Coronary collateral circulation plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. Low High-density lipoprotein cholesterol (HDL-C) level is a strong risk factor for coronary artery disease (CAD) and is associated with poor cardiovascular outcome. It was recently reported to be associated with poor coronary collateral development in Turkish population. Hence, we investigated the influence of HDL-C on coronary collateral formation in Chinese population.
We evaluated 970 consecutive patients undergoing coronary angiography, and 501 patients with significant coronary artery disease (SCAD) were finally analyzed. The collateral scoring system developed by Rentrop was used to classify patient groups as those with poor or good collaterals.
The patients with poor collaterals had fewer diseased vessels (1.97 ± 0.84 vs 2.47 ± 0.68, p < 0.001) and lower diffuse score (2.65 ± 1.63 vs 3.76 ± 1.78, p < 0.001). There was no significant difference in HDL-C and other variables between good and poor collaterals. Multivariate analysis showed only number of diseased vessels (odd ratio 0.411, p < 0.001) was a significant predictor of poor collateral development.
The extent of CAD severity but not HDL-C level was the most powerful predictor of coronary collateral formation in our Chinese population with SCAD.
Coronary artery disease; Coronary collateral circulation; High-density lipoprotein cholesterol
Objective: Coronary collateral circulation is an alternative source of blood supply to myocardium in the presence of advanced coronary artery disease. We sought to determine which clinical and angiographic variables are associated with collateral development in patients with stable angina and chronic total coronary occlusion. Methods: Demographic variables, biochemical measurements, and angiographic findings were collected from 478 patients with stable angina and chronic total coronary occlusion. The presence and extent of collaterals supplying the distal aspect of a total coronary occlusion from the contra-lateral vessel were graded from 0 to 3 according to the Rentrop scoring system. Results: Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralizations were detected in 186 and 292 patients, respectively. Despite similar age, cigarette smoking, and medical treatment, patients with low collateralization were female in a higher proportion and less hypertensive, and had higher rates of type 2 diabetes and dyslipidemia than those with high collateralization (for all comparisons, P<0.05). In addition, patients with low collateralization exhibited more single-vessel disease, less right coronary artery occlusion, more impaired renal function, and higher serum levels of high-sensitivity C-reactive protein (hsCRP) compared with those with high collateralization. Multivariate analysis revealed that age of ≥65 years, female gender, diabetes, no history of hypertension, dyslipidemia, moderate to severe renal dysfunction, single-vessel disease, and elevated hsCRP levels were independently associated with low coronary collateralization. Conclusions: Coronary collateralization was reduced in almost 40% of stable angina patients with chronic total occlusion, which was related to clinical and angiographic factors. The impact of coronary collateralization on outcomes after revascularization needs further investigation.
Stable angina; Coronary collateral circulation; Risk factors; Angiography; Chronic total coronary occlusion
Endothelial dysfunction is thought to be a potential mechanism for the decreased presence of coronary collaterals. The aim of the study was to investigate the association between systemic endothelial function and the extent of coronary collaterals.
We investigated the association between endothelial function assessed via flow mediated dilation (FMD) of the brachial artery following reactive hyperemia and the extent of coronary collaterals graded from 0 to 3 according to Rentrop classification in a cohort of 171 consecutive patients who had high grade coronary stenosis or occlusion on their angiograms.
Mean age was 61 years and 75% were males. Of the 171 patients 88 (51%) had well developed collaterals (grades of 2 or 3) whereas 83 (49%) had impaired collateral development (grades of 0 or 1). Patients with poor collaterals were significantly more likely to have diabetes (p = 0.001), but less likely to have used statins (p = 0.083). FMD measurements were not significantly different among good and poor collateral groups (11.5 ± 5.6 vs. 10.4 ± 6.2% respectively, p = 0.214). Nitroglycerin mediated dilation was also similar (13.4 ± 5.9 vs. 12.8 ± 6.5%, p = 0.521).
No significant association was found between the extent of angiographically visible coronary collaterals and systemic endothelial function assessed by FMD of the brachial artery.
In patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. There is marked heterogeneity in the recruitment of coronary collaterals amongst patients with similar degrees of coronary artery stenoses, but the biological basis of this heterogeneity is not known. Chemokines are potent mediators of vascular remodeling in diverse biological settings. Their role in coronary collateralization has not been investigated. We sought to determine whether plasma levels of angiogenic and angiostatic chemokines are associated with of the presence and extent of coronary collaterals in patients with chronic IHD.
