Glycoprotein IIb/IIIa inhibitors with or without thienopyridine pretreatment improve outcomes after primary percutaneous coronary intervention in high-risk patients with ST elevation myocardial infarction--a meta-regression of randomized controlled trials.

BACKGROUND: Recent studies have casted a doubt on usefulness of routine glycoprotein IIb/IIIA inhibitors (GPI) in patients, pretreated with aspirin and clopidogrel, undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). OBJECTIVE: We aimed to investigate the effect of relevant factors, particularly thienopyridine pretreatment, on clinical benefit from GPI in randomized controlled trials (RCT). METHODS: We searched electronic databases for RCT comparing GPI to control in patients with STEMI undergoing primary PCI. Relevant study covariates and clinical outcomes were extracted. A random effect cumulative and subgroup analyses (thienopyridine non-pretreated studies vs. pretreated studies) were performed. A weighted random effect meta-regression to determine the effect of thienopyridine pretreatment, enrollment year, control group mortality, and ischemic time on mortality benefit from GPI use was conducted. RESULTS: Twenty studies (9 non-pretreated, 11 pretreated) with a total of 7,414 patients (3,811 GPI, 3,603 control) were included. GPI use reduces mortality (risk ratio, RR = 0.75 95% confidence interval (CI) 0.57-0.97, P = 0.03), target vessel revascularization (TVR) (RR = 0.63, 95% CI 0.50-0.80, P = 0.0002), but not reinfarction (RR = 0.66, 95% CI 0.44-1.0, P = 0.05) at 30 days. There was no effect of thienopyridine pretreatment on reduction in mortality (P = 0.39), reinfarction (P = 0.46), or TVR (P = 0.95) in subgroup analysis. Meta-regression analyses showed significant effect of control group mortality risk (B = -12.15, P = 0.034) but not of thienopyridine pretreatment, enrollment year or control group ischemic time on mortality reduction from GPI use. CONCLUSION: The benefit from GPI use in primary PCI for STEMI appears to depend on mortality risk, and not on thienopyridine pretreatment.

Rare case of "wandering artery of drummond" as a result of chronic triple mesenteric vessel occlusion treated by isolated angioplasty and stenting of the inferior mesenteric artery.

We report a rare clinical scenario of chronic mesenteric ischemia (CMI) patient with obstruction of all the three major gut vessels including celiac, superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) with a sole artery supplying the collaterals through marginal artery of left colon (the "wandering artery of Drummond"). A 70-year-old man was presented to hospital with acute onset of dyspnea, diaphoresis, severe epigastric pain, nausea, and vomiting that started after lunch. Initially, patient was diagnosed and treated for non-ST elevation myocardial infarction (NSTEMI). Furthermore, work-up, including computed tomographic scan of abdomen followed by angiogram, revealed 100% obstruction of celiac and SMA, whereas inferior IMA had 90% ostial lesion with poststenotic dilatation and collaterals supplying to entire colon. Subsequently, IMA ostial lesion was stented through percutaneous intervention and patient noted significantly improved symptoms and quality of life. To conclude, percutaneous endovascular treatments confer favorable strategy for CMI, and it may either be curative or allow nutritional optimization before definitive surgery.

Zotarolimus-eluting stent versus sirolimus-eluting and paclitaxel-eluting stents for percutaneous coronary intervention: a meta-analysis of randomized trials.

BACKGROUND: The zotarolimus-eluting stent (ZES) is a new drug-eluting stent that delivers zotarolimus, a synthetic analogue of sirolimus, through a biocompatible phosphorylcholine polymer coating. ZES has shown promising results compared with bare-metal stents, but its safety and efficacy against sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents is yet to be established. AIMS: We aimed to summarize current evidence from randomized trials comparing ZES with SES and PES. METHODS: We searched the Medline, Embase and CENTRAL databases for randomized studies comparing ZES with SES and PES for percutaneous coronary intervention. Relevant clinical and angiographic outcomes were extracted and combined using random and fixed-effect models for heterogeneous and homogenous outcomes, respectively. RESULTS: Seven randomized trials met the inclusion criteria: ZES group, n=3787; SES group, n=2606; PES group, n=1966. Compared with SES, ZES was associated with significantly higher odds of clinically driven target vessel revascularization (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.78-3.14) and target lesion revascularization (OR 2.46, 95% CI 1.36-4.46). Compared with SES, ZES had higher in-stent restenosis (OR 6.13, 95% CI 3.96-9.50), late lumen loss 'in-stent' (mean difference [MD] 0.39 mm, 95% CI 0.34-0.44) and late lumen loss 'in-segment' (MD 0.18 mm, 95% CI 0.15-0.21). ZES was associated with higher in-stent late lumen loss than PES (MD 0.18 mm, 95% CI 0.07-0.28). There were no differences in mortality, reinfarction or stent thrombosis with ZES compared with SES and PES. CONCLUSION: ZES is not superior to PES and is inferior to SES in terms of angiographic outcomes and clinically driven revascularization.

