The significance of E/E′ to detect coronary artery disease during dobutamine stress echocardiography

AimTo determine how the left ventricular diastolic filling pressure determined by E/E′ during dobutamine stress echocardiographic (DSE) by tissue Doppler Imaging (TDI) is affected by the presence and the severity of coronary artery disease (CAD) among patients with stable angina pectoris and also its relation to inducible ischemia.Patients and methodsThis study comprises 60 patients with suspected angina pectoris. All subjects were examined with DSE and TDI to assess resting mean E/E′ at peak stress, E/E′ change and E/E′ index. Coronary angiography was performed within 1 month.ResultsCoronary angiography revealed CAD in 38 patients (CAD group) while the remaining 22 patients formed the non-CAD group. There is a significant decrease of peak E′, S′ and increase peak E/E′ in CAD group during stress compared to non-CAD group (P < 0.01, P < 0.05 and P < 0.001, respectively). Thirty-two patients with inducible ischemia during stress had higher peak E/E′, E/E′ index compared to 28 patients with non-inducible ischemia. Receiver operating curve analysis showed an optimal cut-off value of peak E/E′, E/E′ change, E/E′ index (>4.11, >0.9 and >0.8, respectively) for the presence of CAD (area under curve 0.91, 0.93 and 0.88, respectively P < 0.001 for all). Sensitivities for detection of CAD were 94.7%, 84.2% and 89.5% and specificity was 90.9%, 72.7% and 74.7%, respectively. Peak E/E′, E/E′ index increased proportionally with the number of stenotic vessels (r = 0.89 and 0.76, respectively, P < 0.001).ConclusionDuring DSE the changes of mean E/E′ ratio are associated with inducible ischemia, the presence of CAD and the extent of CAD. So, E/E′ can be used as objective evidence during DSE.     

Coronary artery disease screening in type II diabetic patients: Prognostic value of rest and stress echocardiography

Aim:Presence of inducible ischemia in type II diabetic patients is associated with an adverse outcome, but less is known about prognostic value of resting wall motion abnormalities (WMA).Materials and methods: From October 2006 to May 2008, 278 patients underwent to CAD screening, according to ADA criteria, by dobutamine stress echocardiography (DSE). Between July and September 2009, all patients were contacted to verify the occurrence of new cardiac events.ResultsResting-WMA were present in 63 patients; 88 subjects showed inducible ischemia. During the follow-up, we observed 24 new cardiac events; patients with a good outcome showed less frequently resting WMA (19 vs 50%). Inducible ischemia (71% vs 28%; p < 0.001) and a more extensive area of inducible ischemia, expressed by a higher value of peak WMSI (1.63 ± 0.45 vs 1.17 ± 0.31; p < 0.0001), were more frequent in patients with adverse outcome. A Cox regression analysis showed that only a higher peak WMSI (HR 6.645, 95% CI 2.782–15.874, p < 0.0001) was associated with a bad outcome. Event-free survival was lower in presence of rest WMA (79% vs 94%, p < 0.0001) and a higher peak WMSI (66% vs 95%, p < 0.0001).ConclusionsIn diabetic patients presence of an extensive inducible ischemia was independently associated with a worst outcome; resting WMA were associated with reduced event-free survival.     

Aortic stiffness is increased in patients with premature coronary artery disease: A tissue Doppler imaging study

