Usefulness of stress myocardial perfusion imaging and baseline clinical factors for predicting cardiovascular events in patients with prior coronary artery disease.

BACKGROUND: Stress myocardial perfusion imaging (MPI) is a well-established diagnostic and prognostic tool for coronary artery disease (CAD). However, fixed and/or reversible stress MPI defects vary considerably among patients with CAD. The usefulness of stress MPI and baseline clinical factors as independent predictors of cardiovascular events in patients with prior CAD were assessed. METHODS AND RESULTS: Stress MPI was performed in 354 patients with prior CAD. Their mean age was 71 years; the mean duration from first revascularization and/or myocardial infarction (MI) onset until stress MPI was 7.1 years; and the mean follow-up period was 34 months. Cardiovascular events were observed in 100 patients (28%), and were categorized as cardiac-related death, non-fatal MI, unstable angina, heart failure and late (>2 months from stress MPI) coronary revascularization. Multivariate Cox regression analysis revealed that peripheral arterial disease (hazard ratio [HR]=2.95; P<0.001), current smoking (HR=2.36; P=0.006), chronic kidney disease (HR=2.15; P<0.001), left ventricular ejection fraction (HR=0.98; P=0.017), and grade of myocardial ischemia assessed by stress MPI (HR=1.14; P=0.007) were independent and significant predictors of cardiovascular events. CONCLUSIONS: In patients with prior CAD, baseline clinical factors and grade of myocardial ischemia assessed by stress MPI results are significant predictors of cardiovascular events.

Coronary artery CT low-density plaque area and its ratio to the whole area of a non-calcified plaque at the culprit lesion in patients with unstable and stable coronary artery disease.

Intravascular ultrasound studies have shown that patients with unstable angina pectoris (UAP) more frequently had soft plaques in the culprit coronary arteries than patients with stable angina pectoris (SAP). We evaluated coronary plaque characteristics of culprit lesions in patients with UAP by 64-slice computed tomographic coronary angiography (64-slice CTCA). 64-slice CTCA (Aquilion 64, Toshiba Medical Systems, Otawara, Japan) was performed in 30 patients (UAP = 14, SAP = 16) before percutaneous coronary intervention (PCI). Coronary plaque area was measured by manual tracing for the difference between the area within the external elastic membrane and the area of the vessel lumen at the site of maximal luminal narrowing as observed on a cross-sectional 64-slice CTCA image where PCI was performed. Within this plaque area, CT low-density plaque area (< 50 Hounsfield units) was automatically calculated. There were no differences in stenotic rate and whole plaque area of the culprit lesion between patients with UAP and SAP. However, the CT low-density plaque area was significantly greater in patients with UAP than in those with SAP. A greater area of CT low-density plaque in the culprit lesion is associated with UAP rather than SAP. Measuring CT-low density plaque area on 64-slice CTCA images could be useful for understanding the clinical setting of UAP.

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

PURPOSE: Patients 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 SUBJECTS: Patients 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 m(2) and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction, and unstable angina. RESULTS: Cardiovascular 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). CONCLUSIONS: Patients 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.

A preliminary study of the potential role of FGF-23 in coronary calcification in patients with suspected coronary artery disease.

OBJECTIVE: The association of fibroblast growth factor 23 (FGF-23) with vascular disease in patients with preserved renal function is not well understood. The purpose of this study was to investigate the relationship of serum FGF-23 with coronary calcification in patients without chronic kidney disease and diabetes mellitus (DM). METHODS: A cross-sectional study was performed in 148 consecutive patients with suspected coronary artery disease who underwent 64-slice computed tomography coronary angiography for diagnosis of coronary artery disease. Patients with eGFR <60 mL/min/1.73 m(2), proteinuria, or DM were excluded. Associations of coronary calcification (evaluated by Agatston score) were examined with classical risk factors and with inflammatory markers, adipocytokines and FGF-23. RESULTS: The median creatinine, eGFR and FGF-23 levels were 0.7 mg/dL, 74.6 mL/min/1.73 m(2), and 26 pg/mL respectively. The strongest association was found between age and Agatston score (r = 0.367, p < 0.001) in univariate logistic regression analysis. No atherogenic risk factors, including inflammatory markers and adipocytokine levels, were associated with Agatston score. Among calcium/phosphate metabolism markers, FGF-23 showed a weak but significant correlation with Agatston score (r = 0.169, p = 0.039). In multivariate linear regression analysis, age and FGF-23 (r = 0.188, p = 0.016) were independently associated with the Agatston score. CONCLUSION: Serum FGF-23 levels were associated with coronary calcification independently of classical risk factors and of adipocytokines and inflammatory markers in patients with preserved renal function. FGF-23 may also have a direct effect on progression of coronary calcification and further studies are required to examine this issue.

Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque.