Favorable effects of vasodilators on left ventricular remodeling in asymptomatic patients with chronic moderate-severe aortic regurgitation and normal ejection fraction: a meta-analysis of clinical trials.

BACKGROUND: The role of vasodilator therapy in asymptomatic patients with chronic moderate to severe aortic regurgitation (AR) and normal left ventricular (LV) function is uncertain. We assessed the effects of vasodilator therapy (hydralazine, calcium channel blockers, and angiotensin-converting enzyme inhibitors) in this subgroup of patient population. HYPOTHESIS: Vasodilators have favorable effects on LV remodelling in asymptomatic patients with chronic moderate to severe aortic regurgitation and normal LV function. METHODS: We performed a systematic literature search for randomized clinical trials using long-term vasodilator therapy in asymptomatic patients with chronic severe AR and normal LV function. The magnitude of difference between the vasodilator and nonvasodilator groups was assessed by computing the mean difference (MD). Heterogeneity of the studies was analyzed by Cochran Q statistics. The MD for LV ejection fraction, LV end systolic volume index, and LV end diastolic volume index were computed by random effects model. The MD for LV end-systolic diameter and LV end-diastolic diameter were computed by fixed effects model. A 2-sided alpha error <0.05 was considered to be statistically significant. RESULTS: Seven studies with 460 patients were included. Meta-analysis of the studies revealed a significant increase in LVEF (MD: 5.32, 95% confidence interval [CI]: 0.37 to 10.26, P = 0.035), a significant decrease in LV end diastolic volume index (MD: -16.282, 95% CI: -23.684 to -8.881, P < 0.001), and a significant decrease in LV end diastolic diameter (MD: -2.343, 95% CI: -3.397 to -1.288, P < 0.001) in the vasodilator group compared with the nonvasodilator group. However, there was no significant decrease in LV end systolic volume index (MD: -6.105, 95% CI: -12.478 to 0.267, P = 0.060) or in LV end systolic diameter (MD: 0.00, 95% CI: -0.986 to 0.986, P = 1.0) in the vasodilator group compared with the nonvasodilator group. CONCLUSIONS: In asymptomatic patients with chronic severe AR and normal LV function, vasodilators have favorable effects on LV remodeling.

Cardiovascular outcomes using intra-aortic balloon pump in high-risk acute myocardial infarction with or without cardiogenic shock: a meta-analysis.

BACKGROUND: Intra-aortic balloon pump (IABP) has been widely used ever since it was first developed in 1962 and became part of clinical practice in 1968. It is used to treat patients with complications of acute myocardial infarction (AMI) such as cardiogenic shock, refractory left ventricular failure, and for high-risk patients undergoing angioplasty and coronary artery bypass grafting. However, current literature demonstrates a significant variance in terms of indications for using IABP and its outcomes. The aim of this study is to review the existing literature to analyze whether the use of IABP offers any cardiovascular benefit to the patients with AMI and the complications associated with the use of IABP. Material and METHODS: A systematic review of literature identified 16 studies. We analyzed the primary endpoint (in-hospital mortality, reinfarction, recurrent ischemia) and secondary endpoint (incidence of moderate and severe bleeding during hospitalization at 7 days). We estimated the proportion of between-study inconsistency (heterogeneity) due to true differences between studies (rather than differences due to random error or chance) using the I2 statistic. Mantel-Haenszel fixed-effect model was used to calculate the combined relative risks (RRs) when studies were homogenous, and the random effect model was used when studies were heterogenic. A 2-sided α error <.05 was considered statistically significant. RESULTS: Meta-analysis revealed that in-hospital mortality of patients with AMI with and without cardiogenic shock did not differ between IABP group as compared to no IABP group (RR: 1.11; confidence interval [CI]: 0.69-1.78; P = .67). However, analysis of patients with AMI with cardiogenic shock showed statistically significant improvement in mortality (RR: 0.72; CI: 0.60-0.86; P < .0004). There was no significant reduction in the rate of reinfarction (RR: 0.81; CI: 0.30-2.17; P = .67) or recurrent ischemia (RR: 0.78; CI: 0.34-1.78; P = .55) using IABP. Intra-aortic balloon pump was found to significantly increase the risk of moderate bleeding (RR: 1.71; CI: 1.03-2.85; P = .04) and major bleeding (RR: 4.01; CI: 2.66-6.06; P < .0001). CONCLUSION: The present meta-analysis suggests that patients with high-risk AMI without cardiogenic shock do not seem to benefit from the use of IABP as measured by in-hospital mortality, rate of reinfarction, and recurrent angina. However, in patients with AMI with cardiogenic shock (systolic blood pressure [SBP] < 90), there was significant reduction in mortality using IABP. The use of IABP is associated with increase in the rate of both moderate and severe bleeding.

