery disease (CAD). METHODS: The effects of acute ethanol steady-state intravenous infusion (0.72 g/kg body weight within 60 min) on QT interval and QT dispersion, assessed by 12-lead electrocardiograms (ECG), were studied in 22 men with stable CAD and in 10 controls. Heart rate variability was measured by Holter recordings. RESULTS: Mean blood alcohol rose to 26.1 +/- 4.3 mmol/l(1.2 +/- 0.2/1000), and was maintained for 2 h. Heart rate was 56 +/- 7 beats/min before and 54 +/- 8 beats/min during ethanol infusion (NS). The heart rate-adjusted QT interval increased on the average 13-23 ms over the 12-lead ECG (p < 0.005). The QT dispersion remained unaltered. The was no difference in the repolarization response in the patients with CAD compared with the controls. The high- and low-frequency components of heart rate variability remained unaltered. CONCLUSIONS: In middle aged men, regardless of the presence of CAD, moderate amounts of alcohol cause prolongation of ventricular repolarization. Changes in the activity of the autonomic nervous system do not seem to explain the observed phenomenon.

Adult↗
PubMed1999

Ursodeoxycholic acid and endothelial-dependent, nitric oxide-independent vasodilatation of forearm resistance arteries in patients with coronary heart disease.

AIMS: Ursodeoxycholic acid (UDCA) has cholesterol lowering and anti-inflammatory effects and bile acids are reported to exert vasodilator effects; all of these properties might be considered desirable in a drug used in the treatment of patients with coronary heart disease. We investigated a hypothesis that UDCA may dilate arteries and the mechanism of action. METHODS: We evaluated effects of a 6-week treatment with UDCA in 11 coronary heart disease patients on endothelium-dependent (acetylcholine-induced) and -independent (nitroprusside-induced) vasodilatations in forearm vasculature by strain-gauge plethysmography. Healthy individuals (n=14) served as baseline controls. RESULTS: The percentage increase by acetylcholine in the flow of the infused arm relative to the non-infused arm of coronary heart disease patients during the trial remained unaltered, but vasodilatation to NG-monomethyl-l-arginine+acetylcholine was improved by 161+/-27% with UDCA vs 83+/-22% with placebo (mean difference 91% [95% CI 35%, 147%], P=0.016). CONCLUSIONS: Six weeks' UDCA therapy improved endothelium-dependent nitric oxide-independent vasodilatation, which might maintain arterial flow in coronary heart disease patients under conditions of impaired nitric oxide production.

Acetylcholine↗
PubMed1999

Endothelial release of tissue-type plasminogen activator and ischemia-induced vasodilatation are linked in patients with coronary heart disease.

Dysfunction in the vascular endothelium disturbs blood flow and predisposes individuals to atherosclerosis. Deteriorated fibrinolysis may further enhance the risk for atherothrombosis. We investigated 14 healthy volunteers and 24 patients with coronary heart disease. Endothelium-dependent (acetylcholine- and ischemia-induced) and endothelium-independent (nitroprusside-induced) vasodilatation in the forearm vasculature were studied using strain-gauge plethysmography, and the fibrinolytic system measured as the response of tissue plasminogen activator (t-PA) to provocation testing (20 min venous occlusion; VOT). When acetylcholine-induced vasodilatation was measured, endothelium-dependent vasodilatation differed between groups: those with coronary heart disease had a median value of 8.5 ml/min per 100 g tissue (25th to 75th percentile 4.8-10.3), compared with 11.6 ml/min per 100 g tissue (7.3-15.5) among healthy volunteers (P = 0.03). However, ischemia-induced vasodilatation showed no difference between the groups [26.8 (22.7-35.0) versus 29.1 (25.6-30.7) ml/min per 100 g tissue, respectively, NS]. Levels of t-PA after VOT also showed no difference between the groups [21.5 (16.5-31.9) versus 20.4 (11.8-31.5) ng/ml, respectively, NS]. Results of ischemia tests and levels of t-PA after VOT correlated only in patients with coronary heart disease (r = 0.5, P = 0.015), and not in healthy volunteers. We observed a positive correlation between endothelium-dependent vasodilatation function and endothelial release of t-PA. This indicates that the same mechanism that results in defective ischemia-induced endothelial relaxation in patients with coronary heart disease may also result in suppressed fibrinolytic capacity, thus making such patients more prone to atherothrombosis.

Adult↗
PubMed1998

The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production.

Chronic Chlamydia pneumoniae infection, characterized by elevated levels of C. pneumoniae IgG and IgA antibodies and immunocomplexes, is associated with myocardial infarction and angiographically verified coronary heart disease. C. pneumoniae organisms have also been found in coronary atheromas, but not in healthy vessels. We investigated the effect of 4 months' doxycycline therapy on serological markers of C. pneumoniae infection and coronary risk factors. Thirty-four non-smoking men, aged 57.9 (+/- 5.2) years, who had mild hypertension or moderate hypercholesterolaemia and a previous coronary bypass, were randomly assigned to receive doxycycline or matching placebo for 4 months. Acetylsalicylic acid and beta-blocker were the only other medications allowed. Patients were examined physically and by laboratory tests; their basal nitric oxide production was determined by blood flow responses to intra-arterial monomethyl-L-arginine at baseline and at 2 and 4 months. The tests were also taken at 6 months after medication. At entry, the demographic, clinical, blood flow and laboratory measurements were similar in both groups, with the exception of fibrinogen and triglyceride levels, which were higher in the placebo group. No significant changes were found in any of the parameters during the treatment. Thus extended doxycycline therapy did not affect C. pneumoniae antibodies or coronary heart disease risk factors. We conclude that doxycycline monotherapy may not be sufficient to eradicate chronic C. pneumoniae infection.

Adult↗