C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease.

C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1beta, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(-511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(-174) and IL-6(-572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311-0.574) for CT or TT genotypes compared with 0.240 (0.107-0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l(-1), respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115-0.388) for carriers and 0.421 (0.290-0.552) for non-carriers (CRP 1.79 and 2.64 mg l(-1), respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients.

[Interventional cardiology in Latvia from 1993 to 2003]. / Invasive Kardiologie in Lettland von 1993 bis 2003.

A nationale programme for combatting cardiovascular diseases is being implemented in Letvia. A milestone was reached in 1993 with the establishment of a Letvian Centre for Cardiology. Within 10 years the only cardiac catheterization unit in the country has developed into a centre of excellence. But to meet the cardiological needs for all of Letvia requires at least three additional units for left heart catheterization and one for paediatric a cardiac catheterization.

Immune activation and degradation of tryptophan in coronary heart disease.

BACKGROUND: Inflammation and immune activation appear to be important in the pathogenesis of coronary heart disease (CHD). Cytokine interferon-gamma, which is released during cell-mediated immune responses, induces indoleamine (2,3)-dioxygenase (IDO), an enzyme degrading tryptophan to kynurenine. Therefore, immune stimulation is commonly associated with an increased kynurenine to tryptophan ratio (kyn trp-1) indicative for activated indoleamine (2,3)-dioxygenase and a measurable decline of tryptophan. METHODS: Blood concentrations of kynurenine and free tryptophan and the kynurenine to tryptophan ratio were examined in 35 patients with coronary heart disease verified by coronary angiography and compared with healthy controls. Patients were observed before percutaneous transluminal coronary angioplasty (21 patients: one with artery disease, nine with 2- or 3-artery disease, and five with restenosis). RESULTS AND CONCLUSIONS: Decreased tryptophan concentrations were found in a significant proportion of coronary heart disease patients and coincided with increased kyn trp-1 and also with increased neopterin concentrations, indicating an activated cellular immune response. We conclude that in coronary heart disease immune activation is associated with an increased rate of tryptophan degradation and thereby lowered tryptophan levels. Results may provide a basis for a better understanding of the pathogenesis of mood disturbances and depression in coronary heart disease patients.

The adjunctive effect of telmisartan in patients with hypertension uncontrolled on current antihypertensive therapy.

This prospective, double-blind, randomised, parallel-group, multicentre study assessed the adjunctive effect of telmisartan monotherapy versus placebo in controlling blood pressure during the last six hours of the 24-hour dosing period. After a two-week run-in phase, 375 patients with essential hypertension uncontrolled on existing therapy were randomised to either placebo or telmisartan (40 mg uptitrated to 80 mg after four weeks, if needed) for eight weeks. Ambulatory blood pressure monitoring (ABPM) was conducted at randomisation (baseline) and treatment end. The change from baseline in diastolic blood pressure (DBP) over the last six hours (primary endpoint) was significantly greater with telmisartan than placebo (adjusted mean treatment difference in favour of telmisartan: -3.7 mmHg, 95% confidence interval (CI) -5.5, -1.9 mmHg, p < or = 0.001, n = 350), as was the reduction in 24-hour DBP (adjusted mean treatment difference: -5.0 mmHg, 95% CI -6.5, -3.5 mmHg, p < or = 0.001). Telmisartan also reduced mean systolic blood pressure significantly more than placebo over the last six hours and the entire 24-hour dosing interval. Responder rates (ABPM DBP, seated DBP, and overall [seated SBP/DBP]) at 8 weeks were significantly higher with telmisartan than with placebo (p < or = 0.01). All treatments were well tolerated. When added to existing antihypertensive regimens, telmisartan offers additional effectiveness while maintaining placebo-like tolerability.

Plasma HDL-cholesterol has an effect on nitric oxide production and arachidonic acid metabolism in the platelet membranes of coronary heart disease patients without LDL-hypercholesterolemia.

AIM: To evaluate nitric oxide (NO) production and [3H]arachidonic acid (AA) incorporation into platelet membranes of coronary artery disease (CAD) patients with/without HDL-hypocholesterolemia. MATERIAL: 16 healthy controls (C), 14 CAD patients with plasma HDL-hypocholesterolemia (nCAD) and 14--without HDL-hypocholesterolemia (nCAD). All subjects were without peripheral vascular disease and hypertension. The groups were matched for age, sex, BMI. The diagnosis of CAD was substantiated by coronary angiography. METHODS: Nitric oxide end products xNO (NO2- plus NO3-) levels in the platelet membranes were measured using anion-exchange chromatography. [3H]AA release from labelled platelets was studied by the method of Neufeld and Majerus; radioactivity was measured by liquid scintillation counting. Levels of plasma HDL-cholesterol (HDL-Ch) and triglycerides were enzymatically determined. RESULTS: Significant increase (mean +/- SD; Mann-Whitney U test) of [3H]AA incorporation into platelet membrane phospholipids was noted in CAD patients in comparison with healthy subjects (p < 0.001). A correlation (multiple regression analysis) was established between HDL-C level and [3H]AA (r = -0.58, p < 0.05, n = 28); and between HDL-Ch and NOx levels (r = 0.76, p < 0.05, n = 28) in CAD patients. CAD patients had lower NOx than healthy subjects (p < 0.0001), NOx was lower in the group with decreased HDL-Ch concentration (wCAD 36 +/- 5 vs. nCAD 42.3 +/- 6 mumol/mg, p < 0.002). CONCLUSIONS: CAD patients show decreased ability to produce platelet-derived NO that leads to higher platelet sensitivity to aggregating stimuli. Decreased plasma HDL-Ch may affect AA metabolism and NO production in the platelet membranes of CAD patients without LDL-hypercholesterolemia.

The development of coronary insufficiency during prolonged treatment of essential hypertension.

The occurrence of signs of coronary insufficiency during prolonged combined treatment of essential hypertension was analysed in a selected group of 42 patients with left ventricular myocardial hypertrophy. During a four-year antihypertensive therapy 17% of patients developed angina pectoris on effort myocardial infarction occurred in 7%, and ischaemic ECG changes during bicycle ergometry or transoesophageal atrial pacing were detected in 36%. In the subgroup with an insufficient hypotensive effect and sustained severe myocardial hypertrophy the signs of coronary insufficiency occurred in 53%. Nevertheless, the attainment of a stable pressure normalization and regression of myocardial hypertrophy does not exclude the development of coronary insufficiency, even in patients treated with beta-adrenoblocking drugs.