Fixing the "broken heart": pharmacologic implications.

Broken-heart syndrome also known as Left ventricular apical ballooning syndrome or Stress-induced cardiomyopathy or Takotsubo cardiomyopathy is an important clinical entity, which presents clinically, similar to acute coronary syndrome with an acute onset of chest pain, ST-T changes in electrocardiogram, and moderate cardiac enzyme elevation. Recent studies have shown that it accounts for 1%-2% of cases of ST-elevation infarction. An episode of intense emotional or physiologic stress has been reported before its presentation and is presumed to be the triggering factor in the pathogenesis. The pathophysiology of this syndrome still remains unclear, and management is mostly empiric and supportive. In this review, we have discussed various pathophysiologic mechanisms underlying this cardiomyopathy and their pharmacological implications and role of medications such as aspirin, beta blockers, angiotensin-converting enzyme inhibitors, and statins for patients presenting with this syndrome in treatment and prevention.

Drug-eluting stents versus bare metal stents in ST elevation myocardial infarction at a follow-up of three years or longer: A meta-analysis of randomized trials.

BACKGROUND: Drug-eluting stents (DES) are associated with a decreased frequency of repeat revascularization compared with bare metal stents (BMS) in patients with coronary artery disease; however, uncertainty over their long-term safety, especially in high-risk patients, such as those with ST elevation myocardial infarction (STEMI), persists. OBJECTIVE: To evaluate the safety and efficacy of DES compared with BMS in STEMI patients at a follow-up of three years or longer. METHODS: Two independent investigators systematically searched the Medline, CENTRAL, Embase and CardioSource databases for randomized trials comparing DES with BMS in STEMI, and reporting outcomes at three years or longer. Relevant study characteristics and clinical end points were extracted. Random-effect and fixed-effect models were used to calculate ORs for heterogeneous and homogenous outcomes, respectively. RESULTS: Ten randomized trials met the eligibility criteria, resulting in the inclusion of 4330 patients in the DES group and 2662 patients in the BMS group. DES use significantly reduced the odds of target vessel (OR 0.44 [95% CI 0.35 to 0.54]) and target lesion revascularization (OR 0.47 [95% CI 0.36 to 0.61]). Furthermore, patients in the DES group experienced major adverse coronary events less frequently than patients in the BMS group, which was driven mainly by the decreased revascularization rate. Although the incidence of stent thrombosis was similar, DES was associated with a higher risk of very late stent thrombosis (OR 1.69 [95% CI 1.11 to 2.57]). There were no differences between the groups with respect to death, cardiac death and myocardial infarction. CONCLUSION: DES continues to be associated with a lower repeat revascularization rate in patients with STEMI, with a small but significantly increased risk of very late stent thrombosis compared with BMS at a follow-up of three years or longer.

Tirofiban use with clopidogrel and aspirin decreases adverse cardiovascular events after percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials.