We measured plasma concentrations of angiogenic and angiostatic chemokine ligands in 156 consecutive subjects undergoing coronary angiography with at least one ≥90% coronary stenosis and determined the presence and extent of spontaneously visible coronary collaterals using the Rentrop scoring system. Eighty-eight subjects (56%) had evidence of coronary collaterals. In a multivariable regression model, the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12, hyperlipidemia, and an occluded artery were associated with the presence of collaterals; conversely, the concentration of the angiostatic ligand CXCL11, interferon-γ, hypertension and diabetes were associated with the absence of collaterals (ROC area 0.91). When analyzed according to extent of collateralization, higher Rentrop scores were significantly associated with increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and CXCL11 (p = 0.0002), and interferon-γ (p = 0.0004).
Plasma chemokine concentrations are associated with the presence and extent of spontaneously visible coronary artery collaterals and may be mechanistically involved in their recruitment.
The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown.
A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m2, and the remaining patients were considered to be without significant CKD (eGFR ≥ 60 mL/min/1.73m2).
Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value = 50; sensitivity 75 % and specificity 75 %).
The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.
Coronary calcification; Chronic kidney disease; Coronary artery disease
Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events. We evaluated whether multidetector computed tomographic angiography (MDCTA) revealed a link between pre-dialysis CKD and coronary artery atherosclerosis.
We retrospectively analyzed 549 patients who underwent MDCTA. Patients were divided into 3 groups: normal glomerular filtration rate (GFR) (GFR >90 mL/min/1.73 m2 body surface area), mild CKD (>60GFR≤90 mL/min/1.73 m2), and moderate CKD (>30GFR≤60 mL/min/1.73 m2). Normality testing was performed to determine if continuous variables were modeled in Gaussian distribution before analysis of variance was applied. The χ2 test was used to compare GFR subgroups. Multiple linear regression was used to detect associations of total plaque score (TPS), segment involvement score (SIS), and segment stenosis score (SSS) with GFR. A model adjusted for covariates was applied.
Patients with mild CKD had a mean TPS 2.3 points higher than those with a normal GFR (P=0.002); patients with moderate CKD had a mean TPS 5.9 points higher than the referent (P <0.001). Patients with mild CKD had a mean SIS 1.1 points higher than those with a normal GFR (P=0.002); patients with moderate CKD had a mean SIS 2.4 points higher than the referent (P <0.001). Patients with mild CKD had a mean SSS 1.4 points higher than those with a normal GFR (P=0.004); patients with moderate CKD had a mean SSS 4.2 points higher than the referent (P <0.001). The use of MDCTA showed that mild and moderate pre-dialysis CKD are independent risk factors for coronary artery atherosclerosis.
Atherosclerosis/etiology; cardiovascular diseases/etiology/prevention & control; disease progression; kidney failure, chronic/complications; retrospective studies; risk factors; tomography, x-ray computed
The role of obesity as a risk factor for cardiovascular disease in patients with chronic kidney disease (CKD) is poorly understood. Waist to hip ratio (WHR) is less influenced by muscle and bone mass than body mass index (BMI). We compared WHR and BMI as risk factors for cardiac events (myocardial infarction, fatal coronary disease) in persons with CKD.
Setting and Participants
Persons with CKD, defined as a baseline estimated glomerular filtration rate between 15 and 60 mL/min/1.73m2, drawn from two community studies: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study.
Waist to Hip Ratio, Waist Circumference and Body Mass Index.
Outcomes and Measurements
Myocardial infarction and fatal coronary heart disease.
Among 1,669 participants with CKD, mean age was 70.3 years and 56% were women. Mean WHR was 0.97 ± 0.08 in men and 0.90 ± 0.07 in women; mean BMI was 27.2 ± 4.6 kg/m2. Over a mean of 9.3 years of follow-up, there were 334 cardiac events. In multivariable adjusted Cox models the highest WHR group (n=386) was associated with an increased risk of cardiac events compared with the lowest WHR group [HR (95% CI) = 1.36 (1.01–1.83]. Obesity defined by BMI >30 kg/m2 (n= 381) was not associated with cardiac events [HR (95% CI) = 0.86 (0.62–1.20)] in comparison to participants with normal BMI. The results with waist circumference were similar to those with BMI.
Absence of a gold standard for measurement of visceral fat.
WHR, but not BMI, is associated with cardiac events in persons with CKD. Relying exclusively on BMI may underestimate the importance of obesity as a cardiovascular disease risk factor in persons with CKD.