BackgroundAtherosclerosis and arterial stiffening may coexist and the correlation of these parameters in patients with premature coronary artery disease (CAD) has not been well elucidated. Tissue Doppler imaging of the ascending aorta may be used in the assessment of elastic properties of the great arteries.ObjectiveTo investigate the correlation between aortic stiffness and premature CAD using parameters derived from two-dimensional and tissue Doppler imaging (TDI) echocardiography of the ascending aorta.MethodsFifty consecutive subjects younger than 40 years old who were hospitalized with diagnosis of acute coronary syndrome and had undergone coronary angiography were recruited. The control group included 70 age–sex matched individuals without a diagnosis of CAD. Aortic stiffness index (SI), aortic distensibility (D), and pressure-strain elastic modulus (E_p) were calculated from the aortic diameters measured by two-dimensional M-mode echocardiography and blood pressure obtained by sphygmomanometry. Aortic systolic velocity (S_Ao), and early (E_Ao) and late (A_Ao) diastolic velocities were determined by pulse-wave TDI from the anterior wall of ascending aorta 3 cm above the aortic cusps in parasternal long-axis view.ResultsStiffness index was higher [median 5.40, interquartile range (IQR) 5.98 vs. median 4.14 IQR 2.43; p = 0.03] and distensibility was lower (median 2.86 × 10⁻⁶ cm²/dyn, IQR 2.51 × 10⁻⁶ cm²/dyn vs. median 3.46 × 10⁻⁶ cm²/dyn, IQR 2.38 × 10⁻⁶ cm²/dyn; p = 0.04) in patients with CAD compared to the control group. E_Ao was significantly lower in the CAD group (7.2 ± 1.8 cm/s vs. 9.2 ± 2.4 cm/s, p < 0.01). The difference in E_Ao remained significant when CAD patients with a left ventricular ejection fraction >55% was compared to the control group. S_Ao and A_Ao velocities of ascending aorta were similar in control and CAD groups. There was a significant correlation between E_Ao velocity and aortic stiffness index (r = −0.28, p = 0.01), distensibility (r = 0.19, p = 0.04) and elastic modulus (r = −0.24, p = 0.01). In multivariate regression analysis, decreased levels of high-density lipoprotein cholesterol [odds ratio (OR): 1.12 95% CI 1.06–1.19; p = 0.01] and E_Ao (OR: 1.41 95% CI 1.12–1.79; p = 0.01) measurements remained as the variables independently correlated with premature CAD in the study group.ConclusionArterial stiffness is increased in patients with premature CAD. E_Ao of the anterior wall of ascending aorta measured with pulse-wave TDI echocardiography is correlated with arterial stiffening and is decreased in patients with premature CAD.     

Presence of coronary artery disease in diabetic and non diabetic South Asian immigrants

IntroductionSouth Asian Immigrants (SAIs) are the second fastest growing Asian immigrant population in the US, and at a higher risk of type 2 diabetes (diabetes) and coronary artery disease (CAD) than the general US population. Objectives: We sought to determine in SAIs the; 1) the prevalence of CAD risk factors in diabetics and non-diabetics; and b) the high possibility of CAD in diabetic SAIs. We also assessed the prevalence of sub-clinical CAD in both diabetics and non-diabetics SAIs using common carotid artery Intima-media thickness (CIMT) as a surrogate marker for atherosclerosis.MethodsIn a cross-sectional study design, 213 first generation SAIs were recruited and based on the history, and fasting glucose levels were divided into two subgroups; 35 diabetics and 178 non-diabetics. 12-hour fasting blood samples were collected for glucose and total cholesterol levels. Exercise Tolerance Test (ETT) was performed to determine the possibility of CAD.ResultsBoth diabetics and non-diabetics SAIs in general, share a significant burden of CAD risk factors. The prevalence of hypertension (p = 0.003), total cholesterol ≥ 200 mg/dl (p < 0.0001) and family history of diabetes (p < 0.0001) was significantly was significantly higher in diabetics compared to non-diabetics. Of the 22/29 diabetic participants without known history of CAD, 45% had positive ETT (p < 0.001). Similarly, 63.1% of diabetics and 51.8 % of non-diabetics were positive for sub-clinical CAD using CIMT as a marker.ConclusionThe susceptibility to diabetes amongst SAIs promotes an adverse CAD risk, as evident by this small study. Further research, including larger longitudinal prospective studies, is required to validate the current small study findings with investigation of the temporal association.     

Tissue Doppler systolic annular velocity and myocardial performance index as predictors of right ventricular affection and culprit lesion location in acute inferior myocardial infarction