Current guidelines deemed usefulness of routine early glycoprotein IIb/IIIa inhibitor (GPI) administration in ST-elevation myocardial infarction (STEMI) before primary percutaneous coronary intervention (PCI) with dual antiplatelet therapy as uncertain. We aimed to examine the current evidence for the use of tirofiban, a nonpeptide glycoprotein IIb/IIIa inhibitor, in STEMI patients treated with dual antiplatelet therapy. We performed systematic searches of MEDLINE, EMBASE, and CENTRAL databases for randomized controlled trials (RCTs) of tirofiban use in STEMI patients treated with aspirin and clopidogrel which reported clinical and/or angiographic outcomes after primary PCI. Data were combined using random effect and fixed effect models for heterogeneous and homogeneous outcomes respectively using Review Manager 5 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2008). Six randomized controlled trials were eligible for the inclusion; involving 708 patients in tirofiban group and 721 control subjects. Routine tirofiban use decreased the major adverse cardiovascular events (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.26-0.94). Corrected thrombolysis in myocardial infarction (TIMI) frame count was also reduced with tirofiban (mean difference -8.48 [95% CI, -12.62 to -4.34]). There were no significant differences in the rates of postprocedure TIMI flow grade 3 and TIMI myocardial perfusion/blush grade 3, major bleeding by TIMI criteria, or mortality in the 2 groups. Current analysis of available studies suggests that routine and early tirofiban use before primary PCI may decrease the major cardiovascular events in STEMI patients treated with aspirin and clopidogrel without any significant increase in major bleeding. An adequately powered randomized trial is urgently needed to confirm the above findings and estimate the effect size.

Prevention of recurrent atrial fibrillation with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Controversy persists regarding the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in the prevention of recurrent atrial fibrillation (AF). We performed a meta-analysis of randomized controlled trials (RCTs), not designed a priori to test this hypothesis, to explore whether ACEs and ARBs reduce recurrent AF. METHODS: We performed a systematic literature search for RCTs using ACEIs or ARBs and providing data on the outcome of recurrent AF. Statistical heterogeneity across the trials was tested using the Cochran Q statistic and I(2) was computed to quantify heterogeneity. A 2-sided α error of less than .05 was considered statistically significant (P < .05). RESULTS: The analysis was based on 8 RCTs including 2323 patients. The Mantel-Haenszel random-effect model was used to calculate relative risk (RR) for studies using ACEIs or ARBs, and for studies using ARBs. The fixed-effect model was used to calculate RR for studies using ACEIs. Meta-analysis of the studies revealed that ACEIs or ARBs significantly reduced the incidence of recurrent AF (RR, 0.611; 95% CI, 0.441-0.847; P = .003). The RR for recurrent AF was 0.643 (95% CI, 0.439-0.941; P = .023) for studies using ARBs and 0.54 (95% CI, 0.377-0.80; P = .002) for studies using ACEIs. CONCLUSION: In this meta-analysis of RCTs not designed a priori to test the hypothesis, ACEs and ARBs were associated with a significant reduction in recurrent AF. Large-scale randomized trials designed a priori to test the hypothesis are necessary to complete the totality of evidence.

Complete versus culprit only revascularization in acute ST elevation myocardial infarction: a meta-analysis.

BACKGROUND: Current guidelines recommend against the revascularization of noninfarct related artery (complete revascularization [CR]) in patients with ST elevation myocardial infarction (STEMI) and no hemodynamic compromise, though level of evidence is C. AIM: Our aim was to examine the available evidence to determine any advantage of CR over culprit only revascularization (COR). METHODS: We systematically searched medline using key words-"culprit coronary revascularization," "complete revascularization myocardial infarction," and "multivessel STEMI" for studies reporting outcomes after COR versus CR during primary procedure or index hospitalization published in English language and indexed before February 2010. A random effect or fixed effect meta-analysis, as applicable, was performed using RevMan 5 (Cochrane Center, Denmark). RESULTS: Nine eligible nonrandomized studies amounting to 4,530 patients in CR and 27,323 patients in COR group were included. In addition, two small randomized trials were reviewed and included in secondary analysis. Majority of patients were hemodynamically stable. Major adverse cardiovascular events (Odds ratio [OR] = 0.95, 95% CI 0.47-1.90) and long term mortality (OR = 1.10, 95% CI 0.76-1.59) were similar. The marginal increased odds of in-hospital mortality was derived from a single study with no difference found after sensitivity and cumulative analysis (OR = 1.21 95% CI 0.85-1.73). CONCLUSION: Current analysis of heterogeneous studies did not reveal any benefit of CR over COR in patients with STEMI. However, also provide no conclusive evidence of increased in hospital mortality after CR. A randomized trial is needed to confirm these findings and recognize any subgroup which might benefit from CR.

