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Association between Advanced Age and Vascular Disease in Different Arterial Territories: A Population Database of Over 3.6 Million Subjects
Savji, Nazir; Rockman, Caron B; Skolnick, Adam; Guo, Yu; Adelman, Mark A; Riles, Thomas; Berger, Jeffrey S
OBJECTIVE: This study sought to determine the relationship between vascular disease in different arterial territories and advanced age. BACKGROUND: Vascular disease in the peripheral circulation is associated with significant morbidity and mortality. There is little data to assess the prevalence of different phenotypes of vascular disease in the very elderly. METHODS: Over 3.6 million self-referred participants from 2003-2008 who completed a medical and lifestyle questionnaire in the United States were evaluated by screening ankle brachial indices <0.9 for peripheral artery disease (PAD), and ultrasound imaging for carotid artery stenosis (CAS) >50% and abdominal aortic aneurysm (AAA) >3cm. Participants were stratified by decade of life. Multivariate logistic regression analysis was used to estimate odds of disease in different age categories. RESULTS: Overall, the prevalence of PAD, CAS, and AAA, was 3.7%, 3.9%, and 0.9%, respectively. Prevalence of any vascular disease increased with age (40-50y: 2%; 51-60y: 3.5%; 61-70y: 7.1%; 71-80y: 13.0%; 81-90y: 22.3%; 91-100y: 32.5%; P<0.0001). Prevalence of disease in each vascular territory increased with age. After adjustment for sex, race/ethnicity, body mass index, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterolemia, and exercise, the odds of PAD (OR 2.14, 95% CI 2.12-2.15), CAS (OR 1.80, 95% CI 1.79-1.81), and AAA (OR 2.33, 95% CI 2.30-2.36]) increased with every decade of life. CONCLUSION: There is a dramatic increase in the prevalence of PAD, CAS, and AAA with advanced age. More than 20% and 30% of octo- and nonagenarians, respectively, have vascular disease in at least 1 arterial territory.
PMID: 23500290
ISSN: 0735-1097
CID: 248012
Thrombotic and bleeding complications after orthopedic surgery
Oberweis, Brandon S; Nukala, Swetha; Rosenberg, Andrew; Guo, Yu; Stuchin, Steven; Radford, Martha J; Berger, Jeffrey S
BACKGROUND: Thrombotic and bleeding complications are major concerns during orthopedic surgery. Given the frequency of orthopedic surgical procedures and the limited data in the literature, we sought to investigate the incidence and risk factors for thrombotic (myocardial necrosis and infarction) and bleeding events in patients undergoing orthopedic surgery. METHODS AND RESULTS: We performed a retrospective cohort analysis of 3,082 consecutive subjects >/=21 years of age undergoing hip, knee, or spine surgery between November 1, 2008, and December 31, 2009. Patient characteristics were ascertained using International Classification of Diseases, Ninth Revision, diagnosis coding and retrospective review of medical records, and laboratory/blood bank databases. In-hospital outcomes included myocardial necrosis (elevated troponin), major bleeding, coded myocardial infarction, and coded hemorrhage as defined by International Classification of Diseases, Ninth Revision, coding. Of the 3,082 subjects, mean age was 60.8 +/- 13.3 years, and 59% were female. Myocardial necrosis, coded myocardial infarction, major bleeding, and coded hemorrhage occurred in 179 (5.8%), 20 (0.7%), 165 (5.4%), and 26 (0.8%) subjects, respectively. Increasing age (P < .001), coronary artery disease (P < .001), cancer (P = .004), and chronic kidney disease (P = .01) were independent predictors of myocardial necrosis, whereas procedure type (P < .001), cancer (P < .001), female sex (P < .001), coronary artery disease (P < .001), and chronic obstructive pulmonary disease (P = .01) were independent predictors of major bleeding. CONCLUSION: There is a delicate balance between thrombotic and bleeding events in the perioperative period after orthopedic surgery. Perioperative risk of both thrombosis and bleeding deserves careful attention in preoperative evaluation, and future prospective studies aimed at attenuating this risk are warranted.
PMCID:3595114
PMID: 23453114
ISSN: 0002-8703
CID: 231332
Statins and diabetes: the good, the bad, and the unknown
Axsom, Kelly; Berger, Jeffrey S; Schwartzbard, Arthur Z
The ability for statins to reduce major cardiovascular events and mortality has lead to this drug class being the most commonly prescribed in the world. In particular, the benefit of these drugs in type 2 diabetes (T2D) is well established. In February 2012, the Food and Drug Administration released changes to statin safety label to include that statins have been associated with increases in hemoglobin A1C and fasting serum glucose levels. This has stirred much debate in the medical community. Estimate for new onset diabetes from statin treatment is approximately one in 255 patients over four years. The number needed to treat for statin benefit is estimated at one in 40 depending on the population. The mechanism of this link remains unknown. Statins may accelerate progression to diabetes via molecular mechanisms that impact insulin resistance and cellular metabolism of carbohydrates. It remains clear that the benefit of statin therapy outweighs the risk of developing diabetes.