AimThis study aims at using peak lateral tricuspid annular systolic velocity (S_T) and right ventricular myocardial performance index (RV-MPI) as predictors of RV infarction (RVI) and subsequently localizing the culprit lesion in the proximal right coronary (RCA) rather than other locations [the distal RCA or dominant left circumflex (LCX) artery].Patients30 patients suffering from acute inferior infarction, were subjected to early conventional and pulsed wave tissue Doppler echocardiographic examinations, measuring (S_T) and calculating RV-MPI. Half of the patients had the culprit lesion proximal to the RV branch of the RCA and the other half had non-proximal RCA occlusion.ResultsS_T values were significantly reduced in patients with RVI. Cutoff value of S_T was found to be 11.9 cm/s with a sensitivity 80.0%, specificity 93.3%, positive predictive value 92.3% and negative predictive value 82.4% in the identification of proximal RCA lesion as the culprit lesion.The calculated RV-MPI was significantly different; its mean value was 0.666 ± 0.118 in the proximal RCA vs. 0.524 ± 0.133 in the non-proximal RCA patients. RV-MPI cutoff value proved to be 0.50 with sensitivity 80%, specificity 66.7%, negative predictive value 76.9% and positive predictive value 70.6%.ConclusionRVI caused by a proximal RCA lesion could be predicted using TDI to assess S_T and RV-MPI from the tricuspid annulus. Patients with S_T < 11.9 cm/s and RV-MPI ⩾ 0.5 indicated most probably occlusion of the proximal RCA.     

Prediction of cardiovascular events in pre-dialysis chronic kidney disease patients with normal SPECT myocardial perfusion imaging

PurposePatients with normal stress myocardial perfusion imaging (MPI) results generally have an excellent prognosis with <1% cardiovascular events/year. Chronic kidney disease (CKD) is an established risk factor for cardiovascular events. However, the estimated glomerular filtration rate (eGFR) varies considerably among patients with CKD. We evaluated the prognostic value of eGFR for patients with CKD who did not undergo hemodialysis and had no evidence of coronary artery disease (CAD).Methods and subjectsPatients with CKD (n = 108; 58 males; mean age: 74 years) with no CAD [no previous CAD and normal stress MPI results; summed stress score (SSS) <4] and with no history of hemodialysis were followed-up (mean duration: 24 months). CKD was defined by eGFR of <60 ml/min/1.73 m² and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction, and unstable angina.ResultsCardiovascular events were observed in 8 patients with CKD (7%). The following were determined as significant predictors of these events: age (hazard ratio = 1.14; p = 0.019), hemoglobin levels (hazard ratio = 0.69; p = 0.021), eGFR (hazard ratio = 0.94; p = 0.008), SSS (hazard ratio = 2.31; p = 0.012), and summed difference score (hazard ratio = 2.33; p = 0.014).ConclusionsPatients with CKD and with no previous CAD and normal stress MPI results (SSS < 4) may not exhibit an excellent cardiovascular prognosis. Further, a lower eGFR and stress MPI results may be the predictors of cardiovascular events. Thus, patients with a lower eGFR and/or normal stress MPI results (SSS < 4) may require continuous follow-up.     

Aortic velocity propagation: A novel echocardiographic method in predicting atherosclerotic coronary artery disease burden

BackgroundThe major burden of cardiovascular disease mortality around the globe is due to atherosclerosis and its complications. Hence its early detection and management with easily accessible and noninvasive methods are valuable. Aortic velocity propagation (AVP) through color M-mode of the proximal descending aorta determines aortic stiffness, reflecting atherosclerosis. The aim of this study was to find the utility of AVP in predicting coronary artery disease (CAD) burden assessed through SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score and compared with carotid intima-media thickness (CIMT), which is an established surrogate marker of atherosclerosis.MethodsIn this cross-sectional comparative study, we measured AVP by color M-mode and CIMT by using Philips QLAB-IMT software in 100 patients, who underwent conventional coronary angiogram (CAG) between May 2013 and November 2014. Coronary artery disease is considered significant if >50% diameter stenosis is present in any epicardial coronary artery and insignificant if otherwise.ResultsInitially, to know the normal range we measured AVP and CIMT in 50 patients without any major risk factors for CAD but CAG was not done. Aortic velocity propagation ranged from 46 cm/s to 76 cm/s (mean = 58.62 ± 6.46 cm/s), CIMT ranged from 0.50 mm to 0.64 mm (mean = 0.55 ± 0.03 mm). Among 100 patients who underwent CAG we found 69% had significant CAD, 13% had insignificant CAD, and 18% had normal coronaries. Those with significant CAD had significantly lower AVP (41.65 ± 4.94 cm/s) [F (2,97) = 44.05, p < 0.0001] and significantly higher CIMT (0.86 ± 0.11 mm) [F (2,97) =35.78, p < 0.0001]. AVP had significant strong negative correlation with CIMT (r = −0.836, p < 0.0001, n = 100) and SYNTAX score (r = –0.803, p < 0.0001, n = 69), while CIMT was positively correlated with SYNTAX score significantly (r = 0.828, p < 0.0001, n = 69).ConclusionsAVP and CIMT can predict CAD burden in a robust way. AVP may emerge as an exquisite bedside tool to predict atherosclerotic burden and guide in implementing preventive therapy for cardiovascular disease.     