Newer anticoagulants as an alternate to warfarin in atrial fibrillation: a changing paradigm.

Atrial fibrillation is the most common cardiac arrhythmia responsible for one third of the hospitalizations because of cardiac rhythm disturbances. Atrial fibrillation leads to stroke, heart failure, and other causes of mortality. Warfarin, a vitamin K antagonist, is the first-line agent for the prophylaxis of stroke in patients with atrial fibrillation. Limitations associated with warfarin have led to development of new anticoagulants targeting different sites in the coagulation cascade. A direct thrombin inhibitor, dabigatran, has been evaluated in clinical studies for prophylaxis in atrial fibrillation. Factor Xa inhibitors, direct as well as indirect inhibitors, are in various stages of development for their antithrombotic effect. This article reviews the studies done on these novel anticoagulants and their prophylactic potential for the prevention of stroke in atrial fibrillation.

Effects of statins on progression of carotid atherosclerosis as measured by carotid intimal--medial thickness: a meta-analysis of randomized controlled trials.

BACKGROUND: Carotid intimal-medial thickness (CIMT) as measured by B-mode ultrasonography is a surrogate marker for carotid atherosclerosis. Studies have found conflicting results for the effect of statins on carotid atherosclerosis progression by measuring CIMT. Hence, this meta-analysis was conducted to evaluate the impact of statin therapy on CIMT progression. METHODS: A systematic search using PubMed, EMBASE, and Cochrane library databases was performed. Heterogeneity of the studies was analyzed by the Cochran Q statistics. The significance of common treatment effect was assessed by computing common mean difference between the control and treatment groups. A 2-sided alpha error of less than 0.05 was considered to be statistically significant. RESULTS: In all, 11 trials (N = 3806) fulfilled the criteria for inclusion in the analysis. The study population included 67.2% males and 22.8% females. The mean age was 58.7 years. Treatment with statins (mean treatment duration of 25.6 months) resulted in a significant reduction in the mean low-density lipoprotein ([LDL]; mg/dL, before treatment 168.6 ± 33.3, after treatment 102.33 ± 27.9, P < .05). No significant changes in the levels of LDL cholesterol were noted in the control group. A total of 7 trials showed regression and 4 trials showed slowing of progression of CIMT. Pooled analysis of all 11 trials showed that there was a statistically significant benefit with statin therapy in slowing down the progression of CIMT and the common mean difference between statin therapy arm and placebo arm was -0.040 (CI: -0.052--0.028; P value < .001). CONCLUSIONS: Statins therapy slows down the progression of carotid atherosclerosis as measured by CIMT, indicating benefits at subclinical stage of the disease process.

Bisphosphonate use in women and the risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Bisphosphonates are used for the prevention and treatment of osteoporosis, but there have been concerns about a potential link between bisphosphonate therapy and atrial fibrillation. Data on the effects of bisphosphonate on the risk of atrial fibrillation are conflicting and the association of serious atrial fibrillation (defined as events resulting in hospitalization or disability or judged to be life-threatening) with the use of bisphosphonates is uncertain. HYPOTHESIS: We aimed to systematically evaluate the association of bisphosphonate use with the risk of atrial fibrillation. METHODS: We performed a systematic literature search for clinical trials using bisphosphonates and providing data on the outcome of atrial fibrillation. Four randomized controlled trials and 3 population based case-control studies were included in the final analysis. A meta-analysis was performed with the 4 randomized controlled trials to determine the risk of serious atrial fibrillation. RESULTS: For the purpose of meta-analysis, the studies were homogenous; therefore the Mantel-Haenszel fixed-effect model was used to calculate combined relative risk (RR). A two-sided alpha error of less than 0.05 was considered to be statistically significant (p<0.05). Four studies with 26126 postmenopausal women were included in the meta-analysis. Meta-analysis revealed that serious atrial fibrillation occurred more frequently in the bisphosphonate group compared to the placebo group (RR 1.525; 95% CI, 1.166 to 1.997; p=0.002). Two out of 3 observational studies indicated a statistically significant increase in the risk of atrial fibrillation with bisphosphonate therapy. CONCLUSIONS: Bisphosphonate use is associated with a significant increase in the risk of serious atrial fibrillation in postmenopausal women.

