A comparison of secondary prevention practice in poststroke and coronary heart disease patients.

OBJECTIVES: It is evident that patients with atherosclerotic vascular disease (AVD) benefit from appropriate secondary prevention. In clinical reality, the secondary prevention in AVD patients other than those with coronary heart disease (CHD) is often overlooked. Therefore, we compared the adherence to secondary prevention principles between poststroke and CHD patients. STUDY DESIGN: Descriptive (cross-sectional) study with prospective mortality follow-up. METHODS: We examined 1729 chronic patients with AVD (mean age 65.9 (±SD 9.6) years), 964 with CHD, and 765 poststroke (pooled data of Czech samples of EUROASPIRE III, IV, and the ESH stroke survey). The interview was performed 6-36 months after the coronary event/revascularization or the first ischemic stroke, while the mortality follow-up 5 years after this interview. RESULTS: Poststroke patients had a significantly higher risk of persistent smoking, blood pressure ≥140/90 mmHg and LDL ≥2.5 mmol/L than CHD patients [odds ratios adjusted for age, gender and survey were 1.63 (95% CI: 1.13-2.33), 1.38 (95% CI: 1.13-1.69) and 2.26 (95% CI: 1.84-2.78), respectively]. In contrast, poststroke patients showed a lower risk of inappropriate glucose control and hypertriglyceridemia [0.66 (95%CI: 0.54-0.82) and 0.74 (95%CI: 0.61-0.91), respectively]. The prescription rates of antiplatelets/anticoagulants, antihypertensives and statins were also significantly lower in poststroke than in CHD patients (89.4 vs 93.7, 85.9 vs 97.5, and 57.7 vs 89.8, respectively). Mortality analysis was performed in a subsample of 815 subjects interviewed in 2006/07. The 5-year all-cause mortality rates were 25.8% and 13.3% in poststroke and coronary patients, respectively (P = 0.0023); the hazard ratio for stroke adjusted for major risk factors was 1.85 (95% CI: 1.31-2.63). CONCLUSIONS: Compared to CHD patients, poststroke patients are strongly handicapped in terms of poor adherence to secondary prevention target, prescription of basic pharmacotherapies and mortality risk.

Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population.

Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.

Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: consecutive survivors and population-based controls.

OBJECTIVE: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking. METHODS: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism. RESULTS: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype. CONCLUSIONS: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.

Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations.

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

[Distribution of lipoprotein associated phospholipase A2 in Czech population and its interaction with conventional cardiovascular risk]. / Distribuce s lipoproteiny asociované fosfolipázy A2 v ceské populaci a její interakce s konvencním kardiovaskulárním rizikem.

INTRODUCTION: Lipoprotein associated phospholipase A2 (Lp PLA2) represent new cardiovascular risk factor and potential treatment target. We aimed to analyze the epidemiological situation of this factor in Czech population. METHODS AND RESULTS: The study population consisted from 1 962 subjects, a random samples of general population (postMONICA study), and from patients with manifest coronary or cerebrovascular disease (Czech samples of EUROASPIRE III survey). Lp PLA2 activity was estimated using commercial kits by diaDexus Inc. in frozen samples. Increased activity (by definition, i.e. > 195 nmol/ min/ ml) was observed in 21.1 % of sample, no apparent difference between subject with and without manifest vascular disease was found. Males showed higher Lp PLA2 activity, than females (179.6 vs 146, resp., p < 0.0001), while no substantial increase with age was observed. Taking Lp PLA2 activity > 195 as dependent variable, following independent variables entered the multiple logistic regression: male gender [with odds ratio 4.26 (3.26- 5.58)], low HDL cholesterol (i.e. < 1.0 mmol/ l in males or < 1.2 mmol/ l in females) [3.49 (2.62- 4.64)], LDLcholesterol > 2.5 mmol/ l [6.95 (4.79- 10.07)] and lipid  lowering treatment [0.59 (0.44- 0.79)]. In subject without manifest vascular disease, 6.3 % of them showed co incidence of markedly increased Lp PLA2 activity with high conventional risk (SCORE > 10 %). Expanding this group by intermediate risk subjects (ie. with Lp PLA2 activity 152- 194 and/ or SCORE 5- 9.9 %) leads to increase of this prevalence to 28.9 % of primary prevention subjects. CONCLUSION: Increased Lp PLA2 activity is in Czech population highly prevalent and with exception of lipid parameters, generally independent from conventional cardiovascular risk. However, up to 29 % of subject in primary prevention amalgamate increased Lp PLA2 activity with high conventional cardiovascular risk.

The association between low 25-hydroxyvitamin D and increased aortic stiffness.