Effects of a fish-based diet and administration of pure eicosapentaenoic acid on brachial-ankle pulse wave velocity in patients with cardiovascular risk factors

Background and purposeBrachial-ankle pulse wave velocity (baPWV) and ratio of plasma eicosapentaenoic acid to arachidonic acid (EPA/AA ratio) are surrogate markers for coronary artery disease (CAD). We aimed to evaluate the effects of a fish-based diet and administration of EPA on baPWV and plasma EPA/AA ratio.Methods and resultsThe changes in baPWV and plasma EPA/AA ratio were compared before and after a 6-month fish-based diet in 191 patients with cardiovascular risk factors. A fish-based diet resulted in significant increment of plasma EPA/AA ratio (0.40 ± 0.18 vs. 0.49 ± 0.27, p < 0.001), with baPWV remaining unchanged. Multivariate analysis revealed that systolic blood pressure (SBP) (6-month SBP-baseline SBP) and CAD were positively associated with increased baPWV (CAD: odds ratio = 2.040, p = 0.0436, SPB: odds ratio = 1.056, p = 0.0003). When the patients were divided into three groups: CAD, low-risk, and high-risk with no prior history of CAD according to the number of risk factors at baseline, comparison among the three groups disclosed an inter-group difference in the magnitude of change in baPWV (low-risk: −35 ± 164 cm/s, high-risk: −14 ± 190 cm/s, CAD: 39 ± 164 cm/s, p = 0.0071 for trend). In 191 patients who had received a 6-month fish-based diet, 21 patients (primarily CAD patients) sequentially received high purity EPA (1800 mg/day) for 6 months. It resulted in marked increment of plasma EPA/AA ratio (0.65 ± 0.57 vs. 1.19 ± 0.46, p < 0.001), accompanied by significant reduction in baPWV (1968 ± 344 cm/s vs. 1829 ± 344 cm/s, p = 0.0061). There was a significant negative correlation between changes in baPWV and changes in plasma EPA/AA ratio in patients with a fish-based diet and sequential administration of EPA (r = −0.446, p = 0.017).ConclusionA fish-based diet was effective against increased baPWV only in low-risk patients, with slight increment of plasma EPA/AA. In high-risk patients and CAD patients, administration of EPA for preventing progression of baPWV endorsed the validity of high purity EPA administration recommended in the current guidelines.     

Le spasme coronaire lié à la dobutamine chez les patients avec des échocardiographies de stress faussement positives : prévalence et facteurs prédictifs

Background and objectiveDobutamine stress echocardiography (DSE) is being consistently used as an exercise-independent stress modality aimed at the detection of coronary artery disease (CAD) and the evaluation of myocardial ischemia. It may though occasionally induce coronary vasospasm. In this study, we aimed to evaluate the prevalence and predictors of dobutamine-related coronary spasm in patients without known CAD and false positive DSE (positive DSE but no significant coronary lesions on angiogram).MethodsThree thousand nine hundred and fifty-two patients referred to our echocardiography laboratory for DSE between January 2010 and May 2012 were prospectively investigated. Those with positive DSE underwent coronary angiograms with systematic methylergometrine intracoronary injection in case of absence of significant coronary stenosis or spontaneous occlusive coronary spasm. Patients with spontaneous occlusive coronary spasm or positive methylergometrine test but no significant stenoses were enrolled and compared with those with positive DSE but no coronary lesions nor spontaneous or induced spasm (“true” false positive DSE).ResultsTwenty-nine patients with DSE-related vasospasm (19.4% of positive DES without known CAD) were compared with 56 patients with no lesions and no spasm (“true” false positive DSE). They were more frequently smokers (72.4% vs 37.5%; P = 0.003); they had more frequently dyslipidemia (79.3% vs 43%; P = 0.001); they also had a larger ischemic area at peak DSE (3.4 segments vs 2.7 segments; P = 0.05). On multivariate analysis, dyslipidemia (HR = 10.7; 95% CI = [2.7–42.1]; P = 0.001) and active smoking (HR = 6.1; 95% CI = [1.7–21.1]; P = 0.004) were found to be independent predictors of spasm-related DSE rather than “true” false positive DSE.ConclusionDSE-related coronary spasm is present in a significant proportion of patients with erroneously labelled “false” positive DSE and should systematically be ruled out. Dyslipidemia and active smoking were independent predictors of spasm rather than “true” false positive DSE.     

Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial

Background/PurposeFamily history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Materials/MethodsBaseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%).ResultsThese patients were younger (median 56.7 vs. 62.1 years, P < 0.0001) and more often current smokers (52.4% vs. 43.5%, P < 0.0001), had more dyslipidemia (47.7% vs. 41.1%, P = 0.0003), less diabetes mellitus (14.1% vs. 17.5%, P = 0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P = 0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P = 0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P = 0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P = 0.046 and 4.8% vs. 7.7%, P = 0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI] = 1.00 [0.70, 1.44], P = 0.98).ConclusionsA family history of premature CAD is not an independent predictor of higher mortality.     

Acute effect of sildenafil on myocardial ischemic territories in patients with stable coronary artery disease

ObjectivesTo test the safety of sildenafil in patients with stable coronary artery disease (CAD).MethodsSixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/placebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS.ResultsThe baseline mean segmental PSS in the sildenafil group changed by 52%, −3 ± 1% at baseline versus −7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, −7 ± 3% at baseline versus −7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (−15 ± 4% at baseline versus −18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (−14.8 ± 2% at baseline compared to −15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake.ConclusionSildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.     

Value of conventional and tissue Doppler echocardiography in the estimation of left ventricular filling pressure

BackgroundVarious conventional and tissue Doppler parameters have been proposed for the estimation of left ventricular filling pressure.AimTo assess the utility of several conventional and tissue Doppler parameters in the estimation of left ventricular end diastolic pressure (LVEDP).MethodAmong 40 consecutive patients LVEDP was correlated with pulsed Doppler of mitral inflow and pulsed tissue Doppler of lateral mitral annulus.ResultsAmong all studied Doppler variables, E′/A′ ratio showed the most significant correlation with LVEDP (r = 0.612, p < 0.001). Among patients with grade II and III diastolic dysfunction, E′/A′ ratio showed the best correlation with LVEDP (r = 0.81, p < 0.001) with the following regression equation: LVEDP = 1.77 + (20.4 × E′/A′) while in patients with grade I diastolic dysfunction no correlation exists (r = 0.11, p = 0.63). Weak significant correlation was detected between E/E′ ratio and LVEDP (r = 0.382, p = 0.016). An E/E′ ratio > 12 had 25% sensitivity and 100% specificity to identify patients with elevated LVEDP (>15 mm Hg) with a positive predictive value of 100%. On the other hand, an E/E′ ratio of <8 had 77% sensitivity and 57% specificity to identify patients with normal LVEDP with a negative predictive value of 31%.ConclusionOf all echocardiographic variables investigated, E′/A′ ratio was identified as the best index to estimate LVEDP especially in patients with advanced LV diastolic dysfunction; a relation that was not found for other conventional or tissue Doppler variables including the E/E′ ratio.     