Chronic kidney disease (CKD) is associated with cardiovascular events. Adipocyte fatty acid-binding protein (A-FABP) plays an important role in atherosclerosis. We investigated whether plasma A-FABP is involved in renal function in patients with stable angina pectoris.
A total of 221 patients with significant coronary artery stenosis were enrolled after coronary angiography. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The severity of coronary stenosis was assessed using a modified Gensini score and coronary angiography. Serum A-FABP levels were determined by enzyme-linked immunosorbent assay.
Serum A-FABP levels were significantly correlated with both eGFR (r = -0.41, p < 0.01) and the severity of coronary artery stenosis (r = 0.16, p = 0.02), and these relationships remained significant after adjusting for confounding factors. The prevalence of CKD and multi-vessel disease was significantly higher among patients with serum A-FABP levels above the median value of 20.3 ng/ml than among patients with serum A-FABP levels below the median value (57% vs. 27%, p < 0.01 and 64% vs. 48%, p = 0.02, respectively). Multivariate analysis revealed that the presence of three-vessel disease in comparison with single-vessel disease was independently associated with the higher A-FABP (per doubling) (odds ratio; 2.26, 95% confidential interval; 1.28-3.98, p < 0.01) and tended to be associated with the lower eGFR (p = 0.06).
Serum A-FABP may have a significant role in the interplay between renal dysfunction and coronary atherosclerosis.
Adipocyte; Fatty acid-binding protein; Renal dysfunction; Coronary artery disease
The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.
In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m2. The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.
Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.
Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD.
Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp298 variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions.
We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques.
Collateral development was lower in patients carrying the Asp298 variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 ± 0.08 and 2.89 ± 0.08, respectively, p = 0.04; recipient filling grade: 3.00 ± 0.08 and 3.24 ± 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp298 variant (p = 0.03) while the Asp298 variant was the sole variable independently associated with the recipient filling grade (p = 0.03).
Collateral development is lower in patients with the Asp298 variant. This may be explained by the decreased NOS activity in patients with the Asp298 variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development.
Background and Objectives
Cardiovascular disease is prevalent in chronic kidney disease (CKD). Uric acid is increased in subjects with CKD and has been linked with cardiovascular mortality in this population. However, no study has evaluated the relationship of uric acid with angiographically proven coronary artery disease (CAD) in this population. We therefore investigated the link between serum uric acid (SUA) levels and (i) extent of CAD assessed by the Gensini score and (ii) inflammatory parameters, including C-reactive protein (CRP) and pentraxin-3, in patients with mild-to-moderate CKD.
Material and Methods
In an unselected population of 130 patients with estimated glomerular filtration rate (eGFR) between 90 and 30 ml/min/1.73 m2, we measured SUA, serum pentraxin-3, CRP, urinary protein-to-creatinine ratio, lipid parameters and the severity of CAD as assessed by coronary angiography and quantified by the Gensini lesion severity score.
The mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively. The Gensini scores significantly correlated in univariate analysis with gender (R = −0.379, p = 0.02), uric acid (R = 0.42, p = 0.001), pentraxin-3 (R = 0.54, p = 0.001), CRP (R = 0.29, p = 0.006) levels, eGFR (R = −0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with smoking status, diabetes mellitus, and lipid parameters. After adjustments for traditional cardiovascular risk factors, only uric acid (R = 0.21, p = 0.02) and pentraxin-3 (R = 0.28, p = 0.01) remained significant predictors of the Gensini score.
SUA and pentraxin-3 levels are independent determinants of severity of CAD in patients with mild-to-moderate CKD. We recommend a clinical trial to determine whether lowering uric acid could prevent progression of CAD in patients with CKD.
Chronic kidney disease; Coronary artery disease; Uric acid; Pentraxin-3
Both end-stage and milder stages of chronic kidney disease (CKD) are associated with an increased risk of adverse cardiovascular events. Several studies found an association between decreasing renal function and increasing coronary artery calcification, but it remains unclear if this association is independent from traditional cardiovascular risk factors. Therefore, the aim of this study was to investigate whether mild to moderate CKD is independently associated with coronary plaque burden beyond traditional cardiovascular risk factors.
A total of 2,038 patients with symptoms of chest discomfort suspected for coronary artery disease underwent coronary CT-angiography. We assessed traditional risk factors, coronary calcium score and coronary plaque characteristics (morphology and degree of luminal stenosis). Patients were subdivided in three groups, based on their estimated glomerular filtration rate (eGFR) Normal renal function (eGFR ≥90 mL/min/1.73 m2); mild CKD (eGFR 60–89 mL/min/1.73 m2); and moderate CKD (eGFR 30–59 mL/min/1.73 m2).
