Wall shear stress in the development of in-stent restenosis revisited. A critical review of clinical data on shear stress after intracoronary stent implantation.

The average wall shear stress (WSS) is in 1 Pa range in coronary arteries, while the stretching effect of an implanted coronary stent can generate up to 3 × 105 times higher circumferential stress in the vessel wall. It is widely accepted that WSS plays a critical role in the development of restenosis after coronary stent implantation, but relevant clinical endpoint studies are lack-ing. Fluid dynamics modeling suggests an association between WSS and intimal hyperplasia, however, such an association is not established when the compensating healing process becomes an overshoot phenomenon. This review summarizes available clinical results and concepts of potential clinical importance.

Plasma homocysteine levels are related to medium-term venous graft degeneration in coronary artery bypass graft patients.

OBJECTIVE: Saphenous venous grafts (SVGs) are established choices for coronary artery bypass grafting (CABG); however, their lumen patency is limited. Our goal was to investigate the risk factors of SVG degeneration. METHODS: Seventy-five patients (mean age, 57.5±10.4 years) with 133 SVG conduits who had cardiac catheterization ≥1 year after CABG were selected; follow-up period was 67.6±36.8 months. Patients were divided into 3 groups according to angiographic status at follow up [intact: <20% (n=23); narrowed: 20-99% (n=24); and occluded (n=28)]. Baseline clinical conditions were evaluated in relation to follow-up angiography. As onset date of chronic total occlusions is usually uncertain, they arise typically from thrombotic lesions; thus, their value in evaluation is limited. RESULTS: There were no significant differences between the 3 groups in clinical parameters. Linear correlation analysis found significant (p<0.01) positive connection of SVG disease (luminal diameter reduction 20-99%) with C-reactive protein (CRP) and homocysteine (Hcy), as well as between CRP and Hcy. Multiple regression analysis showed plasma Hcy level to be significantly related to graft diameter reduction normalized to time elapsed until angiography in narrowed grafts: 1 µmol/L increase of Hcy was associated with 0.053%/month decrease in lumen diameter (p<0.01; R2=0.428); extrapolating: +10 µmol/L higher Hcy level during 5 years is associated with 32.1% lumen reduction. CONCLUSION: Medium- to long-term SVG degeneration is related to elevated plasma total Hcy in patients with sub-occlusive graft stenosis, while in cases with intact SVGs, the beneficial local flow conditions may protect the grafts from degeneration.

Factor XIII B subunit polymorphisms and the risk of coronary artery disease.

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

Interaction between homocysteine and lipoprotein(a) increases the prevalence of coronary artery disease/myocardial infarction in women: a case-control study.

INTRODUCTION: Our aim was to investigate the association of elevated homocysteine (Hcy) and lipoprotein(a) Lp(a) with the prevalence of coronary artery disease (CAD) and myocardial infarction (MI) and to investigate their interaction in both genders. MATERIALS AND METHODS: 955 (male/female: 578/377) consecutive patients admitted for coronary angiography were enrolled in the study. Lp(a), Hcy, vitamin B12, folic acid, MTHFR C677T polymorphism and traditional risk factors were determined. RESULTS: 619 patients had significant (≥50%) stenosis (CAD+) and 341 had MI (MI+). CAD-MI- cases (n=302) were considered as controls. Adjusted Hcy levels were significantly elevated only in the female CAD+MI+group that was related to decreased vitamin B12 levels. Lp(a) was elevated in the CAD+MI+group of both genders. Folic acid levels and MTHFR T677 allele frequency did not show significant difference. Moderate hyperhomocysteinemia (Hcy >15µmol/L) or elevated Lp(a) (>300mg/L) increased the risk of CAD (OR 2.27, CI 1.36-3.80 and OR 1.64, CI 1.03-2.61, respectively) and MI (OR 2.52, CI 1.36-4.67 and OR 1.89, CI 1.06-3.38, respectively) only in women. Only simultaneous but not isolated elevation of Hcy and Lp(a) conferred a significant, 3.6-fold risk of CAD in females and even higher (11-fold) risk in young females, which suggested an interactive effect. CONCLUSIONS: Moderate hyperhomocysteinemia or elevated Lp(a) level associated with a risk of CAD and MI only in women. While isolated elevation of one of the two parameters represented a mild risk of CAD, their combined elevation highly increased the risk in females. No such effect was observed in males.

Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease.

INTRODUCTION: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of coronary artery disease (CAD) has been extensively studied. In this study we investigated how FXIII-A Val34Leu genotypes influence plasma factor XIII levels in patients with coronary sclerosis (CS) and myocardial infarction (MI) and how fibrinogen level modulates this effect. PATIENTS AND METHODS: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant CS and the history of MI. The frequency of FXIII-A Val34Leu polymorphism, fibrinogen, FXIII activity and antigen levels were determined. RESULTS AND CONCLUSIONS: CS or MI decreased FXIII levels in patients homozygous for FXIII-A Leu34 allele, but not in heterozygous or wild type patients. In the subgroup of patients with CS, but without the history of MI no significant effect was detected, which suggests that MI has a more prominent role. The specific activity of plasma FXIII was independent of FXIII-A Val34Leu genotype. FXIII and fibrinogen levels significantly correlated in CS+ and MI+ patients. In MI+ patients of Leu/Val or Leu/Leu genotypes and with fibrinogen levels in the lowest quartile, FXIII levels were lower than in the same patient groups, but with higher fibrinogen level. The low-scale continuous activation of blood coagulation in CAD patients could lead to parallel FXIII and fibrinogen consumption. As the same amount of thrombin activates more Leu34 FXIII than Val34 FXIII, increased FXIII consumption might be responsible for the decreased FXIII levels in Leu34 homozygous CAD patients.