Evaluation of left ventricular diastolic function using tissue Doppler echocardiography and conventional doppler echocardiography in patients with subclinical hypothyroidism aged <60 years: A meta-analysis

Studies have suggested that subclinical hypothyroidism (SCH) may have detrimental effects on left ventricular (LV) diastolic function. Whether SCH is a risk factor for LV diastolic dysfunction is controversial. Databases (MEDLINE, PubMed, EMBASE) were searched for cross-sectional studies evaluating LV diastolic function in SCH patients aged <60 years using tissue Doppler echocardiography (TDE) and conventional two-dimensional Doppler echocardiography (2D-DECG) published in the past 12 years. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using fixed or random-effects models. We summarized the results of 14 cross-sectional studies with 675 participants. SCH patients had a significantly lower LV mitral annular E_a peak velocity (WMD = ?1.71 cm/s; 95%CI: ?3.02 to ?0.40; p < 0.05), E_a/A_a ratio (WMD = ?0.22; 95%CI: ?0.40 to ?0.05; p < 0.05), and significantly higher mitral annular A_a peak velocity (WMD = 0.47 cm/s; 95%CI: 0.10–0.85; p < 0.05) than euthyroid subjects using TDE. Subgroup analyses showed that statistical significance existed only in E_a and E_a/A_a parameters when data from “women ≥ 90%” were used, and in the A_a parameter when data from “women < 90%” were used. No matter which subgroup of females was used, there were significant differences in LV peak transmitral A velocity (WMD = 7.64 cm/s; 95%CI: 4.55–10.73; p < 0.05), and E/A ratio (WMD = ?0.22; 95%CI: ?0.31 to ?0.21; p < 0.05) but no significant difference in peak transmitral E velocity (p > 0.05) between SCH patients and euthyroid controls using 2D-DECG. Therefore, for those aged <60 years, SCH patients had significantly worse parameters of LV diastolic function than euthyroid controls.     

Glycated apolipoprotein B—A surrogate marker of subclinical atherosclerosis

AimsSustained hyperglycemia is a causative factor for glycation of proteins. Glycated low-density lipoprotein (LDL) is strongly associated with an increased risk of CAD (Coronary Artery Disease) in diabetics. Hence, we planned to evaluate the association of glycated apo B with subclinical atherosclerosis.MethodForty-five non obese and 45 obese diabetics were recruited. Glycated hemoglobin (HbA1c) levels were estimated by HPLC (High Pressure Liquid Chromatography) and small dense low-density lipoprotein (sdLDL) was calculated using standard formula. Plasma Insulin was done by RIA. Insulin resistance was calculated using homeostatic model assessment insulin resistance (HOMA-IR) model. Glycated apo B in serum was estimated using ELISA. Carotid intimal media thickness (CIMT) was estimated using B mode USG of carotid arteries.ResultsGlycated apo B levels were correlated significantly with fasting blood glucose (FBG) (p = 0.001), post prandial glucose (PPG) (p = 0.001), HbA1c (p = 0.013). The percent glycated apo B levels correlated significantly with FBG (p = 0.032), PPG (p = 0.004) in obese diabetic group.Multivariate regression analysis of glycated apo B and percent glycated apo B, showed that glycated apo B (p = 0.009) and percent glycated apo B (p = 0.006) were significantly correlated to FPG in diabetic population. The percent glycated apo B was also significantly correlated to PPG (p = 0.003) and sdLDL (p = 0.009). CIMT levels were higher in obese diabetics with 2 plaques positive when compared to obese non diabetic controls; however levels were not statistically significant.ConclusionPersistent hyperglycemia and sdLDL are independently associated with glycation of apo B. Presence of plaques and increased thickness of intima indicates that glycated apo B predisposes diabetics to atherosclerosis.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: The DIABHYCAR prospective study

AimVitamin D deficiency is associated with coronary artery disease (CAD), and the actions of vitamin D are mediated by binding to a specific nuclear vitamin D receptor (VDR). This study investigated the associations of VDR gene variants with CAD in two cohorts of type 2 diabetes patients.MethodsA cohort of 3137 subjects from the prospective DIABHYCAR study (CAD incidence: 14.8%; follow-up: 4.4 ± 1.3 years) and an independent, hospital-based population of 713 subjects, 32.3% of whom had CAD, were assessed. Three SNPs in the VDR gene were genotyped: rs1544410 (BsmI); rs7975232 (ApaI); and rs731236 (TaqI).ResultsIn the DIABHYCAR cohort, an association was observed between the A allele of BsmI and incident cases of CAD (HR: 1.16, 95% CI: 1.05–1.29; P = 0.002). Associations were also observed between BsmI (P = 0.01) and TaqI (P = 0.04) alleles and baseline cases of CAD. The AAC haplotype (BsmI/ApaI/TaqI) was significantly associated with an increased CAD prevalence at the end of the study compared with the GCT haplotype (OR: 1.12, 95% CI: 1.02–1.28; P = 0.04). In a cross-sectional study of the independent hospital-based cohort, associations of ApaI (P = 0.009) and TaqI (P = 0.03) alleles with CAD were observed, with similar haplotype results (OR: 1.33, 95% CI: 1.03–1.73; P = 0.03).ConclusionThe haplotype comprising the minor allele of BsmI, major allele of ApaI and minor allele of TaqI of VDR (AAC) was associated with an increased risk of CAD in type 2 diabetes patients. This effect was independent of the effects of other known cardiovascular risk factors.     