There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. We studied the association between vitamin D and arterial stiffness in a random sample of 560 subjects selected from general population. Arterial stiffness was measured as aortic pulse-wave velocity (PWV) using Sphygmocor device. Serum 25-hydroxyvitamin D (25(OH)D) was measured using commercial kits. We found a clear negative trend in aortic PWV among 25(OH)D quartiles. Subjects in the bottom 25(OH)D quartile (<20 ng ml(-1)) showed the highest aortic PWV (9.04 m s(-1)), compared with 2nd-4th quartile (8.07 m s(-1), 7.93 m s(-1) and 7.70 m s(-1), respectively; P for trend <0.0001). The association between 25(OH)D and aortic PWV remained significant after adjustment for age, gender and other potential confounders; subjects in the first 25(OH)D quartile had adjusted odds ratio 2.04 (1.26-3.30) for having aortic PWV ≥9 m s(-1) (top quartile) in multiple regression. In conclusion, we found a clear significant and independent negative association between 25(OH)D and aortic PWV. Subjects with lowest vitamin D status showed the highest arterial stiffness.

Relation of central and brachial blood pressure to left ventricular hypertrophy. The Czech Post-MONICA Study.

Central blood pressure (BP) has been shown to be a better predictor of target organ damage and cardiovascular events than brachial BP. Whether central BP is a better predictor of left ventricular hypertrophy (LVH) determined by electrocardiography (ECG) is not known. Radial applanation tonometry and ECG were performed in 728 subjects from the Czech Post-MONICA Study (a randomly selected 1% population sample). LVH was determined using the Sokolow-Lyon index and Cornell product; central pressure was derived from radial pulse. Of 657 subjects included in the analysis, 17 (9.4%) below 45 years and 43 (9%) over 45 years had LVH. In multiple linear regression analysis, the Sokolow-Lyon index in younger individuals was only associated with male sex and low BMI, with no association with BP found. In older individuals, LVH was associated with higher central and brachial BP. In separate binary logistic regression analyses adjusted for covariates, the odds ratio for central systolic pressure was higher than those for brachial systolic and pulse pressure in LVH prediction. Noninvasively determined central pressure in subjects over 45 years is more strongly related to ECG LVH than brachial pressure. This further supports a closer association of central pressure with target organ damage. Voltage criteria of LVH are not independently associated with central or brachial BP in younger individuals.

A novel oscillometric device for peripheral arterial disease screening in everyday practice. The Czech-post MONICA study.

AIM: Ankle brachial index (ABI) is a diagnostic tool for peripheral arterial disease (PAD) and a cardiovascular risk stratification tool. Despite this evidence and guidelines recommending its use in everyday practice, ABI is not widely used. Automatic ABI measurement may lower the barrier to incorporate ABI measurement into everyday practice. The aim of this study was to validate a novel automatic oscillometric ABI device (BOSO ABI) against a gold standard-Doppler device in an epidemiological setting. METHODS: In 839 patients from the Czech post-MONICA study (a randomly selected representative population sample aged over 25 years), mean age 54.3±13.8 years (47% of men), ABI measurement was performed using the BOSO ABI device and a handheld Doppler device in a random fashion. The two techniques were carried out by different investigators each blinded to the findings of the other. Analyses were conducted as proposed by Bland and Altman. RESULTS: The mean ABI difference between the two methods was 0.1±0.11, with 95% limits of agreement ranging from -0.11 to 0.30. The difference between Doppler and oscillometric ABI increased significantly with increasing mean ABI (r=0.29; P<0.001). When considering Doppler the gold standard, automated oscillometric measurement had a 76.9% sensitivity, 97.9% specificity, and 37% positive and 99.6% negative predictive values in diagnosing ABI <0.9. CONCLUSION: The BOSO ABI device cannot be used interchangeably for standard Doppler ABI measurement in diagnosing PAD. However, its high negative predictive value allows using it as a screening tool for PAD.

An inverse association between serum leptin concentration and reported alcohol intake in patients with manifest vascular disease.

