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1.  A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention 
Human Molecular Genetics  2011;20(23):4748-4757.
Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5–25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ∼550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case–control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (Pcombined = 1.11 × 10−7) and rs9804922 (Pcombined = 1.45 × 10−6), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, Padditive = 0.007; rs9804922, Padditive = 0.013) and GENDER (rs10861032, Padditive = 0.005; rs9804922, Padditive = 0.023). Further analysis suggests that this locus could be involved in regulatory functions.
doi:10.1093/hmg/ddr389
PMCID: PMC3209827  PMID: 21878436
2.  Ischemic patterns assessed by positron emission tomography predict adverse outcome in patients with idiopathic dilated cardiomyopathy 
Journal of Nuclear Cardiology  2009;16(5):769-774.
Background
Although patients with idiopathic dilated cardiomyopathy (DCM) have no coronary artery disease, regional impairment of myocardial perfusion combined with preserved metabolism has been found using positron emission tomography (PET). Our aim was to assess the prognostic relevance of PET-mismatch between stress myocardial perfusion and glucose uptake on clinical outcome in DCM.
Methods
In 24 patients with DCM who underwent both myocardial perfusion and metabolism PET scanning, “mismatch” was assessed and the association with clinical outcome (hospitalization, mortality, and heart transplantation) was investigated.
Results
Mismatch was found in 16 patients (66.7%). Univariate analysis showed that the presence of mismatch was associated with adverse outcome (P = 0.03). After adjustment for sex and age, the association remained significant with an adjusted relative risk of 10.4 (95% CI 1.1-103; P = 0.04) for death, heart transplant, or hospitalization. Univariate analysis also showed that a higher extent of mismatch was significantly associated with adverse outcome (P = 0.02). After adjusting for sex and age, the association remained significant with an adjusted relative risk of 6.5 [95% CI 1.2-36; P = 0.03] for death, heart transplantation, or hospitalization.
Conclusion
PET stress perfusion-metabolism mismatch, indicative for ischemia, is frequently found in DCM patients and related to a poorer outcome.
doi:10.1007/s12350-009-9130-9
PMCID: PMC2746307  PMID: 19649680
Heart failure; dilated cardiomyopathy; positron emission tomography; myocardial perfusion; myocardial ischemia
3.  The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes 
Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.
doi:10.1186/1475-2840-7-29
PMCID: PMC2569910  PMID: 18840258
4.  Coronary Angioplasty Induces Rise in Chlamydia pneumoniae-Specific Antibodies 
Journal of Clinical Microbiology  1999;37(4):1013-1017.
Chlamydia pneumoniae is frequently found in atherosclerotic lesions, and high titers of specific antibodies are associated with increased risk for acute myocardial infarction. However, a causative relation has not been established yet. We performed a prospective study of 93 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) to investigate whether angioplasty influences Chlamydia-specific antibody titers and whether there is an association with restenosis. Blood samples were obtained before and 1 and 6 months after angioplasty. Antibodies against chlamydial lipopolysaccharide and against purified C. pneumoniae elementary bodies were measured by enzyme-linked immunosorbent assay (ELISA). After angioplasty, the prevalence of antibodies to lipopolysaccharide rose from 20 to 26% for immunoglobulin A (IgA), from 53 to 64% for IgG, and from 2 to 7% for IgM (P = 0.021, 0.004, and 0.046, respectively). There was a rapid increase of mean antibody titers of all antibody classes within 1 month of PTCA. During the following 5 months, antibody titers decreased slightly but were still higher than baseline values. Results of the C. pneumoniae-specific ELISA were essentially the same. The rise of anti-Chlamydia antibodies was not caused by unspecific reactivation of the immune system, as levels of antibodies against cytomegalovirus did not change. Neither seropositivity nor antibody titers were related to restenosis. However, increases in mean IgA and IgM titers were restricted to patients who had suffered from myocardial infarction earlier in their lives. In conclusion, we show that PTCA induces a stimulation of the humoral immune response against C. pneumoniae. These data support the idea that plaque disruption during angioplasty might make hidden chlamydial antigens accessible to the immune system.
PMCID: PMC88642  PMID: 10074519
5.  Humoral Immune Response to Human Cytomegalovirus in Patients Undergoing Percutaneous Transluminal Coronary Angioplasty 
Possible causal relations between prior human cytomegalovirus (HCMV) infection and atherosclerosis and between HCMV reactivation and restenosis after coronary angioplasty have been suggested. We investigated patterns of antibodies directed to HCMV in 112 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and in a group of sex- and age-matched controls (blood donors without evidence of atherosclerosis). Levels of antibodies to HCMV were measured by enzyme-linked immunosorbent assay (ELISA) of serum samples drawn before and 5 weeks after PTCA. To further differentiate the humoral immune response, we specifically tested antibody reactivity towards four single HCMV proteins (IE2, p52, pp150, and pp65) by recombinant ELISAs. We found that 73% of PTCA patients and 69% of sex- and age-matched controls were seropositive for HCMV (odds ratio, 1.2 [not significant]). The corresponding odds ratios for matched pairs ranged in the recombinant ELISAs from 1.2 to 1.4. Patients had more often high titers of anti-HCMV antibodies (11 versus 4%; odds ratio = 3.3 [0.9 to 15.2]; P = 0.052) and high titers of anti-pp150 antibodies (13 versus 4%; odds ratio = 6.0 [1.3 to 38.8]; P = 0.008). Anti-HCMV immunoglobulin M antibodies were not detected in any patient. There was no evidence of acute HCMV reactivation after PTCA, since the titers of antibodies to the investigated recombinant proteins did not increase at 5 weeks after PTCA. Our results show a limited association between prior HCMV infection and coronary artery disease. We infer that positive anti-HCMV titers are not a major risk factor at the time of disease manifestation. However, this study cannot rule out a possible role of HCMV at earlier stages of the atherosclerotic process. Recombinant ELISAs provide a valuable tool for investigating the antiviral immune response.
PMCID: PMC95658  PMID: 9874662

Results 1-5 (5)