BACKGROUND: Although high-molecular-weight (HMW) adiponectin is believed to protect against atherosclerosis, the association between HMW adiponectin and the composition of coronary plaques is unknown. We evaluated whether the HMW to total adiponectin ratio was associated with the presence of coronary plaque and its composition using multi-slice computed tomography coronary angiography (MSCTCA). METHODS: Serum total and HMW adiponectin levels were measured in 53 consecutive patients (age, 71) with >50% coronary artery stenosis detected by MSCTCA. A low-attenuation coronary plaque was defined as a plaque with a mean CT density <50 Hounsfield units. Multivariate logistic regression analyses were performed to evaluate the predictors of the presence of low-attenuation coronary plaques, which is thought to be high risk, on CT. RESULTS: Decreased serum levels of total as well as HMW adiponectin were significantly associated with the presence of at least one calcified or non-calcified coronary artery plaque (total adiponectin level: odds ratio 0.76, 95% CI 0.58-0.99, P = 0.048; HMW adiponectin level: odds ratio 0.65, 95% CI 0.42-0.99, P = 0.047). A low ratio of HMW to total adiponectin was significantly associated with the presence of low-attenuation coronary plaques (4.55, 1.94-21.90, P = 0.049). However, neither the total adiponectin nor the HMW adiponectin level was associated with the presence of low-attenuation coronary plaques. CONCLUSION: Lower total or HMW adiponectin levels are associated with the presence of calcified and non-calcified coronary plaques, whereas a lower ratio of HMW to total adiponectin associated with the presence of low-attenuation coronary plaques (thought to be high risk). Measurement of total and HMW adiponectin levels and the HMW to total adiponectin ratio may be useful for risk stratification of coronary artery plaques.

The predictive value of chronic kidney disease for assessing cardiovascular events under consideration of pretest probability for coronary artery disease in patients who underwent stress myocardial perfusion imaging.

Pretest probability of coronary artery disease (CAD) facilitates diagnosis and risk stratification of CAD. Stress myocardial perfusion imaging (MPI) and chronic kidney disease (CKD) are established major predictors of cardiovascular events. However, the role of CKD to assess pretest probability of CAD has been unclear. This study evaluates the role of CKD to assess the predictive value of cardiovascular events under consideration of pretest probability in patients who underwent stress MPI. Patients with no history of CAD underwent stress MPI (n = 310; male = 166; age = 70; CKD = 111; low/intermediate/high pretest probability = 17/194/99) and were followed for 24 months. Cardiovascular events included cardiac death and nonfatal acute coronary syndrome. Cardiovascular events occurred in 15 of the 310 patients (4.8 %), but not in those with low pretest probability which included 2 CKD patients. In patients with intermediate to high pretest probability (n = 293), multivariate Cox regression analysis identified only CKD [hazard ratio (HR) = 4.88; P = 0.022) and summed stress score of stress MPI (HR = 1.50; P < 0.001) as independent and significant predictors of cardiovascular events. Cardiovascular events were not observed in patients with low pretest probability. In patients with intermediate to high pretest probability, CKD and stress MPI are independent predictors of cardiovascular events considering the pretest probability of CAD in patients with no history of CAD. In assessing pretest probability of CAD, CKD might be an important factor for assessing future cardiovascular prognosis.

Predictors of cardiovascular events in hemodialysis patients after stress myocardial perfusion imaging.

Cardiovascular prognosis in patients under normal stress myocardial perfusion images (MPI) is generally excellent. However, this is not true for patients with chronic kidney disease (CKD) treated by hemodialysis. This study evaluated prognostic factors of adverse cardiovascular events in hemodialysis patients in whom stress MPI was performed. Pharmacological stress MPI was performed in 88 hemodialysis patients, and we retrospectively followed-up for 26 months. Cardiovascular events included cardiac death, nonfatal myocardial infarction, and unstable angina. Cardiovascular events occurred in 16 patients (18%). Univariate Cox regression analysis revealed that peripheral artery disease (PAD) and parameters of stress MPI were significant predictors of cardiovascular events. Multivariate Cox regression analysis revealed that only PAD (hazard ratio=6.54; P=0.002), and abnormal stress MPI (hazard ratio=8.26; P=0.008) were independent and significant predictors of cardiovascular events. Kaplan-Meier analysis showed better prognosis in patients with normal stress MPI than in patients with abnormal stress MPI (P<0.001, log-rank test). However, in patients with normal stress MPI, cardiovascular events occurred in 10 of the 76 patients (13%). Among patients with normal stress MPI, Kaplan-Meier analysis showed that patients with no PAD had better prognosis than patients with PAD (P=0.001, log-rank test). In hemodialysis patients, both PAD and stress MPI were powerful cardiovascular predictors. Normal stress MPI alone cannot guarantee good prognosis in terms of cardiovascular events. Consideration of PAD may improve the predictive value of stress MPI in some patients.