Coronary calcium score increased significantly with decreasing renal function (P<0.001). Coronary plaque prevalence was higher in patients with mild CKD (OR 1.83, 95%CI 1.52–2.21) and moderate CKD (OR 2.46, 95%CI 1.69–3.59), compared to patients with normal renal function (both P<0.001). Coronary plaques with >70% luminal stenosis were found significantly more often in patients with mild CKD (OR 1.67 (95%CI 1.16–2.40) and moderate CKD (OR2.36, 95%CI 1.35–4.13), compared to patients with normal renal function (both P<0.01). After adjustment for traditional cardiovascular risk factors, the association between renal function and the presence of any coronary plaque as well as the association between renal function and the presence of coronary plaques with >70% luminal stenosis becomes weaker and were no longer statistically significant.
Although decreasing renal function is associated with increasing extent and severity of coronary artery disease, mild to moderately CKD is not independently associated with coronary plaque burden after adjustment for traditional cardiovascular risk factors.
The objective of this scientific work was to evaluate the extent and severity of perfusion abnormalities on myocardial perfusion scintigraphy (MPS) at rest and with sublingual nitroglycerine, in relation to the presence and anatomical location of collaterals demonstrated by selective coronary angiography (SCA). Twenty-eight patients with unstable angina underwent selective coronary angiography. Eighteen of them were diagnosed with myocardial infarction (MI) 2–15 days prior to examination. Presence or absence of collaterals was noted, with anatomical depiction of donor and recipient arteries as well as evaluation of degree of collateral flow. As an inclusion criterion, collateral flow had to be grade 2 (partial epicardial filling of the occluded artery) or 3 (complete epicardial filling of the occluded artery) in accordance with the Rentrop collateral flow classification. Flow was noted as follows: Complete antegrade (CA), complete retrograde (CR), partial antegrade (PA), and partial retrograde (PR). Myocardial perfusion scintigraphy using Tc-99m Sestamibi at rest and after sublingual administration of nitroglycerine was performed according to a 2-day protocol. Perfusion abnormalities, which were quantified using the 20-segments model and visual 5-point system (0, normal perfusion; 4, absent perfusion), were analyzed according to donor's and recipient's territories, as well as territories with limited or without collateral flow (PA/PR, grade 0–1 flow). A total of 84 arteries were analyzed, with stenosis in 79 of them. Arteries were divided into three groups: Donors (group I), recipients (group II), and arteries with limited or without collaterals (group III). In group I, there were 28 donor arteries, with mean severity of stenosis 71.3 ± 0.65%. In group II, there were 36 recipient arteries and mean severity of stenosis was 94.8 ± 0.26%. In group III, there were 20 arteries, and all of them had either no or poorly developed collaterals (mean severity of stenosis 60.4 ± 2%). In 3 cases, 2 donor arteries gave collaterals to 1 recipient artery, while in 11 cases, a single donor artery gave collaterals to 2 recipient arteries, and in 11 cases there was 1 donor to 1 recipient artery. A total of 1120 MPS segments were analyzed (560 at rest and 560 after nitroglycerine). The number of segments in groups I, II, and III were 204, 242, and 144, respectively. Mean number of segments per donor artery was 7.2 ± 0.7, mean number of segments per recipient artery was 7.0 ± 0.3, and mean number of segments in the territory of arteries without collaterals was 5.5 ± 0.5. In the territory of donor arteries, the mean number of segments with normal, decreased, and absent perfusion at rest was 1.6 ± 0.07, 5.67 ± 0.07, and 0.6 ± 0.03, respectively. After nitroglycerine administration, the mean number of above-mentioned segments was 1.2 ± 0.07, 6.07 ± 0.06, and 2.3 ± 0.06, respectively. There was no significant difference in the mean number of segments with normal and decreased perfusion at rest and after nitroglycerine administration (P = 0.4). However, the increase of mean segments with absent perfusion that appeared after nitroglycerine administration in donor arteries was statistically significant in comparison to MPS at rest (P < 0.0001). In the territory of recipient arteries, there was statistically significant increase in the mean number of segments with normal perfusion from 0.5 ± 0.02 at rest to 2.7 ± 0.06 with nitroglycerine (P < 0.0001), decrease in mean number of segments with decreased perfusion from 6.5 ± 0.06 at rest to 4.19 ± 0.06 with nitroglycerine (P < 0.0001), and decrease in the mean number