BACKGROUND/OBJECTIVES: It has been reported that alcohol stimulates appetite. We aimed to establish the association between leptin, as a major food intake regulating factor, and alcohol intake in patients with chronic manifest coronary artery or cerebrovascular disease. SUBJECTS/METHODS: A cross-sectional study of 820 subjects after acute coronary syndrome, coronary revascularization or after first ischemic stroke (the Czech part of EUROASPIRE III surveys). Leptin concentrations were evaluated among predefined categories of reported weekly alcohol intake: abstainers, light drinkers (up to 2 drinks weekly, 1-44 g of pure alcohol), mild regular drinkers (3-14 drinks weekly, 45-308 g) and moderate or heavy drinkers (more than 15 drinks, ≥ 309 g of alcohol). RESULTS: Leptin showed a clear negative trend among the alcohol intake categories. Mild regular drinkers showed significantly lower leptin levels (9.3(8.2) ng/ml) compared with abstainers (18.7(18.7) ng/ml, P<0.0001) and light occasional drinkers (14.2(17.8) ng/ml, P=0.00064). The negative association between leptin and alcohol intake as a dependent variable remained significant even after adjustment for potential confounders in multiple linear regression analysis (P=0.00032). CONCLUSIONS: Drinking of small amounts of alcohol was, in our setting, associated with decreased serum leptin concentration, with a possible benefit in terms of cardiovascular risk.

Risk factors for residual thrombotic occlusion after proximal deep vein thrombosis of the legs.

AIM: Residual thrombotic occlusion (RTO) after deep vein thrombosis (DVT) is considered as a risk factor of recurrent venous thromboembolism (VTE). We searched for risk factors associated with RTO after proximal DVT at the lower extremities. METHODS: Using compression ultrasound, we evaluated the presence of RTO at 6 months after DVT (RTO defined as a residual thrombus occupying, at maximum compressibility, >/=20% of the vein lumen before compression). RESULTS: We examined 126 Czech patients: mean age 57.5 years; 50.0% women, 68.3% femoral location of DVT (otherwise popliteal), RTO found in 45.2%. While accounting for covariates, in the whole population, RTO was significantly associated with following factors: (OR; 95% confidence limit; p value): male sex (2.01; 1.27-3.19; P=0.003), femoral location (2.76; 1.59-4.78; P=0.0003). In women, but not in men, an association was demonstrated for: concurrent pulmonary embolism (PE) (18.51; 1.85-185.7; P=0.0131), diabetes mellitus (4.62; 1.38-15.51; P=0.0133) and statin use (0.11; 0.02-0.62; P=0.0125). In contrast, in men RTO was associated with an unprovoked DVT (2.6; 1.26-5.34; P=0.0094). CONCLUSION: In the whole study population, male sex and femoral location of DVT were positively associated with RTO. In women, concurrent PE and diabetes mellitus were risk factors for RTO, while the use of statins was a protective factor. There was a positive association between RTO and unprovoked DVT in men. These findings deserve further evaluation in a larger study.

The interaction of endothelial nitric oxide synthase polymorphism and current smoking in terms of increased arterial stiffness.

Nitric oxide belongs to the most important factors influencing structural and functional properties of vessel wall. Both genetic and environmental factors may influence its metabolism. The aim of this study was to explore whether two common polymorphisms of endothelial nitric synthase (eNOS) may, jointly with smoking, influence the stiffness of large arteries, quantified as pulse wave velocity (PWV). One hundred ninety four subjects free of manifest atherosclerotic disease or chronic pharmacotherapy were selected from population-based postMONICA study. PWV´s were measured using Sphygmocor® device between carotic and femoral arteries (aortic PWV) and between femoral and tibialis-posterior arteries (peripheral PWV). Two common polymorphisms, T786C and G894T, were assessed. Among current smokers, homo- or heterozygous carriers of T786C mutation showed significantly higher peripheral PWV than normal genotype carriers (14.0 vs 10.7 m/s, p<0.002); the same was true for the carriers of G894T mutation (13.9 vs 11.0 m/s, p<0.015). No differences were found in non-smokers, and neither of the eNOS polymorphisms influenced aortic PWV in our setting. In conclusion, genetically determined disorder of nitric oxide metabolism was associated with increased stiffness of peripheral, muscular-type arteries in generally healthy, untreated subjects, but only in the interaction with current smoking.

Laboratory evaluation of antiphospholipid antibodies in patients with venous thromboembolism.

The objective of our study was to evaluate the significance of extended antiphospholipid profile in patients with venous thromboembolism without any systemic autoimmune disease. In 140 patients (age 18-69 years; 47.1% men) with venous thromboembolism and 136 control participants we tested anticardiolipin antibodies, anti-beta 2 glycoprotein I (anti-beta2-GPI) and also non-criteria antiphospholipid antibodies: antiphosphatidic acid, antiphosphatidylethanolamine, antiphosphatidylglycerol, antiphosphatidylinositol, antiphosphatidylserine. Commercial and in-house enzyme-linked immunosorbent assays were used. The antibodies with significantly higher prevalence in patients (compared to controls) were: immunoglobulin (Ig) M-anticardiolipin antibodies (12.9%; P = 0.035), IgG-anti-beta2-GPI (16.4%; P = 0.0032), IgM-antiphosphatidylethanolamine (14.3%; P = 0.014). In most cases, these three antibodies did not overlap. In conclusion, of non-criteria antiphospholipid antibodies, only antiphosphatidylethanolamine were significantly more prevalent in patients with venous thromboembolism, with only minor overlapping with the criteria antiphospholipid antibodies. Our results suggest the possible utility of searching for antiphosphatidylethanolamine in the clinical suspicion of antiphospholipid syndrome and the absence of criteria antiphospholipid antibodies.

