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Catheterization and Cardiovascular Interventions 02/2013; 81(3):550. · 2.29 Impact Factor
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Catheterization and Cardiovascular Interventions 12/2012; 80(7):1227. · 2.29 Impact Factor
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ABSTRACT: Inflammation lies at the base of endothelial dysfunction, eventually leading to plaque formation. The degree of inflammation
defines the “vulnerability” of plaque to rupture. Numerous strategies have been adopted to identify and eventually treat high-risk
vulnerable plaque. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as one such candidate marker of inflammation that may play a direct role in the formation of rupture-prone plaque.
Epidemiologic studies have clearly demonstrated the prognostic ability of increased Lp-PLA2 levels and their association with increased risk of future coronary and cerebrovascular events. Moreover, Lp-PLA2 might have similar predictive power for both incident coronary heart disease in initially healthy individuals as well as
for recurrent events in those with clinically manifest atherosclerosis. The latest evidence has also suggested its incremental
value for risk determination over the well-established traditional risk factors and biomarkers in patients with congestive
heart failure. These data support an integral role of Lp-PLA2 activity in lipid peroxidation and cardiovascular risk assessment. This review summarizes the current body of evidence supporting
the clinical utility of Lp-PLA2 and its future applications in cardiovascular medicine.
KeywordsLp-PLA2
-Phospholipase A2
-Cardiovascular diseases
Current Atherosclerosis Reports 04/2012; 12(2):140-144. · 2.66 Impact Factor
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Journal of Nuclear Cardiology 02/2012; 19(3):410-1. · 2.67 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P161. · 3.72 Impact Factor
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Catheterization and Cardiovascular Interventions 11/2011; 78(5):692-3. · 2.29 Impact Factor
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Catheterization and Cardiovascular Interventions 10/2011; 78(4):645-6. · 2.29 Impact Factor
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Catheterization and Cardiovascular Interventions 09/2011; 78(3):344-5. · 2.29 Impact Factor
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EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 08/2011; 7(4):487-96. · 3.29 Impact Factor
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International journal of cardiology 07/2011; 151(3):369-71. · 7.08 Impact Factor
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05/2011; 4(5):590; author reply 591-3. · 1.07 Impact Factor
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Circulation Cardiovascular Interventions 04/2011; 4(2):e14; author reply e15. · 6.06 Impact Factor
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Journal of Nuclear Cardiology 03/2011; 18(3):472-85. · 2.67 Impact Factor
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ABSTRACT: Although the use of computed tomography angiography (CTA) is considered "appropriate" to distinguish ischemic vs nonischemic etiology in patients with cardiomyopathy under the current clinical practice guideline, the evidence to support this has not been evaluated in larger scale studies. Thus, we conducted a meta-analysis of available studies published by October 2010 to address this question.
Studies evaluating the diagnostic accuracy of CTA versus invasive coronary angiography (as the gold standard) for significant coronary artery disease (CAD) detection (ischemic cardiomyopathy) in patients with no known history of CAD with significantly depressed left ventricular function (ejection fraction; EF < 35%) were selected for the meta-analysis. Sensitivity, specificity, positive, and negative likelihood ratios were calculated on per patient and per segment basis using random effects model (DerSimonian-Laird Method) for computing summary estimates and receiver operator curve (ROC) analysis for evaluating overall diagnostic accuracy.
Six studies comprising 452 patients met the selection criteria for the meta-analysis. The pooled patient population was 62 ± 3 years old, with 29% females, 16% diabetics, and 43% with a history of hypertension. Mean EF was 32% ± 1%. The pooled summary estimate of sensitivity of CTA for diagnosis of ischemic cardiomyopathy was 98% [95% confidence interval (CI); 94% to 99%] and specificity was 97% (CI 94% to 98%), yielding a negative likelihood ratio of 0.06 (CI 0.02 to 0.13) and positive likelihood ratio of 20.85 (CI 12 to 36). There was no significant heterogeneity between studies for these estimates. The receiver operator curve analysis showed a robust discriminate diagnostic accuracy of ischemic etiology with an area under curve of 0.99 (P < .00001).
CTA appears as a clinically applicable accurate diagnostic modality to exclude ischemic etiology in patients with cardiomyopathy of undetermined cause and this further supports the appropriateness of the use of CTA to determine the cause of new onset cardiomyopathy of unknown etiology.
Journal of Nuclear Cardiology 02/2011; 18(3):407-20. · 2.67 Impact Factor
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ABSTRACT: Saphenous vein graft (SVG) lesions remain amongst the most challenging lesions for percutaneous coronary intervention (PCI). It is unknown whether drug eluting stents (DES) are superior to bare metal stents (BMS) for such lesions. Our objective is to determine the safety and efficacy of DES compared with BMS for SVG lesions by performing a meta-analysis of clinical trials and observational studies.
PubMed, Cochrane Register of Controlled Trials, conference proceedings, and internet-based resources of clinical trials.
Studies comparing DES vs. BMS for SVG lesions with at least>30 patients in each study reporting the outcomes of interest [death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), and the composite of death, TVR and MI (major adverse cardiac events; MACE)] with at least 6 months clinical follow-up. The primary outcome of interest was death.
