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Biomedical subjects

Deepak L Bhatt

Publications and source records attributed to Deepak L Bhatt.

At least 19 recordsLinked to original sources

Prediction of incident heart failure in established atherosclerotic cardiovascular disease: the SMART2-HF model.

BACKGROUND AND AIMS: Patients with established atherosclerotic cardiovascular disease (ASCVD) are at high risk of developing heart failure (HF). However, incident HF is not part of the risk assessment of current guideline-recommended models. The aim of this study was to develop and externally validate the SMART2-HF model for prediction of incident HF in patients with ASCVD. METHODS: SMART2-HF was developed in 7698 individuals with established ASCVD (coronary, cerebrovascular, or peripheral artery disease, or abdominal aortic aneurysm) but without prior HF from the UCC-SMART cohort. Cox proportional hazards models including sex-predictor interactions and with age as the time scale were derived to estimate the 10-year and lifetime risk of incident HF (hospitalization for HF or HF-related death), accounting for competing non-HF mortality. Predictors, limited to routinely available clinical characteristics, were aligned with the SMART2 risk model for recurrent cardiovascular (CV) risk in the same population. External validation was performed in 240 741 patients with ASCVD from six data sources: the Clinical Practice Research Datalink, the HUNT3 study, the SWEDEHEART Registry, the ASCVD-Particles cohort, the Estonian Biobank and the international REACH Registry. RESULTS: During a median follow-up of 11.2 years (interquartile range 6.1-16.4 years), 1031 incident HF events (13%) occurred in the UCC-SMART cohort. In the external validation data sources, a total of 24 885 incident HF events (10%) occurred. The pooled C-statistic was .696 (95% confidence interval .674-.717), with consistent performance in subgroups by sex and type of ASCVD. Predicted risks matched observed incidence in external validation. CONCLUSIONS: The SMART2-HF model enables the prediction of incident HF in patients with ASCVD. Aligned with the guideline-recommended SMART2 model for recurrent CV risk, SMART2-HF can be used as a complementary tool in this population.

Humans↗

A polygenic risk score for peripheral artery disease and major adverse limb events.

BACKGROUND AND AIMS: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. METHODS: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. RESULTS: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 [95% confidence interval 1.12-1.18], P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 [1.19-1.42], P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). CONCLUSIONS: In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.

Humans↗

Effect of revascularization on mortality associated with an elevated white blood cell count in acute coronary syndromes.

Inflammation is increasingly recognized as having an important role in patients with acute coronary syndromes. We sought to determine whether an elevated white blood cell (WBC) count would predict subsequent mortality and whether revascularization would have a protective effect. We analyzed data from 10,480 patients with acute coronary syndromes enrolled in the PURSUIT trial who had a WBC count measured on admission. WBC count values were stratified by quartiles, and death rates at 6 months were examined in univariate and multivariate analyses. Propensity analysis was performed to assess the effect of revascularization on the relation between WBC count and mortality. In the lowest quartile of WBC count, mortality was 4.0%; it was 5.8% in the second quartile, 6.7% in the third quartile, and 8.0% in the fourth quartile (p <0.001). In a multivariable model incorporating baseline demographic and clinical variables, an increasing WBC count was a significant predictor of death, with a hazard ratio of 1.07 per 1,000/microl increment in WBC count (p <0.001). Furthermore, the interaction term between mortality due to an elevated WBC count and benefit of in-hospital revascularization was significant (hazard ratio 0.94, p = 0.032), suggesting that the excess risk due to an elevated WBC count was attenuated by revascularization. An elevated WBC count at hospital admission, although only a crude index of inflammation, nevertheless is an independent predictor of death at 6 months in patients with acute coronary syndromes. This finding supports a pivotal role for inflammation in acute coronary syndromes. Importantly, this study suggests that in-hospital revascularization may mitigate some of the excess risk due to inflammation.

Acute Disease↗

Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study.

Platelet adhesion, activation, and aggregation are central to thrombus formation, which follows atherosclerotic plaque disruption and causes acute coronary syndromes. Aspirin and clopidogrel exert their antiplatelet effects by inhibiting thromboxane A2 production and adenosine diphosphate-induced platelet aggregation pathways, respectively. Aspirin has proven benefits in primary and secondary prevention of coronary artery disease. Clopidogrel, an alternative antiplatelet agent used in patients with aspirin intolerance, is especially useful in combination with aspirin after coronary stent procedures. The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study demonstrates for the first time the benefit of adding clopidogrel to aspirin rather than using aspirin alone in patients having acute coronary syndromes without ST-segment elevation myocardial infarction. Patients who are resistant to aspirin (up to 10%) have higher rates of cardiovascular events and may derive special benefit from the combination therapy. Aspirin resistance can be assessed through platelet aggregometry testing, measurement of urinary thromboxane metabolites, and, possibly, genomic testing in the future.