Holistic polar map for integrated evaluation of cardiac imaging results.

Polar map display (PM) is a comprehensive interpretation of the left ventricle. This is a non-rigid registration of the left ventricle originally for the visual and quantitative analysis of tomographic myocardial perfusion scintigrams. In this scheme the maximal-count circumferential profiles of well-defined short- and long-axis planes are plotted to a map showing the distribution of the perfusion tracer onto a two-dimensional polar representation. The usual coronary artery distribution is often indicated on the PMs of SPECT studies by referring to the regions of the three main coronary branches, nevertheless, the individual variations may differ extensively. We set out to develop an Access (Microsoft)-based computer program that permits an integrated evaluation of the imaging results (coronary angiography, echocardiography and SPECT) on patients with coronary artery disease. This semi-quantitative registration of the coronary tree to a PM focused on the relation between the supplying coronary branches and the myocardial regions of the 16-segment left ventricular evaluating model. All the recorded anatomical and functional data were related to these 16 left ventricular segments, which allowed the direct comparison and holistic synthesis of the results. Two projections were taken into consideration for generation of the coronary PM: from the right anterior oblique projections, the left anterior descendent (LAD)/right coronary artery (RCA) border was assessed through the comparison of the left and right coronary angiograms. The terminations of the visually detected end-arteries showed the separation of the myocardial beds supplied by the two branches. The border of the myocardial beds on the polar map was determined on the "vertical axis" of the local coordinate system. The RCA/ left circumflex (LCx) separation can be determined from the left anterior oblique view. In this projection, the left ventricular septal edge was delineated by the LAD, while the LCx indicated the lateral epicardial surface. The individual coronary artery circulation was typified from among 12 variations in the Holistic Coronary Care program. With this determination of the individual coronary circulation, the lesion-associated segments are generated automatically by the software. The lesion-associated regions are defined as the myocardial bed of a diseased artery distal to the lesion. The PMs generated from the coronary angiographic results were compared with those of 99Tc-labelled MIBI single photon emission computed tomography (SPECT) in order to test the accuracy of the localizing method. The overlap between the segments associated with the coronary lesion and the stress perfusion defects (<80% relative MIBI activity during stress tests) was analyzed in 10 patients with (sub)total coronary occlusion after myocardial infarction. The distributions of the segments with stress perfusion defects on MIBI SPECT gave positive and negative predictive values of coronary occlusion of 0.94 and 0.8, respectively. According to the 16-segment wall motion analysis by echocardiography, the positive and negative predictive values of coronary occlusion for wall motion abnormality were 0.82 and 0.76, respectively. While the distal part of the subtended region usually demonstrated a higher degree perfusion abnormality than the proximal part, the high positive predictive value proved that, during the stress condition, the perfusion defect could be detected in practically all the subtended regions. The low negative predictive value of the coronary lesion for the wall motion abnormality was associated with the remodeling of the entire left ventricle.

Elevated factor XIII level and the risk of myocardial infarction in women.

Factor XIII (FXIII) activity and antigen levels were determined in 955 patients investigated by coronary angiography. Patients were sub-grouped according to the presence or absence of coronary sclerosis (CS+, CS-) and a positive history of myocardial infarction (MI+, MI-). In females, but not in males, adjusted FXIII activity and antigen levels were significantly elevated in the CS+MI+ group compared to in the CS+MI- group. FXIII levels in the upper tertile were associated with significantly increased risk of MI in females, but not in males.

Modulation of the risk of coronary sclerosis/myocardial infarction by the interaction between factor XIII subunit A Val34Leu polymorphism and fibrinogen concentration in the high risk Hungarian population.

INTRODUCTION: The results on the association of factor XIII (FXIII) A subunit (FXIII-A) Val34Leu polymorphism with the risk of myocardial infarction (MI) are rather inconclusive. The original paper and confirmatory reports demonstrated a protective effect of the mutation, but results demonstrating the lack of protection have also been published. Gene-gene and gene-environmental interactions have been proposed to be responsible for the opposing results. As the rate of change in fibrin clot permeability with increasing fibrinogen concentrations decreased stepwise with increasing number of Leu34 alleles it was proposed that the protection by Val34Leu polymorphism become effective only at higher fibrinogen concentrations. However, this hypothesis has not been tested on patients with coronary artery disease. PATIENTS AND METHODS: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant coronary sclerosis (CS) and according to positive or negative history of MI. The frequency of FXIII-A Val34Leu polymorphism, and a number of risk factors, including fibrinogen were determined in the patients. FXIII-A Val34Leu polymorphism was also investigated in a population control group of 1146 subjects. RESULTS: The presence of FXIII-A Leu34 allele or homozygous Leu34 genotype did not change the risk of CS or MI in the general Hungarian population. However, when patients with fibrinogen level in the upper quartile were separately investigated, the Leu34 allele provided a statistically significant protection against MI. CONCLUSIONS: Fibrinogen concentration modulates the effect of Leu34 allele on the risk of MI; its protective effect emerges at increasing fibrinogen concentration.

[Increase of homocysteine in cardiovascular diseases in Hungary]. / Magasabb homociszteinszint cardiovascularis betegségekben Magyarországon.

UNLABELLED: There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases. AIM OF THE STUDY: Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences. PATIENTS AND METHODS: From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis. RESULTS: The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women. CONCLUSIONS: It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.