of segments with absent perfusion from 2.3 ± 0.06 to 0.7 ± 0.03 (P = 0.003). In Group III, there was increase in mean segments with normal perfusion from 2.4 ± 0.5 to 3.2 ± 0.5, decrease in mean segments with decreased perfusion from 3.15 ± 0.5 to 2.35 ± 0.5, and absent tracer uptake from 1.1 ± 0.5 to 0.45 ± 0.3. However, these changes were not statistically significant (P = 0.3, P = 0.4, and P = 0.2, respectively). There was also statistically significant improvement of perfusion in the recipient territories from mean severity score at rest of 2.67 ± 0.08 to 1.6 ± 0.09 with nitroglycerine (P < 0.0001), in territories of poorly collateralized arteries from mean severity score at rest of 1.5 ± 0.14 to 0.8 ± 0.12 with nitroglycerine (P < 0.0008), as well as significant deterioration of myocardial perfusion in donor artery territories from mean severity score at rest of 1.7 ± 0.06 to 2.4 ± 0.06 with nitroglycerine (P < 0.0001). Based on the results of the study, we concluded that nitroglycerine administration in patients with multiple vessel coronary artery disease and well-developed collaterals can reduce myocardial perfusion to the areas supplied by donor arteries, even resulting in apparent absent perfusion, probably due to “steal syndrome,” although these arteries were less stenosed angiographically and deemed viable on MPS at rest. It appears that MPS in patients on nitroglycerine medication may result in an inappropriate decision by interventionists and surgeons to forgo revascularization. Hence, in cases where large and severe perfusion abnormalities are noted, MPS should be repeated after omitting nitrates.
Collaterals; myocardial perfusion scintigraphy; nitroglycerine; selective coronary angiography; unstable angina
Studies have documented an association between chronic kidney disease (CKD) and increased risk of end-stage renal disease (ESRD), death and comorbidities, including cardiovascular disease and metabolic syndrome, in the general population. However, there is little data on the relationship between CKD and ADE (AIDS defining event), and to our knowledge, no studies have analyzed death as a competing risk for ADE among HIV-infected persons. An observational cohort study was performed to determine the incidence and risks for developing an ADE or death among HIV-infected persons with and without CKD from 1998 – 2005. CKD was defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 using the CKD-Epidemiology Collaboration (CKD-EPI) equation. Log rank test and Cox regression which determined time to development of ADE and/or death as combined and separate outcomes, and competing risk models for ADE versus mortality, were performed. Among the 2,127 persons that contributed to the 5,824 person years of follow-up: 22% were female, 34% African-American, 38% on HAART, and 3% had CKD at baseline. ADE occurred in 227 (11%) persons and there were 80 (4%) deaths. CKD was not significantly associated with ADE/death (HR 1.3, 95% CIs: 0.5, 3.2), ADE (HR 1.0, 95% CIs: 0.4, 3.1), or death (HR 1.6, 95% CIs: 0.4, 3.1). Competing risk analyses confirmed no statistically significant associations between CKD and these outcomes. CKD was uncommon in HIV-infected persons presenting for care in this racially diverse cohort, and was not independently associated with risk of developing an ADE or dying during follow-up.
HIV; CKD; AIDS defining event (ADE); mortality
Background and Objectives
Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). We sought to compare different coronary stents used during primary PCI in patients with ST-elevation myocardial infarction (STEMI) and CKD.
Subjects and Methods
We selected 2408 consecutive STEMI patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing primary PCI and divided them into 5 groups based on the type of stent implanted: 1) bare metal stent (BMS), 2) paclitaxel-eluting stent (PES), 3) sirolimus-eluting stent (SES), 4) zotarolimus-eluting stent (ZES), or 5) everolimus-eluting stent (EES). The study endpoint was the number of major adverse cardiac events (MACE) at 12 months.
There was no significant difference in the incidence of 12-month myocardial infarction, target lesion revascularization, or target vessel revascularization between stent groups; however, the overall rate of repeat revascularization differed significantly between groups. All-cause death differed significantly among the groups. The incidence of 12-month MACE in BMS, PES, SES, ZES, and EES was 8.3%, 9.8%, 8.6%, 5.5%, and 2.6%, respectively (p<0.001). Kaplan-Meier analysis did not show a significant differences in 12-month MACE-free survival among the groups (log-rank p=0.076). This finding remained the same after adjusting for multiple confounders (p=0.147).