[Ivabradine in patients with stable ischemic heart disease and left ventricular systolic dysfunction: the results of the BEAUTIFUL study]. / Ivabradin u nemocných se stabilní ischemickou chorobou srdecní a systolickou dysfunkcí levé srdecní komory: výsledky studie BEAUTIFUL.

Ivabradine reduces heart rate by inhibiting the If channels mediated current, while sinus rhythm is sustained. The aim of the BEAUTIFUL study was to assess whether the administration of ivabradine to patients with stable ischemic heart disease and ejection fraction < or = 40% will result in reduction of cardiovascular morbidity and mortality. This was a double blind randomized study including 10,917 patients. Half of the patients were administered placebo and half were treated with ivabradine additional to the treatment normally used in the secondary prevention ofischemic heart disease; the starting dose was 5 mg twice a day and could be increased to 7.5 mg twice a day. The combined primary endpoint was cardiovascular-event related death, hospitalization for acute myocardial infarction and hospitalization for heart failure. The follow up was 19 months. Ivabradine decreased heart rate by 6 beats/min. The majority of patients took beta-blockers (87%) and combination with ivabradine was well tolerated. Ivabradine did not significantly affect the combined primary endpoint. Significant reduction by 36% (p = 0.001) in myocardial infarction and by 30% (p = 0.016) in coronary revascularization was observed in the pre-defined subgroup of patients with heart rate > or = 70/min. Adverse events rate was the same in the active and the control groups. It is possible to conclude that ivabradine did not improve cardiovascular prognosis in all patients with stable ischemic heart disease and decreased ejection fraction but was beneficial as an additional add-on treatment to the current medication, including beta-blockers, in patients whose heart rate was > or = 70/min.

Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on arterial stiffness.

Angiotensin II and nitric oxide belong to important factors in the functional and structural changes of vessel wall, leading to its increased stiffness. We investigated, whether common mutations of angiotensin II type 1 receptor (AGTR(1)) and endothelial nitric oxide synthase (eNOS) are associated with increased arterial stiffness. Two polymorphisms, A(1166)C of AGTR(1) and T(786)C of Enos, were estimated in a random, general population-based sample of 250 subjects. Arterial stiffness was measured using Sphygmocor as aortic (carotid-femoral) and peripheral (femoral-tibial) pulse wave velocities (PWV). Carriers of 3-4 mutant alleles from both polymorphisms, that is, homozygous for both mutations or homozygous for one and heterozygous for the second one, showed significantly higher peripheral PWV (17.92+/-2.40) than those with none or only 1-2 mutant alleles (12.37+/-0.51; P<0.003). Carriers of 3-4 mutant alleles had three times higher risk of having increased peripheral PWV (>or= 13.63 m s(-1), that is, in the top quartile) and this association remained significant after adjustment for potential confounders. No association was found between estimated genotypes and aortic PWV. In conclusion, combination of A(1166)C of AGTR(1) and T(786)C of eNOS mutations increased stiffness of muscular-type arteries.

Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population.

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor device. Aortic PWV (APWV) positively correlated with tHcy (r = 0.28, P<0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P = 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B12, renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy > or = 15 micromol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.

[Clinical importance of aspirin resistance]. / Klinický význam aspirinové rezistence.

The antiplatelet effect of aspirin is mostly explained by the irreversible cyclooxygenase-1 inhibition resulting in the suppression of thromboxane A2 synthesis. The benefit of aspirin was proved in various cardiovascular diseases. However, the inter- and intraindividual variability of its antiplatelet effect is well known. Aspirin resistance can be understood from the clinical point of view--as a failure of the protective effect of aspirin from thrombotic complication or can be defined from the laboratory aspect--as an inability to cause in vitro detectable platelet function inhibition. The cause of this phenomenon has not been completely explained yet and more mechanisms have been proposed, incomplete suppression of thromboxane A2 generation being one of them. Laboratory diagnostics of aspirin resistance is based on the demonstration of the insufficient inhibition of platelet aggregation or the incomplete suppression of thromboxane A2 synthesis (assay for its metabolite, 11-dehydrothromboxane B2 in urine). The results of some trials raise the possibility that aspirin resistance could be a new independent predictor of cardiovascular events.