Correlation of chronic kidney disease, diabetes and peripheral artery disease with cardiovascular events in patients using stress myocardial perfusion imaging.

OBJECTIVE: Normal stress myocardial perfusion imaging (MPI) studies generally suggest an excellent prognosis for cardiovascular events. Chronic kidney disease (CKD), diabetes and peripheral artery disease (PAD) have been established as the risk factors for cardiovascular events. However, whether these risk factors significantly predict cardiovascular events in patients with normal stress MPI is unclear. The purpose of this study was to evaluate the prognostic value of these risk factors in patients with normal stress MPI. METHODS: Patients with normal stress MPI (n = 372, male = 215 and female = 157, age = 69 years, CKD without hemodialysis = 95, diabetes = 99, PAD = 19, previous coronary artery disease = 116) were followed up for 14 months. Normal stress MPI was defined as a summed stress score of <4 and a summed difference score of <2. CKD was defined by an estimated glomerular filtration rate of <60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction and congestive heart failure requiring hospitalization. RESULTS: Cardiovascular events occurred in 20 of 372 patients (5.4%). In univariate Cox regression analysis, PAD, diabetes, diabetic retinopathy, insulin use, anemia, hypoalbuminemia, CKD, left ventricular ejection fraction and pharmacological stress tests were significant predictors of cardiovascular events. In multivariate Cox regression analysis, PAD, diabetes and CKD were independent and significant predictors for cardiovascular events, and their number was the strongest predictor for cardiovascular events (hazard ratio = 21.7, P < 0.001). CONCLUSIONS: PAD, diabetes and CKD are coexisting, independent and significant risk factors for cardiovascular events, CKD being the strongest predictor. The number of coexisting risk factors is important in predicting cardiovascular events in patients with normal stress MPI.

Impact of chronic kidney disease and stress myocardial perfusion imaging as a predictor of cardiovascular events.

BACKGROUND: Stress myocardial perfusion imaging (MPI) is an established means of predicting cardiovascular events and is suitable in chronic kidney disease (CKD) patients. We aimed to evaluate the prognostic value of CKD parameters and an abnormal stress MPI for cardiovascular events. METHODS: A total of 495 patients with suspected coronary artery disease (CAD) or history of CAD including 130 CKD patients not undergoing hemodialysis, underwent stress MPI (313 males, mean age 70 years) and were followed up for 14 months (mean period). CKD was defined as an estimated GFR of <60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiovascular events were defined as sudden cardiac death, acute coronary syndrome and congestive heart failure requiring hospitalization. RESULTS: Cardiovascular events occurred in 41 (8.3%) patients. Multivariate Cox regression analysis indicated that CKD [hazard ratio (HR) = 3.76, p < 0.001] and a stress MPI summed difference score (SDS) of ≥2 (HR = 3.78, p < 0.001) were independent predictors of cardiovascular events; CKD plus abnormal stress MPI was also a strong predictor of cardiovascular events (non-CKD and SDS <2 vs. CKD and SDS ≥2, HR = 15.9, p < 0.001). CONCLUSION: Both CKD and myocardial ischemia detected by stress MPI are independent predictors for cardiovascular events. Coexistence of CKD and myocardial ischemia detected by stress MPI is more useful for short-term risk stratification of cardiovascular events.

The impact of chronic kidney disease as a predictor of major cardiac events in patients with no evidence of coronary artery disease.

BACKGROUND: Normal stress myocardial perfusion images (MPI) generally show good prognosis for cardiovascular events. However, chronic kidney disease (CKD) is one of the important risk factors for coronary artery disease (CAD), and the interpretation of normal stress MPI has not been well established in CKD patients with no evidence of CAD. The purpose of this study was to evaluate the long-term prognostic value of stress MPI in CKD patients with no evidence of myocardial ischemia or infarction. METHODS: Patients who had no history but were suspected of CAD and had normal stress MPI (n=307, male=208, age=67 years, CKD/non-CKD=46/261) were followed-up for 4.5 years. CKD was defined as a glomerular filtration ratio of <60 ml/min/1.73 m(2) and/or persistent proteinuria. Cardiac death, non-fatal myocardial infarction, and unstable angina requiring hospitalization were defined as major cardiac events. RESULTS: Major cardiac events were observed in 3 of 261 (1.1%) non-CKD patients and 6 of 46 (13%) CKD patients (p<0.001, with log-rank test). CKD was an independent risk factor for major cardiac events (hazard ratio=13.1, p<0.001, multivariate Cox regression analysis). CONCLUSIONS: Normal stress MPI does not always promise a good prognosis for major cardiac events. Even in patients with no evidence of CAD from stress MPI, CKD can be an independent and significant risk factor for major cardiac events.