Value of mitral annular plane systolic excursion in the assessment of contractile reserve in patients with ischemic cardiomyopathy before cardiac revascularization

BackgroundMitral annular plane systolic excursion (MAPSE) is an M-mode derived echocardiographic marker of left ventricular longitudinal function, the aim of this study is to evaluate the value of MAPSE in assessment of contractile reserve in patients with ischemic cardiomyopathy before cardiac revascularization.MethodsThe study included 50 patients with ischemic cardiomyopathy with ejection fraction (EF) ≤35%, the patients presented to echocardiography laboratory for dobutamine stress echocardiography (DSE) to assess viability and contractile reserve before revascularization, patients with primary valvular disease, and those with significant mitral annular calcifications were excluded from the study. A low dose DSE was done to all patients using standardized incremental infusions of 5, 10, and 20 μg/kg/min and the following parameters were measured at both baseline and peak dose, (EF, wall motion score index(WMSI) and MAPSE). Contractile reserve was measured as the difference between the low dose and baseline values of the EF and WMSI.ResultsThe study included 50 patients aged 55.08 ± 7.15 years, 94% were males, the DSE protocol was complete in all patients without serious side effects. A total of eight hundred segments were analyzed, at baseline 65% were dysfunctional including 31.2% hypokinetic, 28.8% were akinetic, and 5% were dyskinetic. At low dose study 70% of the dysfunctional myocardium showed viability, EF increased significantly from 30.84 ± 4.56 to 42.24 ± 8.15%, p < 0.001, the WMSI reduced significantly from 1.92 ± 0.33 to 1.47 ± 0.39, and MAPSE increased significantly from 1.02 ± 0.23 to 1.30 ± 0.30 mm. MAPSE showed a significant positive correlation with EF at both baseline and low dose study (r = 0.283, p = 0.046 & r = 0.348, p = 0.013) respectively and a significant negative correlation with WMSI at both baseline and low dose study (r = −0.3, p = 0.034 & r = −0.409, p = 0.003), respectively. By ROC curve analysis we found that Δ MAPSE ≥2 mm can predict contractile reserve at Δ EF >10% (AUC = 0.6, sensitivity 67.86, specificity 59.09), and Δ MAPSE ≥1.8 mm can predict contractile reserve at ΔWMSI ≤0.20 (AUC = 0.61, sensitivity 65.5, specificity 75.6).ConclusionsMAPSE is a rapid simple quantitative echocardiographic method that can asses contractile reserve in patients with ischemic cardiomyopathy before cardiac revascularization.     

Elevated left ventricular filling pressure estimated by E/E′ ratio after exercise predicts development of new-onset atrial fibrillation independently of left atrial enlargement among elderly patients without obvious myocardial ischemia