Any of the 5 stents can be used to treat STEMI patients with CKD undergoing primary PCI; all have similar risk of 12-month MACE. This result is hypothesis-generating and warrants further evaluation with a long-term randomized study.
Myocardial infarction; Stents; Angioplasty; Kidney failure, chronic
Diabetes mellitus (DM) and hypertension (HTN) are leading joint risk factors for both cardiovascular disease (CVD) and chronic kidney disease (CKD). In the nationwide KEEP (Kidney Early Evaluation Program) an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or a urine albumin:creatinine ratio ≥30 mg/g (3.4 mg/mmol) defines CKD. Overall in KEEP, the rates of identified CKD and self-reported CVD are 25.7% and 22.1%, respectively. The presence of CKD has been associated with younger ages of self-reported myocardial infarction and stroke. The combination of CVD and CKD in KEEP has been associated with shorter survival time. Finally, the presence of CVD or a prior history of coronary revascularization has been associated with modestly better rates of CVD risk factor control; however, the majority of patients with CKD have suboptimally controlled blood pressure, glucose, or lipids. These data suggest that patients with CKD are not only at higher risk for CVD and subsequent mortality, but are also ideal for targeted community—and practice-based interventions to improve risk factor control and, hopefully, reduce rates of subsequent cardiovacular events.
Cardiovascular disease; Chronic kidney disease; Atherosclerosis; Myocardial infarction; Percutaneous coronary intervention; Microalbuminuria; Bypass surgery; Risk factors
Coronary artery calcification (CAC) has been described in individuals with chronic kidney disease (CKD), and its presence is associated with an increased risk of cardiovascular death. However, it is unclear whether there is an independent relationship between renal function and CAC. Therefore, we evaluated the association between renal function and CAC.
Materials and Methods
We retrospectively reviewed 870 Korean patients who had undergone computed tomographic coronary angiography. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study formula with an ethnic factor for the Korean population. The CKD stages were classified using estimated GFR (eGFR) and proteinuria.
The mean age of the participants was 56.8±11.8 years, and the mean eGFR was 89.4±16.5 mL/min/1.73 m2. Hypertension and diabetes were noted in 41.5 and 17.0% of patients, respectively. There were 584 and 286 patients with no CAC and with CAC, respectively. After adjusting for confounding variables, late stage CKD was associated with CAC [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.05-7.46]. However, early stage CKD was not associated with CAC (OR 1.61, 95% CI 0.92-2.82). Diabetes was an independent risk factor of CAC (OR 2.06, 95% CI 1.36-3.13). There was no significant association between proteinuria and CAC (OR 1.65, 95% CI 0.96-2.85).
CAC is related to late stage CKD in nondialyzed patients. These findings emphasize that individuals with CAC should be considered a high-risk population for decreased renal function.
Chronic kidney disease; coronary artery calcification; proteinuria; renal function
Enhancement of coronary collateral function is an intriguing approach to the preservation of ischaemic myocardium. Coronary collateral development consists of collateral recruitment and collateral growth. Collateral growth encompasses proliferation of capillaries in the ischaemic area (angiogenesis) and maturation of pre-existing collateral vessels (arteriogenesis), with the latter being more relevant in humans. Therefore, treatment intended directly for arteriogenesis of collateral vessels appears to be more effective. Promotion of coronary collateral growth has many attractive features, particularly in patients with angina who are not indicated for percutaneous coronary intervention or coronary artery bypass grafting surgery. A complete elucidation of the remaining practical and mechanistic questions of arteriogenesis may lead to a new remedy capable of developing collateral vessels more effectively.
coronary collaterals; ischaemia; angiogenesis; arteriogenesis
Sixty-five patients with angiographically documented coronary artery disease were investigated by thallium-201 (201Tl) scintigraphy to determine the role of the collateral circulation during dynamic exercise. Fifty-three patients had complete proximal occlusion of at least one major coronary artery. One patient had total occlusion of all three major coronary arteries. Sixty-four collateral channels were identified, graded, and compared with corresponding regions of the myocardial scintigram. Tracer uptake was also graded and classified as various degrees of protection from ischaemia. A significant correlation between good collaterals with complete protection and poor or absent collaterals with no protection was noted. Seventeen patients (20 occluded vessels) had total coronary occlusion without myocardial infarction. Collaterals conferred protection in 9/15 occlusions whereas no protection was seen in five occlusions without collaterals. There was no difference in the protective role of homocoronary and heterocoronary collateral vessels. Hypertrophy of the first septal left anterior descending perforator conferred significant protection from ischaemia in contrast to bridging collaterals and ghosting. During exercise the right coronary bed is preferentially protected from ischaemia, in contrast to the left anterior descending territory. This probably reflects the direction of a transmural flow gradient between left and right ventricles during exercise.