PMID: 23299640
ISSN: 1523-3804
CID: 211512
The prevalence of carotid artery stenosis varies significantly by race
Rockman, Caron B; Hoang, Han; Guo, Yu; Maldonado, Thomas S; Jacobowitz, Glenn R; Talishinskiy, Toghrul; Riles, Thomas S; Berger, Jeffrey S
OBJECTIVE: Certain races are known to be at increased risk for stroke, and the prevalence of carotid artery stenosis (CAS) is thought to vary by race. The goal of this report was to study the prevalence of CAS in different races by analyzing a population of subjects who underwent vascular screening examinations. METHODS: The study data were provided by Life Line Screening. The cohort consists of self-referred individuals who paid for vascular screening tests. Subjects <40 and >100 years of age and those who reported a prior stroke or carotid artery intervention were excluded. Of the remaining 3,291,382 subjects, 3.7% did not self-identify a race. CAS was defined as stenosis in either internal carotid artery >/=50% by duplex ultrasound velocity criteria. RESULTS: The 3,291,382 subjects available for analysis consisted of Caucasian (2,845,936 [90%]), African American (97,502 [3.1%]), Hispanic (75,240 [2.4%]), Asian (60,982 [1.9%]), and Native American (87,757 [2.8%]) individuals. The prevalence of CAS was 3.4% in females and 4.2% in males (P = .001). Controlling for gender and age, there was marked variation in the prevalence of CAS (P < .001) by race. Native American subjects had the highest prevalence of CAS across all age categories and in both sexes. Caucasian subjects had the second highest prevalence of CAS across most age decades and in both sexes. Among males, African American individuals had the lowest prevalence of CAS in nearly all age categories. In contrast to males, Asian females had the lowest prevalence of CAS compared with females of other races in most age groups. Multivariate analysis adjusting for atherosclerotic risk factors in addition to age confirmed race as a significant independent predictor of CAS. Compared with Caucasian subjects, African American (odds ratio [OR], 0.65), Asian (OR, 0.69), and Hispanic (OR, 0.74) subjects had a significantly lower risk of CAS, whereas Native American (OR, 1.3) subjects had a significantly higher risk of CAS. CONCLUSIONS: The prevalence of clinically significant CAS varies significantly by race. Native American and Caucasian individuals have the highest prevalence of CAS, whereas African American males and Asian females appear to have the lowest prevalence. This information adds evidence to the hypothesis that the increased stroke rate in African American subjects is likely not related to extracranial cerebrovascular disease. Furthermore, this is a novel report of an extremely high prevalence of CAS in the Native American population.
PMID: 23177534
ISSN: 0741-5214
CID: 213612
What should we do about Hypertriglyceridemia in Coronary Artery Disease Patients?
Singh, Amita; Schwartzbard, Arthur; Gianos, Eugenia; Berger, Jeffrey S; Weintraub, Howard
OPINION STATEMENT: Triglycerides are routinely obtained with standard lipid testing, but their role in cardiovascular risk is controversial. An excess of triglycerides is commonly encountered in patients with the metabolic syndrome or diabetes, and represents an excess burden of small, dense low-density lipoproteins (LDLs), which confers additive risk for cardiovascular disease. Current guidelines prioritize LDL targets first, but treatment of triglycerides once LDL targets are achieved bears consideration. Beyond lifestyle modification, potential pharmacologic therapies include statins, fibrates, niacin, omega-3 fatty acids and antidiabetic drugs. There are few trials to date comparing these agents directly in the management of hypertriglyceridemia, but available data seems to demonstrate that the greatest benefit of triglyceride lowering is experienced in a subgroup of patients with an atherogenic lipid profile (elevated triglycerides, low high-density lipoprotein (HDL), elevated small, dense LDL particles). Here, we discuss the current understanding of how triglyceride elevations impart cardiovascular risk, current therapies and the data supporting their use, and ongoing studies to elucidate the degree to which treatment of triglycerides modifies risk of future cardiovascular events.