Two randomized trials, one subgroup analysis of a randomized trial and 26 observational studies comprising a total of 7,994 patients (4,187 patients in DES and 3,807 patients in BMS group) were included in the analysis. Mean follow-up duration was 21±11 months (6-48 months). In the overall population, MACE events were 19% in DES and 28% in BMS with a risk ratio (RR) of 0.7 (0.6, 0.8) P<0.00001. This effect of MACE was sustained in studies with >2 years follow-up with RR of 0.77 (0.65, 0.91) P=0.003. Death rate was 7.8% in DES and 9% in BMS with a RR of 0.82 (0.7, 0.97) P=0.02. MI rate was 5.7% in DES and 7.6% in BMS with RR of 0.72 (0.57, 0.91) P=0.007. TVR was 12% in DES and 17% in BMS with RR of 0.71 (0.59, 0.85) P=0.0002. ST was 1% in DES and 1.7 % in BMS RR of 0.61 (0.35, 1.06) P=0.08. Specifically in randomized controlled trials, DES were associated with no significant differences in overall mortality [RR=1.97; 95% confidence interval (CI), 0.17-23; P=0.58] or MI (RR=1.24; 95% CI, 0.3-5.5; P=0.78) compared with BMS.
Based on the results of this meta-analysis, DES may be considered as a safe and efficacious option for the percutaneous intervention of SVG lesions.
Catheterization and Cardiovascular Interventions 02/2011; 77(3):343-55. · 2.29 Impact Factor
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Journal of Cardiovascular Magnetic Resonance. 01/2011;
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Catheterization and Cardiovascular Interventions 01/2011; 79(1):166. · 2.29 Impact Factor
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Danish Saleheen,
Nicole Soranzo,
Asif Rasheed,
Hubert Scharnagl,
Rhian Gwilliam,
Myriam Alexander,
Michael Inouye,
Moazzam Zaidi,
Simon Potter,
Philip Haycock, [......],
Ralph McGinnis,
Frank Dudbridge,
Bernhard R Winkelmann,
Bernhard Böehm,
Simon Thompson,
Willem Ouwehand,
Winfried März,
Philippe Frossard,
John Danesh,
Panos Deloukas
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ABSTRACT: Evidence is sparse about the genetic determinants of major lipids in Pakistanis.
Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)).
Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.
Circulation Cardiovascular Genetics 08/2010; 3(4):348-57. · 6.11 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the impact of renal function by estimated glomerular filtration rate (eGFR) on risk stratification of diabetic and nondiabetic patients undergoing myocardial perfusion imaging (MPI) by single-photon emission computed tomography for suspected ischemia.
Coronary artery disease is the leading cause of death among diabetic persons; however, diabetic persons are a very heterogeneous group in terms of cardiovascular risk, necessitating further risk stratification.
Patients (n = 1,747, age 65 +/- 10 years, 37% diabetic) undergoing MPI were followed for cardiac death (CD) for a mean of 2.15 +/- 0.8 years. Chronic kidney disease (CKD) was defined by an eGFR <60 ml/min.
In the presence of a normal scan, annual CD rate was 0.9% for those with no diabetes mellitus (DM) and no CKD, 0.5% in the DM alone group, 2.35% in CKD alone, and 2.9% in those with both DM and CKD (p < 0.001). Patients with DM+CKD had a 2.7-fold risk of CD compared with no DM no CKD (p = 0.001) after controlling for age, ejection fraction, history of coronary artery disease, and other risk factors. The risk of CD increased as a function of the presence and severity of perfusion defects, regardless of CKD or DM status. Presence of CKD conferred a several-fold higher risk of CD for the various strata of perfusion defects. Log-rank test for difference in probability of CD was nonsignificant for comparison between patients with no DM no CKD and those with DM alone (p = 0.73) but was significant for comparison between patients with no DM no CKD and patients with CKD alone (p < 0.001) or DM+CKD (p < 0.001).
MPI and eGFR provide valuable risk stratification for diabetic and nondiabetic patients. Diabetic patients without CKD seem to have similar short-term cardiac outcomes compared with nondiabetic patients. Underlying CKD seems to identify a high-risk subgroup of diabetic patients.
JACC. Cardiovascular imaging 07/2010; 3(7):734-45. · 14.29 Impact Factor
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Danish Saleheen,
Myriam Alexander,
Asif Rasheed,
David Wormser,
Nicole Soranzo,
Naomi Hammond,
Adam Butterworth,
Moazzam Zaidi,
Philip Haycock,
Suzannah Bumpstead, [......],
Faisal Shahid,
Zehra Memon,
Shahzad Majeed Bhatti,
Waleed Kayani,
Syed Saadat Ali,
Muhammad Fahim,
Muhammad Ishaq,
Philippe Frossard,
Panos Deloukas,
John Danesh
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ABSTRACT: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry.
A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis.
To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.
Arteriosclerosis Thrombosis and Vascular Biology 07/2010; 30(7):1467-73. · 6.37 Impact Factor
