ABSTRACT
Background: the C1019T polymorphism of the connexin-37 [GJA4] gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction [MI] in patients with premature coronary artery disease [CAD]
Methods: our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI [n = 461] and without it [n = 539]. The polymorphism variants were determined via the PCR-RFLP, and then genotyping was conducted through the high-resolution melting method. From a total of 1000 patients, 554 patients, who had been previously followed-up with a median follow-up time of 45.74 months vis-à-vis long-term major adverse cardiac events, were enrolled in this retrospective cohort phase
Results: the frequencies of the wild, heterozygous, and mutant genotypes of the C1019T polymorphism were 54.0%, 40.6%, and 5.4% in the MI group and 49.2%, 43.2%, and 7.6% in the non-MI group [p value = 0.187]. After adjustment for the baseline covariates, no difference was found between the MI and non-MI groups apropos the frequency of the heterozygous genotype [p value = 0.625] and the mutant genotype [p value = 0.452]. Regarding the level of human connexin-37, the serum level of this marker was not different between the MI and non-MI groups
Conclusion: the C1019T polymorphism of the GJA4 gene may not be useful for predicting the occurrence of MI in patients with premature CAD. The presence of this polymorphism in such patients may also have a low value for predicting long-term CAD complications
ABSTRACT
Background: hepatic lipase [HL] plays a crucial role in lipid metabolism, but there is debate about whether HL acts in a more pro- or more anti-atherogenic fashion. We aimed to examine the relationship between the -514 C/T polymorphism within the HL gene [LIPC] and the risk of angiographically determined premature coronary artery disease [CAD]
Methods: four hundred seventy-one patients with newly diagnosed angiographically documented [>/= 50% luminal stenosis of any coronary vessel] premature CAD were compared to 503 controls [subjects with no luminal stenosis in coronary arteries]. A real-time polymerase chain reaction and high-resolution melting analysis was used to distinguish between the genotypes
Results: there was no significant difference in the distribution of -514 C/T genotypes between the 2 groups in the whole population or in the men, but the examined polymorphism was found to be associated with the presence of CAD in the women [p value = 0.029]. After the application of a multiple logistic regression model, the minor T allele of the LIPC gene was not found to be independently associated with the presence of CAD either in the total population [adjusted OR = 0.97, 95% CI = 0.75-1.25; p value = 0.807] or in the women [adjusted OR = 0.91, 95% CI = 0.59-1.40; p value = 0.650] and in the men [adjusted OR = 1.15, 95% CI = 0.81-1.64; p value = 0.437] separately
Conclusion: our findings suggest that there is no relationship between the LIPC -514 C/T and the risk of premature CAD or its severity in patients undergoing coronary angiography
ABSTRACT
Background: Investigators frequently encounter continuous outcomes with plenty of values clumped at zero called semi-continuous outcomes. The Gensini score, one of the most widely used scoring systems for expressing coronary angiographic results, is of this type. The aim of this study was to apply two statistical approaches based on the categorization and original scale of the Gensini score to simultaneously assess the association between covariates and the presence and severity of coronary artery disease [CAD]
Methods: We considered the data on 1594 individuals admitted to Tehran Heart Center with CAD symptoms from July 2004 to February 2008. The participants' baseline demographic and clinical characteristics were collected, and their coronary angiographic results were expressed through the Gensini score. The generalized ordinal threshold and two-part models were applied for the statistical analyses
Results: Totally, 320 [20.1%] individuals had a Gensini score of zero. The results of neither the two-part model nor the generalized ordinal threshold model showed a significant association between Factor V Leiden and the occurrence of CAD. However, based on the two-part model, Factor V Leiden was associated with the severity of CAD, such that the Gensini score increased by moving from a wild genotype to a heterozygote [beta = 0.44; 95% CI: 0.20-0.69 in logarithm scale] or a homozygote mutant [beta = 0.70; 95% CI: 0.28- 1.12 in logarithm scale]. The proportional odds assumption was not met in our data [= 54.26; p value < 0.001]; however, a trend toward severe CAD was also observed at each category of the Gensini score using the generalized ordinal threshold model
Conclusion: We conclude that besides loss of information by sorting a semi-continuous outcome, violation from the proportional odds assumption complicates the final decision, especially for clinicians. Therefore, more straightforward models such as the two-part model should receive more attention while analyzing such outcomes
ABSTRACT
N-terminal pro beta-type natriuretic peptide [NT-proBNP] is a valuable marker for monitoring the response to treatment in patients with heart failure. Based on the clinically observed improvement of heart failure symptoms early after cardiac resynchronization therapy [CRT], we sought to investigate whether CRT induce any significant reduction in the plasma level of NT-proBNP in three days after implantation and whether it is correlated with patients' response at six months. In this prospective study, 21 consecutive patients with severe heart failure [New York Heart Association class 3.19 +/- 0.40] who underwent CRT were enrolled. Being alive, no hospitalization due to decompensated heart failure, and improvement of at least one NYHA functional class at six months were classified as clinical responsiveness. The plasma level of NTproBNP was measured before, three days, and six months after CRT. Clinical evaluation, echocardiographic study, and six-minute walking test were performed before and six months after the procedure. At six months' follow-up, 16 [76.2%] patients were responders. The plasma level of NT-proBNP at three days after CRT increased almost equally in both responder and non-responder groups of patients [Delta NT-proBNP was 40.94 +/- 135.74 vs. 54.80 +/- 88.98]; however, at six months' follow-up, the NT-proBNP changes statistically differed across the two groups of patients [P=0.005]. According to our findings, NT-proBNP percent deviation from baseline to three days after CRT appears to be not correlated with the patients' clinical response after six months, which was incongruent to the patients' clinical improvement after CRT
Subject(s)
Humans , Male , Female , Peptide Fragments , Heart Failure , Cardiac Resynchronization Therapy , Prospective Studies , Pilot ProjectsABSTRACT
Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter-and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time [PT] and the activated partial thromboplastin time [aPTT] are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio [INR] was introduced to normalize-all PT reagents to a World Health Organization [WHO] reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists [VKAs] [i.e., at least 6 weeks of VKA therapy], and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation, and congenital factor deficiencies. In contrast to marked progress in the standardization of PT reagents for INR reporting, no standardization system has been globally adopted for standardization of PTT reagents. Recently College of American Pathologists recommend that individual laboratories establish their own therapeutic range by using aPTT values calibrated against accepted therapeutic unfractionated heparin [UFH] levels calibrated against accepted therapeutic UFH levels performing anti-Xa test [which is the most accurate assay for monitoring UFH therapy]. Herein, we review recent data on the monitoring of conventional anticoagulant agents. Marked interlaboratory variability still exists for PT, INR, and PTT tests. Further research should be focused on improving the standardization and calibration of these assays