PMID: 23109123
ISSN: 1092-8464
CID: 213932
Mean platelet volume and long-term mortality in patients undergoing percutaneous coronary intervention
Shah, Binita; Oberweis, Brandon; Tummala, Lakshmi; Amoroso, Nicholas S; Lobach, Iryna; Sedlis, Steven P; Grossi, Eugene; Berger, Jeffrey S
Increased platelet activity is associated with adverse cardiovascular events. The mean platelet volume (MPV) correlates with platelet activity; however, the relation between the MPV and long-term mortality in patients undergoing percutaneous coronary intervention (PCI) is not well established. Furthermore, the role of change in the MPV over time has not been previously evaluated. We evaluated the MPV at baseline, 30 days, 60 days, 90 days, 1 year, 2 years, and 3 years after the procedure in 1,512 patients who underwent PCI. The speed of change in the MPV was estimated using the slope of linear regression. Mortality was determined by query of the Social Security Death Index. During a median of 8.7 years, mortality was 49.3% after PCI. No significant difference was seen in mortality when stratified by MPV quartile (first quartile, 50.1%; second quartile, 47.7%; third quartile, 51.3%; fourth quartile, 48.3%; p = 0.74). For the 839 patients with available data to determine a change in the MPV over time after PCI, mortality was 49.1% and was significantly greater in patients with an increase (52.9%) than in those with a decrease (44.2%) or no change (49.1%) in the MPV over time (p <0.0001). In conclusion, no association was found between the baseline MPV and long-term mortality in patients undergoing PCI. However, increased mortality was found when the MPV increased over time after PCI. Monitoring the MPV after coronary revascularization might play a role in risk stratification.
PMCID:3538911
PMID: 23102880
ISSN: 0002-9149
CID: 209992
Hyperreactive platelet phenotypes: Relationship to altered serotonin transporter number, transport kinetics and intrinsic response to adrenergic co-stimulation
Berger, J S; Becker, R C; Kuhn, C; Helms, M J; Ortel, T L; Williams, R
The mechanism underlying a hyperreactive platelet phenotype remains unknown. Since serotonin has been shown to influence platelet biology and atherothrombosis, we sought to investigate the association of platelet serotonin transporter number, binding affinity, and uptake kinetics with platelet aggregation. A total of 542 healthy volunteers had light transmittance platelet aggregometry measured in response to varying concentrations of epinephrine, serotonin, epinephrine plus serotonin, ADP and collagen. Transporter-dependent serotonin uptake rate was determined (Vmax), as were serotonin transporter number (Bmax) and binding affinity (Kd) using 3H paroxetine binding in a homologous displacement assay, nonlinear regression and validated algorithms for kinetic modelling. Stimulation with submaximal (2muM) epinephrine concentration elicited a distinct, bimodal pattern of platelet aggregation in this population. In contrast, subjects exhibited minimal aggregation in response to serotonin alone. Co-stimulation with submaximal epinephrine and serotonin induced platelet aggregation to a level beyond that observed with either agonist alone and maintained a bimodal response distribution. Subjects with heightened (>60%) platelet aggregation to both epinephrine alone and epinephrine plus serotonin exhibited increased platelet serotonin uptake, and transporter number and affinity. In a population of healthy subjects, co-stimulation with submaximal concentrations of epinephrine and serotonin identifies a subset of individuals with a hyperreactive platelet aggregation profile that is associated with changes in platelet serotonin function.
PMCID:3582386
PMID: 23223800
ISSN: 0340-6245
CID: 211092
Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost-effectiveness analysis
Lala, A; Berger, J S; Sharma, G; Hochman, J S; Scott Braithwaite, R; Ladapo, J A
Summary. Background: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. Objectives: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies (empiric clopidogrel or prasugrel). Methods: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. Results: Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. Conclusions: Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.
PMID: 23137413
ISSN: 1538-7836
CID: 213942
ASSOCIATION BETWEEN DIABETES MELLITUS AND PREVALENCE OF VASCULAR DISEASE IN DIFFERENT ARTERIAL TERRITORIES [Meeting Abstract]
Shah, Binita; Rockman, Caron; Chesner, Jaclyn; Guo, Yu; Schwartzbard, Arthur; Weintraub, Howard; Adelman, Mark; Riles, Thomas; Berger, Jeffrey
ISI:000316555202254
ISSN: 0735-1097
CID: 1795282
Reproducibility, Pre-Analytical Variables and Effect of Aspirin On Soluble P Selectin and CD40 Ligand [Meeting Abstract]
Valdes, Vanessa; Nardi, Michael A.; Berger, Jeffrey S.
ISI:000314049600049
ISSN: 0006-4971
CID: 227512