Patients with chronic kidney disease (CKD) have a disproportionate burden of coronary artery disease and commonly undergo revascularization. The role and safety of percutaneous coronary intervention (PCI) using drug eluting stents (DES) verses bare metal stents (BMS) in CKD patients not on renal replacement therapy has not been fully evaluated. This study investigated the efficacy and safety of DES in patients with CKD not on renal replacement therapy. Patients where drawn from the National Heart, Lung, and Blood Institute Dynamic Registry and were stratified by renal function based on estimated glomerular filtration rate (GFR). Of the 4157 participants, 1108 had CKD (“low-GFR” <60 ml/min/1.73m2), while 3049 patients had normal renal function (“normal-GFR”≥60 ml/min/1.73m2). For each strata of renal function, we compared the risk of death, myocardial infarction (MI), or repeat revascularization between subjects who received DES and BMS at the index procedure. Patients with low-GFR had higher one-year rates of death and MI and a decreased rate of repeat revascularization when compared to patients with a normal-GFR. The use of DES was associated with a decreased need for repeat revascularization in the normal-GFR group (adjusted hazard ratio [HR] 0.63, 95% CI 0.50–0.79, p<0.001) but not in the low-GFR group (HR 0.69, 95% CI 0.45–1.06, p=0.09). The risks of death and MI were not different between the two stents in either patient population. In conclusion, the presence of CKD predicted poor outcomes after PCI with high rates of mortality regardless of stent type. The effect of DES in reducing repeat revascularization appeared to be attenuated in these patients.
Drug-eluting; Bare metal; Stents; Renal dysfunction
The metabolic syndrome (MS) is associated with an increased cardiovascular risk. Patients with the MS have endothelial dysfunction, decreased circulating adiponectin, and a high expression of angiogenic inhibitors such as plasminogen activator inhibitor-1 (PAI-1). We hypothesized that such patients, in the event of a coronary occlusion, might exhibit a less developed collateral circulation.
Methods and results
Three hundred and eighty-seven consecutive patients with at least one coronary occlusion of a major coronary vessel at diagnostic angiography were prospectively enrolled. Collateral development was graded with validated angiographic methods. The MS was defined according to the ATP-III definition. Fasting glucose, adiponectin, insulin concentrations, and PAI-1 were measured at the time of angiography. MS was associated with less developed collateral vessels (P = 0.005). In multivariable analysis adjusting for potential confounding factors including the duration of coronary occlusion (P = 0.0001), fasting glycaemia (P = 0.0007), low adiponectin concentration (P = 0.01), insulin-resistance (HOMA-IR; P = 0.01), high circulating PAI-1 concentration (P = 0.01), and hypertension (P = 0.008) were independently associated with poor coronary collateral vessel development.
This study shows that in patients with coronary occlusion, collateral circulation is impaired in patients with the MS. This association is partly related to fasting glycaemia and to key parameters linked to insulin resistance.
Angiogenesis; Collateral circulation; Coronary disease; Diabetes mellitus; Fibrinolysis; Insulin
Circulating matrix metalloproteinase (MMP)-2, -3 and -9 are well recognized in predicting cardiovascular outcome in coronary artery disease (CAD), but their risks for chronic kidney disease (CKD) are lacking. Therefore, the present study aimed to investigate whether circulating MMP levels could independently predict future kidney disease progression in non-diabetic CAD patients.
The prospective study enrolled 251 non-diabetic subjects referred for coronary angiography, containing normal coronary artery (n = 30) and CAD with insignificant (n = 95) and significant (n = 126) stenosis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. eGFR decline rate was calculated and the primary endpoint was a decline in eGFR over 25% from baseline.
The eGFR decline rate (ml/min/1.73 m2 per year) in patients with CAD (1.22 [−1.27, 1.05]) was greater than that in those with normal coronary artery (0.21 [−2.63, 0.47], P<0.01). The circulating MMP-2, -3 and -9 were independently associated with faster eGFR decline among CAD patients. The mean follow-up period was 8.5±2.4 years, and 39 patients reached the primary endpoint. In multivariate Cox regression model, the adjusted hazard ratios of MMP-2 ≥861 ng/mL, MMP-3 ≥227 ng/mL and MMP-9 ≥49 ng/mL for predicting CKD progression were 2.47 (95% CI, 1.21 to 5.07), 2.15 (1.12 to 4.18), and 4.71 (2.14 to 10.4), respectively. While added to a model of conventional risk factors and baseline eGFR, MMP-2, -3 and -9 further significantly improved the model predictability for CKD progression (c statistic, 0.817). In the sensitivity analyses, the results were similar no matter if we changed the endpoints of a decline of >20% in eGFR from baseline or final eGFR < 60 mL/min/1.73 m2.
