Faculty Bibliography
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Diabetes mellitus is a coronary heart disease risk equivalent for peripheral vascular disease
Diabetes mellitus (diabetes) is associated with significantly increased risk of peripheral vascular disease. Diabetes is classified as a coronary heart disease (CHD) risk equivalent, but it is unknown whether diabetes is a CHD risk equivalent for peripheral vascular disease. The objective was to evaluate the odds of peripheral arterial disease (PAD) or carotid artery stenosis (CAS) among participants with diabetes, CHD, or both, compared with participants without diabetes or CHD, in a nationwide vascular screening database. We hypothesized that diabetes and CHD would confer similar odds of PAD and CAS. METHODS: A cross-sectional analysis of all eligible Life Line Screening Inc participants age 30 to 90 years with ankle brachial indices for PAD (ankle brachial index <0.9 in either leg) and carotid artery duplex ultrasonographic imaging for CAS (internal CAS >/=50%) was performed (N=3,522,890). RESULTS: Diabetes and CHD were present in 372,330 (10.7%) and 182,760 (5.8%) of participants, respectively; PAD and CAS were present in 155,000 (4.4%) and 130,347 (3.7%) of participants. After multivariable adjustment, PAD odds were 1.56 (95% CI 1.54-1.59) and 1.69 (95% CI 1.65-1.73) for participants with diabetes or CHD, respectively. Participants with both diabetes and CHD had 2.75-fold increased odds of PAD (95% CI 2.66-2.85). Findings were similar for CAS; compared with no diabetes or CHD, CAS odds increased for participants with diabetes alone (1.53, 95% CI 1.50-1.56), CHD alone (1.72, 95% CI 1.68-1.76), and both diabetes and CHD (2.57, 95% CI 2.49-2.66). Findings were consistent for women and men. CONCLUSION: In a large database of more than 3.5 million self-referred participants, diabetes was a CHD risk equivalent for PAD and CAS, and participants with comorbid diabetes and CHD had an especially robust association with PAD and CAS. Counseling regarding screening and prevention of peripheral vascular disease may be useful for patients with diabetes.
PMCID:5325078
PMID: 28224925
ISSN: 1097-6744
CID: 2455482
Arteriosclerosis, thrombosis, & vascular biology. 2017:37(4):707-716.DOI: 10.1161/ATVBAHA.116.308126
Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1beta Pathway in Systemic Lupus Erythematosus
OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with the premature development of cardiovascular disease. The platelet-endothelium interaction is important in the pathogenesis of cardiovascular disease. In this study, we investigated the platelet phenotype from patients with SLE and matched controls, and their effect on endothelial cells. APPROACH AND RESULTS: Platelet aggregability was measured in 54 SLE subjects off antiplatelet therapy (mean age 40.1+/-12.8 years; 82% female; 37% white) with age- and sex-matched controls. Platelets were coincubated with human umbilical vein endothelial cells (HUVECs) and changes to gene expression assessed by an RNA array and quantitative reverse transcription polymerase chain reaction. SLE disease activity index ranged from 0 to 22 (mean 5.1+/-3.9). Compared with controls, patients with SLE had significantly increased monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation. An agnostic microarray of HUVECs cocultured with SLE platelets found a platelet-mediated effect on endothelial gene pathways involved in cell activation. Sera from SLE versus control subjects significantly increased (1) activation of control platelets; (2) platelet adhesion to HUVECs; (3) platelet-induced HUVEC gene expression of interleukin-8, and ICAM-1; and (4) proinflammatory gene expression in HUVECs, mediated by interleukin-1beta-dependent pathway. Incubation of SLE-activated platelets with an interleukin-1beta-neutralizing antibody or HUVECs pretreated with interleukin-1 receptor antibodies attenuated the platelet-mediated activation of endothelial cells. CONCLUSIONS: Platelet activity measurements and subsequent interleukin-1beta-dependent activation of the endothelium are increased in subjects with SLE. Platelet-endothelial interactions may play a role in the pathogenesis of cardiovascular disease in patients with SLE.
PMCID:5597960
PMID: 28153882
ISSN: 1524-4636
CID: 2437182
Perioperative Major Adverse Cardiovascular and Cerebrovascular Events Associated With Noncardiac Surgery
Importance: Major adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery. Objective: To evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions. Design, Setting, Participants: Patients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample. Main Outcomes and Measures: Perioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time. Results: Among 10581621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5975798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (P for trend <.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (P for trend <.001; aOR 1.79; CI 1.73-1.86). Conclusions and Relevance: Perioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.
PMCID:5563847
PMID: 28030663
ISSN: 2380-6591
CID: 2383672
Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease
Background Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. Methods In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. Results The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). Conclusions In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).
