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Biomedical subjects

Joshua A Beckman

Publications and source records attributed to Joshua A Beckman.

At least 19 recordsLinked to original sources

ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for noncardiac surgery: focused update on perioperative beta-blocker therapy--a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery).

The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines makes every effort to avoid any actual, potential, or perceived conflict of interest that might arise as a result of an industry relationship or personal interest of the writing committee. Specifically, all members of the writing committee, as well as peer reviewers of the document, were asked to provide disclosure statements of all such relationships that might be perceived as real or potential conflicts of interest. These statements are reviewed by the parent task force, reported orally to all members of the writing committee at each meeting, and updated and reviewed by the writing committee as changes occur. Please see Appendix 1 for author relationships with industry and Appendix 2 for peer reviewer relationships with industry. These guidelines attempt to define practices that meet the needs of most patients in most circumstances. These guideline recommendations reflect a consensus of expert opinion after a thorough review of the available, current scientific evidence and are intended to improve patient care. If these guidelines are used as the basis for regulatory/payer decisions, the ultimate goal is quality of care and serving the patient's best interests. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and patient in light of all the circumstances presented by that patient.

Adrenergic beta-Antagonists↗

The United States preventive services task force recommendation statement on screening for peripheral arterial disease: more harm than benefit?

Under the auspices of the Agency for Healthcare Research and Quality, the United States Preventive Services Task Force (USPSTF) recently released an update to its 1996 Peripheral Arterial Disease (PAD) Screening Recommendation Statement. The USPSTF recommended against PAD screening, giving the practice a "D" level recommendation. This level suggests that little or no benefit could accrue from PAD screening and that screening-associated harm could occur. The present commentary disputes the Task Force's recommendation. The USPSTF statement omitted important peer-reviewed data on the prevalence, screening efficacy, and short-term adverse prognosis of patients with PAD and failed to consider the beneficial outcomes that probably would result from timely diagnosis and treatment of this important manifestation of atherosclerosis. The Task Force implied that screening may lead to unnecessary tests, including increased risk associated with use of contrast angiographic studies. However, most patients with PAD have neither classic symptoms of leg claudication nor threatened limbs but have an extraordinarily high rate of adverse cardiovascular events, such as myocardial infarction, stroke, and death--events that should serve as a key rationale for screening. Medical therapy, including risk factor modification and antiplatelet medications, is known to reduce cardiovascular morbidity and mortality rates in these patients. The Task Force's recommendation against PAD detection may itself adversely result in inadequate recognition and treatment of PAD, with adverse public health consequences. We encourage the USPSTF to reevaluate the extant data, add vascular specialty expertise to its review group, and reconsider its recommendation.

Arterial Occlusive Diseases↗

Advanced glycation end products: sparking the development of diabetic vascular injury.

Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-kappaB and its target genes. Soluble AGEs activate monocytes, and AGEs in the basement membrane inhibit monocyte migration. AGE-bound RAGE increases endothelial permeability to macromolecules. AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species. Because of the emerging evidence about the adverse effects of AGEs on the vasculature of patients with diabetes, a number of different therapies to inhibit AGEs are under investigation.

Animals↗

Family history of diabetes is a major determinant of endothelial function.

OBJECTIVES: We evaluated whether endothelial dysfunction was present in nondiabetic persons with a family history (FH) of diabetes and assessed its relationship with insulin resistance and atherosclerosis risk factors. BACKGROUND: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. METHODS: Oral glucose tolerance and brachial artery flow-mediated, endothelium-dependent vasodilation (EDV) were assessed in 38 nondiabetic subjects; offspring of two parents with T2D (FH+) or with no first-degree relative with diabetes (FH-). RESULTS: Although fasting glucose was higher in FH+ than FH- (5.3 +/- 0.1 mmol/l vs. 4.9 +/- 0.1 mmol/l, p < 0.03), glycemic burden assessed as 2-h or area-under-the-curve glucose after glucose load or glycosylated hemoglobin (HbA1c), and measures of insulin sensitivity or inflammation did not differ. Brachial artery flow-mediated EDV was reduced in FH+ (7.1 +/- 0.9% vs. 11.7 +/- 1.6%, p < 0.02), with no difference in nitroglycerin-induced endothelium-independent vasodilatation. In the combined cohort, only FH+ (r2 = 0.12, p < 0.02) and HbA1c (r2 = 0.14, p < 0.02) correlated with EDV. Insulin resistance, assessed by tertile of homeostasis model assessment of insulin resistance (HOMA-IR), was associated with impaired endothelium-dependent vasodilatation in FH- (p < 0.03, analysis of variance), but not in FH+, as even the most insulin-sensitive FH+ offspring had diminished endothelial function. In multiple regression analysis, including established cardiac risk factors, blood pressure and lipids, HbA1c, and HOMA-IR, FH remained a significant determinant of EDV (p = 0.04). CONCLUSIONS: Bioavailability of nitric oxide is lower in persons with a strong FH of T2D. Glycemic burden, even in the nondiabetic range, can contribute to endothelial dysfunction. Abnormalities of endothelial function may contribute to atherosclerosis before development of overt diabetes.