Circulating MMP-2, -3 and -9 are independently associated with kidney disease progression in non-diabetic CAD patients and add incremental predictive power to conventional risk factors.
It is increasingly evident that patients with chronic kidney disease (CKD) are more likely to die from heart disease than kidney failure. This study evaluated whether pre- dialysis CKD is an independent risk factor for coronary artery calcium (CAC).
A total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR) (GFR > 90 mL/min/1.73 m2), mild CKD (90 ≥ GFR > 60 mL/min/1.73 m2), and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m2). Continuous and categorical variables were compared using analysis of variance and the χ2 statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10) was performed and odds of incidence of CAC (>10) were calculated among the three GFR subgroups.
After adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048), while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001). After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3–3.7, P = 0.004) and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9–14.3, P < 0.001) to have incident CAC compared with the group with normal GFR.
Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC.
kidney disease; coronary artery disease; atherosclerosis; calcium
Microvascular disease is a major pathogenic factor for chronic kidney disease (CKD) in persons with diabetes, but the role of microvascular disease in the development of CKD in the general population is unclear. The aim of this study is to examine whether microvascular disease precedes the development of CKD stage 3 in participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Population-based cohort study.
Setting & Participants
MESA is a prospective cohort study of adults aged 45-84 years living in 6 US communities; 4,594 adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 when they underwent retinal photography (visit 2: in 2002-2004) were examined.
Retinal microvascular caliber measured from fundus photographs.
Incident CKD stage 3 (ie, eGFR <60 mL/min/1.73 m2) at 2 subsequent follow-up examinations (visit 3 in 2004-2005, and visit 4 in 2005-2007) and an annual eGFR decrease >1 mL/min/1.73 m2 computed using the CKD Epidemiology Collaboration (CKD-EPI) equation.
After a median follow-up of 4.8 years, there were 232 incident CKD stage 3 cases. Overall, retinal microvascular caliber was not associated with incident CKD stage 3. However, in race-stratified analysis, narrower arterioles in whites was associated with a higher risk of developing CKD stage 3 after adjusting for age, sex, blood pressure, diabetes, and other factors (HR, 1.78; 95% CI, 1.01-3.15; P = 0.04, lowest vs highest arteriolar caliber tertile). This association was seen even in whites without hypertension and diabetes (HR, 2.95; 95% CI, 1.10-7.98; P = 0.03). Retinal arteriolar caliber was not associated with incident CKD stage 3 in African Americans, Chinese, or Hispanics.
Analyses were based on a single eGFR measurement, and retinal microvascular caliber and eGFR measurements were not ascertained concurrently.
Microvascular changes as manifest in the eye may contribute to the development of CKD stage 3 in whites.
Microvascular changes; retinal microvascular caliber; chronic kidney disease
Metabolic syndrome and its components are associated with chronic kidney disease (CKD) development. Insulin resistance (IR) plays a central role in the metabolic syndrome and is associated with increased risk for CKD in nondiabetic patients. IR is common in patients with mild-to-moderate stage CKD, even when the glomerular filtration rate is within the normal range. IR, along with oxidative stress and inflammation, also promotes kidney disease. In patients with end stage renal disease, IR is an independent predictor of cardiovascular disease and is linked to protein energy wasting and malnutrition. Systemic inflammation, oxidative stress, elevated serum adipokines and fetuin-A, metabolic acidosis, vitamin D deficiency, depressed serum erythropoietin, endoplasmic reticulum stress, and suppressors of cytokine signaling all cause IR by suppressing insulin receptor-PI3K-Akt pathways in CKD. In addition to adequate renal replacement therapy and correction of uremia-associated factors, thiazolidinedione, ghrelin, protein restriction, and keto-acid supplementation are therapeutic options. Weight control, reduced daily prednisolone dosage, and the use of cyclosporin decrease the risk of developing new-onset diabetes after kidney transplantation. Improved understanding of the pathogenic mechanisms underlying IR in CKD may lead to more effective therapeutic strategies to reduce uremia-associated morbidity and mortality.