PMID: 27959717
ISSN: 1533-4406
CID: 2363402
Ticagrelor Compared With Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease
BACKGROUND: -In patients with symptomatic peripheral artery disease (PAD) with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. METHODS: -The Examining Use of tiCagreLor In paD (EUCLID) trial randomized 13,885 patients with PAD to treatment with ticagrelor 90mg twice daily or clopidogrel 75mg daily. Patients were enrolled based on an abnormal ankle-brachial index (ABI)
PMID: 27840336
ISSN: 1524-4539
CID: 2310872
Novel association between bone mineral density scores and the prevalence of peripheral artery disease in both sexes
The purpose of the current study was to investigate the association between bone mineral density (BMD) scores and the prevalence of peripheral artery disease (PAD) in a large cohort of subjects who underwent arterial Doppler assessments and calcaneal bone densitometry. The study was performed using data obtained from Life Line Screening Inc. Subjects were self-selected and paid for screening tests. The prevalence of PAD was significantly higher in men with osteopenia (4.5%) and osteoporosis (10.9%) compared to men with normal BMD (3.0%) (p<0.001). Osteopenia (odds ratio (OR) 1.3) and osteoporosis (OR 2.3) were found to be independent risk factors for the presence of PAD in men. The prevalence of PAD was significantly higher in women with osteopenia (4.8%) and osteoporosis (11.8%) compared to women with normal BMD (3.3%) (p<0.001). Osteopenia (OR 1.15) and osteoporosis (OR 1.8) were found to be independent risk factors for the presence of PAD in women. The current study reports a strong association of abnormal BMD analysis with the prevalence of PAD, which persists even when controlling for age and associated atherosclerotic risk factors. Although the mechanism by which these two disease processes is related is not completely elucidated, the presence of osteoporosis should make clinicians aware of the possibility of occult PAD or associated atherosclerotic disease in appropriate patients.
PMID: 27799423
ISSN: 1477-0377
CID: 2297162
Increased Prevalence of Moderate and Severe PAD in the Native American/Alaskan Native Population; a study of 96,000 NA/AN
OBJECTIVE: Peripheral arterial disease (PAD) disproportionally affects racial groups in the United States. Few studies have analyzed the rates of PAD in the American Indian (AI)/ Alaskan Native (AN) population. In this paper we compare the prevalence of PAD in the AI/AN as compared to white and non-white Americans. METHODS: The study data were provided by Life Line Screening (Independence, Ohio). The cohort consists of self-referred individuals who paid for vascular screening tests. Mild to moderate and severe PAD were defined as having an ankle brachial index (ABI) in at least one extremity of < .9 and <.5 respectively. Univariate and multivariate analysis were performed to compare the rates of PAD between AI/AN, Caucasians, and non-whites. RESULTS: The original sample for which this study was obtained included 3,444,272 people. Of this group there was a predominance of females 64.5% (2,221,555) compared to 35.5% (1,222,716) males. The Native American/ Alaskan Native population was 2.8% of the sample (96,440). In our univariate analysis AI/AN had the highest rates of mild-moderate and severe PAD when compared to whites (OR 1.78 and 2.14 respectively) and non-whites (OR 1.52 and 1.82 respectively). We then controlled for atherosclerotic risk factors in our multivariate analysis and the AI/NA cohort had persistently higher rates of both moderate and severe PAD compared to whites (OR 1.32 and 1.40) but not compared to non-whites (OR .95 and .92). CONCLUSIONS: Here we present the largest epidemiology study of PAD in AI/NA to date. AI/NA people have disproportionately high rates of both mild-to moderate and severe PAD when compared to whites and non-white Americans. After controlling for atherosclerotic risk factors the rates of PAD remain high for AI/NA when compared to whites but not when compared to non-whites. While it is possible that a combination of diet and lifestyle choices are responsible for the high rates of PAD in this population, genetic factors may be involved as well, and deserve further investigation. Optimal medical management may help to prevent the complications of PAD in this patient population.
PMID: 27554686
ISSN: 1615-5947
CID: 2221502
ASSOCIATION BETWEEN SEX AND VASCULAR DISEASE IN DIFFERENT ARTERIAL BEDS: A POPULATION DATABASE OF OVER 3.6 MILLION PEOPLE [Meeting Abstract]
ISI:000375188703125
ISSN: 0735-1097
CID: 2962412
RNASEQ IDENTIFIES DIFFERENTIAL EXPRESSION OF PLATELET TRANSCRIPTS IN SUBJECTS WITH PERIPHERAL ARTERY DISEASE [Meeting Abstract]
ISI:000375188703085
ISSN: 0735-1097
CID: 2962392
DIABETES MELLITUS IS A CARDIOVASCULAR DISEASE (CVD) RISK EQUIVALENT FOR PERIPHERAL ARTERIAL DISEASE AND CAROTID ARTERY STENOSIS [Meeting Abstract]
ISI:000375188703126
ISSN: 0735-1097
CID: 2962402