Acute Disease↗

Relation of inflammation and benefit of statins after percutaneous coronary interventions.

BACKGROUND: Beyond lipid lowering, statins are known to possess antiinflammatory and antithrombotic properties. Recent studies suggested an association between statins and early reduction in death or myocardial infarction (MI) after percutaneous coronary interventions (PCIs). We sought to examine the interrelationship between inflammation, statin use, and PCI outcomes. METHODS AND RESULTS: In the year 2000, 1552 consecutive United States residents underwent elective or urgent PCI at the Cleveland Clinic and were prospectively followed for 1 year. Preprocedural serum high-sensitivity C-reactive protein (hsCRP) levels were routinely measured. Patients who had statins initiated before the procedure (39.6%) had a lower median hsCRP level (0.40 versus 0.50 mg/dL, P=0.012) independent of the baseline cholesterol levels and had less frequent periprocedural MI (defined by CKMB > or =3x upper limit of normal, 5.7% versus 8.1%, P=0.038). At 1 year, statin pretreatment was predictive of survival predominantly among patients within the highest hsCRP quartile (mortality rate with statin pretreatment versus no pretreatment when hsCRP > or =1.11 mg/dL, 5.7% versus 14.8%, P=0.009). Using multivariate analysis, preprocedural hsCRP level remained an independent predictor for 1-year death or MI only in patients without statin therapy (hazard ratio, 1.32/quartile; P=0.001). After adjusting for the propensity of receiving statins, statin pretreatment was an independent predictor for 1-year survival within the highest hsCRP quartile (hazard ratio, 0.44; P=0.039). CONCLUSIONS: Statin therapy before PCI is associated with a marked reduction in mortality among patients with high hsCRP levels. A hsCRP-guided strategy may improve targeting of statin therapy and clinical outcome among patients undergoing PCI.

Aged↗

An invasive strategy is associated with decreased mortality in patients with unstable angina and non-ST-elevation myocardial infarction: GUSTO IIb trial.

There has been much debate concerning an invasive versus a conservative strategy for patients with acute coronary syndromes. The purpose of this study was to determine whether early in-hospital catheterization reduced mortality in patients with unstable angina and non-ST-elevation myocardial infarction. We performed a retrospective analysis of data collected in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial, which compared hirudin and heparin in patients with acute coronary syndromes. We identified 8011 patients with non-ST-segment elevation myocardial infarction and unstable angina who were enrolled in the trial. The primary endpoints were all-cause mortality at 30 days and 1 year. Data were analyzed with multivariate hazards models and propensity scores.After accounting for inception time bias, there were 7897 patients identified, of whom 4536 patients (57%) underwent invasive therapy and 3361 (43%) underwent conservative therapy. Adjusting for propensity scores, the adjusted 30-day mortality for the invasive group was 2.5% compared with 2.7% in the conservative group (P = 0.92); at 1 year, the invasive group had a 6.2% mortality, versus 8.6% in the conservative group (P = 0.005). In a multivariate analysis that adjusted for other clinical factors, an invasive strategy was associated with lower 1-year mortality (hazard ratio = 0.46; 95% confidence interval: 0.10 to 0.84). In patients presenting with acute coronary syndromes, an invasive strategy is associated with improved survival at 1 year even after adjusting for baseline differences.

Aged↗

Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: results of the Coronary Revascularization Using Integrilin and Single bolus Enoxaparin Study.