Safety and efficacy of prolonged use of unfractionated heparin after percutaneous coronary intervention.

The current guidelines for percutaneous coronary intervention do not address the prolonged postprocedural use of unfractionated heparin (UFH) to prevent acute occlusion. However, recently published small studies have yielded mixed results, leaving the question unanswered. Hence, we performed a meta-analysis of the existing evidence to assess the safety and efficacy of prolonged infusion of UFH after percutaneous coronary intervention. A systematic review of literature revealed seven studies involving 2412 patients. End points analyzed were ischemic complications (acute closure, myocardial infarction, and repeat revascularization) and major vascular complications (hematoma, arteriovenous fistula, pseudoaneurysm, and retroperitoneal bleed). Because the studies were homogenous for outcomes, combined relative risks across all the studies and the 95% confidence intervals were computed using the Mantel-Haenszel fixed-effect model. A two-sided alpha error <0.05 was considered to be statistically significant. There were no significant differences in patient demographics between both groups. Compared with placebo, the risk of major vascular complication was significantly higher in patients getting postprocedural UFH for prolonged hours (relative risk, 2.24; confidence interval, 1.68-3.48; P = 0.001). However, the risk of ischemic complications was similar in both groups (relative risk, 0.95; confidence interval, 0.46-1.96; P = 0.89). The meta-analysis suggests that routine infusion of UFH after uncomplicated percutaneous coronary intervention may result in increased vascular complications without any reduction in incidence of ischemic complications.

Dronedarone for atrial fibrillation: a new therapeutic agent.

Atrial fibrillation is the most common of the serious cardiac rhythm disturbances and is responsible for substantial morbidity and mortality. Amiodarone is currently one of the most widely used and most effective antiarrhythmic agents for atrial fibrillation. But during chronic usage amiodarone can cause some serious extra cardiac adverse effects, including effects on the thyroid. Dronedarone is a newer therapeutic agent with a structural resemblance to amiodarone, with two molecular changes, and with a better side effect profile. Dronedarone is a multichannel blocker and, like amiodarone, possesses both a rhythm and a rate control property in atrial fibrillation. The US Food and Drug Administration approved dronedarone for atrial fibrillation on July 2, 2009. In this review, we discuss the role of dronedarone in atrial fibrillation.

Plasma parathyroid hormone level and prevalent cardiovascular disease in CKD stages 3 and 4: an analysis from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of death in patients with chronic kidney disease (CKD). Secondary hyperparathyroidism is common in patients with CKD, and its relationship to CVD is not well defined. This analysis aims to assess whether serum intact parathyroid hormone (PTH) level is an independent risk factor for CVD in patients with CKD stages 3 and 4. METHODS: In this cross-sectional study, medical history surveys, including CVD events, were collected from 4,472 patients with stages 3 and 4 CKD identified by the National Kidney Foundation Kidney Early Evaluation Program (KEEP), which included blood pressure measurement and laboratory testing. Age, hemoglobin level, estimated glomerular filtration rate, serum phosphorus level, and serum calcium level were evaluated as continuous variables, and plasma PTH levels, by tertile: less than 35, 35 to 70, and greater than 70 pg/mL. Multivariate logistic regression was used to estimate odds ratios (ORs) of CVD predictor variables. RESULTS: Mean age was 68.3 +/- 11.8 years. Of the study population, 68% were women, 69% were white, 6% were current smokers, 45% were obese, 46% had diabetes, and 83% had hypertension. A history of CVD was present for 1,972 (44.1%), and plasma PTH level greater than 70 pg/mL, for 2,239 (50.1%). Multivariate logistic regression showed ORs for CVD events increasing with age (OR, 1.03; P < 0.001), male sex (OR, 1.51; P < 0.001), diabetes (OR, 1.73; P < 0.001), hypertension (OR, 1.43; P < 0.001), and intact PTH level greater than 70 pg/mL (OR, 1.51; P < 0.001; reference, <35 pg/mL). CONCLUSIONS: PTH level greater than 70 pg/mL is independently associated with CVD events in patients with CKD stages 3 and 4. No association was observed between serum phosphorus or calcium level and CVD events. These findings provide support for intact PTH testing, along with testing for other indicators of CKD mineral and bone disorders, at earlier CKD stages.