ObjectiveTo determine whether elevated left ventricular (LV) filling pressure estimated by raised Doppler E velocity to tissue Doppler E′ velocity ratio (E/E′) after exercise is associated with increased risk of new-onset atrial fibrillation (AF) in non-ischemic elderly patients.BackgroundPrognostic importance of exercise induced LV diastolic dysfunction remains uncertain.Patients and methodsWe studied 147 elderly patients (73 ± 5 years) who underwent treadmill stress echocardiography. Patients with exercise induced LV wall motion abnormality were not included. Doppler and tissue Doppler measurements were done before treadmill exercise and immediately after the post-stress image acquisition, and E/E′ ratio was measured. Raised E/E′ was defined as E/E′ ≥ 15, and left atrial (LA) enlargement was defined as LA volume index ≥ 34 ml/m². Using Cox proportional hazards regression analysis, predictor of new-onset AF was determined. Using Kaplan–Meier analysis, we evaluated association between raised post-exercise E/E′ or LA enlargement with new-onset AF.ResultsDuring the follow-up period (median = 67 months), there were 25 new-onset AF. Cox proportional hazards regression analysis demonstrated that male gender [hazard ratio (HR) 3.294; p = 0.0117], LA enlargement (HR 3.576; p = 0.0017), and raised post-exercise E/E′ (HR 3147; p = 0.0068) were the best predictors of new-onset AF. Kaplan–Meier survival plot demonstrated that patients with both LA enlargement and raised post-exercise E/E′ developed new-onset AF most frequently. There was no significant difference in outcome between patients with isolated raised post-exercise E/E′ or isolated LA enlargement.ConclusionsRaised E/E′ ratio after exercise provides significant prognostic information for predicting new-onset AF in non-ischemic elderly patients. This prognostic value of raised post-exercise E/E′ is independent of and incremental to the LA enlargement.     

The effect of hydrochloride pioglitazone on urinary 8-hydroxy -deoxyguanosine excretion in type 2 diabetics

ObjectiveTo observe the effects of hydrochloride pioglitazone on urinary 8-hydroxy-deoxyguanosine (8OHdG) excretion in type 2 diabetics and explore its possible reno-protective mechanisms.MethodsNinety-eight uncontrolled type 2 diabetics were assigned randomly into group DP (pioglitazone add-on) and group DS (sulfonylureas add-on). At the basal and after 12 weeks treatment, FBG, HbA1c, urinary 8-OHdG, urinary albumin(ALB) and urinary creatinine (Cr) were determined, respectively.ResultsCompared with pre-treatment, FBG, HbA1c and urinary 8-OHdG /Cr ratio(U8CR) were all obviously decreased in both therapy groups; urinary albumin/urinary creatinine ratio(UACR) markedly decreased in group DP (P < 0.01), while slightly decreased in group DS (P > 0.05) after twelve weeks of observation. After 12-week treatment, UACR and U8CR in group DP were significantly lower than those in group DS (both P < 0.05) without no marked difference in FBG and HbA1c between group DP and group DS. Meanwhile, U8CR had positive correlation with UACR (r= 0.755, P < 0.01).ConclusionPioglitazone can decrease urinary 8-OHdG excretion and lighten oxidative stress in vivo in type 2 diabetics, which may play a protective role for the kidney damage.     

Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression,cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease

BackgroundA single nucleotide polymorphism (SNP) rs599839 located at chromosome 1p13.3 has previously been associated with risk of coronary artery disease (CAD) and with serum levels of low-density lipoprotein cholesterol (LDL-C). A functional link explaining the association of SNP rs599839 with LDL-C levels and CAD risk has not yet been elucidated.MethodsWe analyzed the association of rs599839 with LDL-C in 6605 individuals across a wide age spectrum and with CAD in four case–control studies comprising 4287 cases and 7572 controls. Genome-wide expression array data was used to assess the association of SNP rs599839 with gene expression at chromosome 1p13. Finally, we overexpressed sortilin in transfected cells to study LDL-uptake in vitro.ResultsEach copy of the G-allele of rs599839 associated with a decrease of serum LDL-C by 0.14 mmol/L (90% confidence interval (CI) 0.09–0.17 mmol/L, p = 2.6 × 10^?11). Moreover, each copy of the G-allele associated with a 9% decrease of CAD risk (90% CI 4–14%) in the presently studied four case–control samples and with a 13% decrease (90% CI 10–17%, p = 2.18 × 10^?9) in a pooled meta-analysis including recent genome-wide association studies on CAD. The same allele was associated with higher mRNA-expression levels of the multiligand receptor sortilin (log transformed mRNA AA vs. GG = 8.31 vs. 8.55; p = 0.01). Overexpression of SORT1 cDNA resulted in a significant increase in LDL-particle uptake (+23%, p = 0.01).ConclusionsRs599839 associates with decreased LDL-C and a lower risk of CAD. Effects appear to be mediated by increased sortilin expression and subsequently enhanced LDL-uptake into cells.