OBJECTIVES: This study was designed to assess whether use of enoxaparin during percutaneous coronary intervention (PCI) increased bleeding compared with unfractionated heparin, in addition to background therapy with eptifibatide. BACKGROUND: Data supporting the benefits of enoxaparin and the glycoprotein IIb/IIIa inhibitor eptifibatide evolved in parallel. Information on combining these two classes of medications is limited. METHODS: A total of 261 patients undergoing elective or urgent PCI were randomized to either eptifibatide plus enoxaparin or eptifibatide plus unfractionated heparin. RESULTS: The primary end point of the study, the bleeding index (change in hemoglobin corrected for blood transfusions), was 0.8 in the patients randomized to enoxaparin and 1.1 in patients randomized to unfractionated heparin (p = 0.15). The rate of vascular access site complications was 9.3% in the enoxaparin arm versus 9.8% in the unfractionated heparin arm (p = NS). The rate of bleeding complications was not significantly different between the two arms of the study, including in those patients who received vascular closure devices. The rate of angiographic complications was 6.3% in the enoxaparin group and 6.2% in the unfractionated heparin group (p = NS). Similarly, there were no significant differences in the composite of death, myocardial infarction, or urgent target vessel revascularization at 48 h or 30 days. CONCLUSIONS: Compared with unfractionated heparin plus eptifibatide, the combination of enoxaparin plus eptifibatide is not associated with an excess of bleeding or vascular complications, including in those receiving closure devices. Despite no monitoring of anticoagulation activity with enoxaparin, there was no apparent increase in angiographic or clinical complications.

Adult↗

Carotid brachytherapy for in-stent restenosis.

Carotid stenting has emerged as an alternative revascularization modality to endarterectomy for the treatment of carotid artery disease. Restenosis of a carotid stent may be occasionally seen. Our experience in intravascular radiation therapy for coronary restenosis has provided us the opportunity to explore this treatment strategy for carotid restenosis. We report our initial experience with brachytherapy for the treatment of restenosis after carotid stenting.

Adult↗

Scientific and therapeutic advances in antiplatelet therapy.

Over the past decade, the platelet has emerged as a pivotal entity in cardiovascular diseases. Indeed, the 'preeminence of the platelet' has spawned a variety of drugs that have been shown in large-scale randomized trials to improve patient outcomes in acute coronary syndromes and percutaneous revascularization procedures. Although the platelet was initially viewed only as a bystander in haemostasis, it is now evident that the platelet is in fact a key mediator of thrombosis as well as of inflammation. New insights at the cellular and genomic levels will probably generate novel drugs to inhibit platelet function more effectively and safely than previously possible.

Adenosine Diphosphate↗

The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study: to what extent should the results be generalizable?

The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study investigated the use of clopidogrel in the treatment of acute coronary syndromes. Clopidogrel treatment led to an impressive 20% relative risk reduction in the composite outcome measure of vascular death, myocardial infarction, and stroke. Increased bleeding and greater requirements for blood transfusions were seen with clopidogrel. The addition of clopidogrel to aspirin represents a major advance in the treatment of acute coronary syndromes.

Angina, Unstable↗

Using C-reactive protein to assess cardiovascular disease risk.

C-reactive protein (CRP), a marker of inflammation, is directly involved in atherogenesis, and elevated CRP levels (as measured by highly sensitive assays) are associated with increased cardiovascular risk. We welcome the recent joint guidelines on CRP testing from the Centers for Disease Control and Prevention and the American Heart Association; however, whereas the guidelines suggest measuring the CRP level only in patients at intermediate risk, we advocate measuring it as well in patients at high risk.

Biomarkers↗

Superficial femoral artery occlusion: nitinol stents achieve better flow and reduce the need for medications than balloon angioplasty alone.

BACKGROUND: Nitinol slotted tube stents are of great potential benefit in superficial femoral artery (SFA) interventions due to their elastic properties. However, a paucity of data exists for their efficacy in total SFA occlusions. METHODS: Using the Cleveland Clinic Foundation Peripheral Database, we identified 40 consecutive patients who underwent percutaneous revascularization for chronically occluded SFA and addressed the outcome stratifying for stent use. We evaluated the reduction in the pressure gradient across the lesion and the need for medication following revascularization. RESULTS: Of the 40 patients, twenty-six underwent balloon angioplasty alone and 14 received nitinol slotted tube stents. Patients were well matched for age and cardiovascular risk factors. Similarly, there were no differences in baseline ankle brachial index (ABI) or claudication class between the groups. Compared to angioplasty alone, stenting was associated with a greater reduction in translesional pressure gradient (72 mmHg versus 32 mmHg; p = 0.002). In addition, patients treated with stents were less likely to require post-procedure adjunctive medical treatment (7.1% versus 42.6%; p = 0.03). CONCLUSION: In SFA occlusion, stenting results in greater reduction in translesional pressure gradient and reduced need for adjunctive medical treatment.

Aged↗