Adult↗

The nonlipid effects of statins on endothelial function.

Hydroxymethylglutaryl-coenzyme A reductase inhibitors or statins constitute one of the wonder drugs of the last 2 decades. Use of this hypolipidemic medication class reduces morbidity and mortality in patients with a wide variety of cholesterol levels. Beneficial effects of the medication are seen in advance of changes in lipids suggesting nonlipid mechanisms may play a role in mediating these benefits of statins. One important nonlipid mechanism by which statins may improve vascular outcomes is restoration of normal endothelial cell function. This review will discuss the nonlipid effects of statins on endothelial cell function to highlight other avenues of benefit conferred by these medications.

Cholesterol, LDL↗

Automated oscillometric determination of the ankle-brachial index provides accuracy necessary for office practice.

Peripheral arterial disease (PAD) remains underdiagnosed by primary care and cardiovascular physicians. The office-based assessment of PAD is limited by the need for specialized equipment and the time required for performance of the ankle-brachial index (ABI). We explored whether the accuracy of automated ABI measurement by oscillometry compared favorably with the gold-standard method using continuous-wave Doppler ultrasound. Consecutive patients referred to our university hospital noninvasive vascular laboratory for ABI measurement were invited for participation. Of 205 patients, 201 participated, including 55 with PAD. The ABI was measured by automated oscillometry and Doppler ultrasound. The test of trends revealed a correlation coefficient of 0.78 in the left leg and 0.78 in the right leg (P<0.01 for both). The mean ABI difference between methods was 0.04+/-0.01 and 0.06+/-0.01, respectively, in the left and right legs. The differences between the methods followed a normal distribution. Oscillometric determination of the ABI provides an accurate determination of the ABI in an outpatient population. Our findings show automated oscillometry to be a reliable and easier method of ABI measurement, lowering the barrier to incorporation of this diagnostic test into clinical practice.

Aged↗

Comparison of usefulness of inflammatory markers in patients with versus without peripheral arterial disease in predicting adverse cardiovascular outcomes (myocardial infarction, stroke, and death).

We tested the hypothesis that a combination of measurements of different aspects of atherosclerosis, including burden of atherosclerosis and levels of inflammation, would contain more predictive information than either alone in an outpatient population. We enrolled 110 patients (62 +/- 15 years of age) who were referred to the noninvasive vascular laboratory for sequential Doppler pressure measurements of the lower extremities. We measured ankle-brachial index (ABI) and serum markers of inflammation and followed subjects for a mean of 2.25 years. Fifty subjects did not have peripheral arterial disease (PAD; ABI > or =0.9), whereas 60 did (ABI <0.9). Markers of inflammation, including C-reactive protein (3.83 +/- 0.9 vs 2.11 +/- 1.1, p = 0.019), were higher in subjects who had PAD. During follow-up, 42% developed an event (myocardial infarction, stroke, unplanned coronary or lower extremity revascularization, or death). Decreasing ABI (chi-square 7.3, p = 0.026) and increasing C-reactive protein (chi-square 22.1, p <0.001) increased the risk of an event. Risk increased sixfold between the lowest and highest groups for all events and fourfold for hard events (myocardial infarction, stroke, and death) using both C-reactive protein and ABI. In conclusion, patients who have PAD and increased inflammation are at highest risk for adverse cardiovascular outcomes. Characterizing atherosclerosis on the basis of these parameters provides important prognostic information.

Adult↗

Abnormal cytology predicts poor prognosis in cancer patients with pericardial effusion.

PURPOSE: Pericardial tamponade is a life-threatening disorder caused by varying medical conditions. Malignancy and complications of its treatment are a common cause of pericardial effusion. The natural history of pericardial effusion remains largely unknown. We investigated the association of malignancy with adverse outcomes after pericardiocentesis. PATIENTS AND METHODS: Consecutive patients undergoing pericardiocentesis at a single institution between January 1, 1999, and January 31, 2003, were included. Death was confirmed with the Social Security Death Index. Survival estimates were obtained by the Kaplan-Meier method. Cox regression was performed to determine the clinical characteristics associated with death. RESULTS: Two hundred nineteen patients underwent pericardiocentesis during the study period. The effusion was cancer-related in 43.8% of cases. Median survival was 59.6 weeks (95% CI, 24.3 to 94.8 weeks). During the follow-up period, 47.9% of patients died. Cancer-related pericardial effusion was associated with decreased survival (median, 15.1 weeks). Abnormal fluid cytology was further associated with poor prognosis among patients with malignancy (median survival, 7.3 v 29.7 weeks; P = .022). Patients with cancer-related pericardial effusion were more likely to require repeat pericardiocentesis (OR = 6.0; P = .001) and pericardial surgery (odds ratio [OR] OR = 5.7; P < .001). Cancer-related effusion and abnormal cytology were independent predictors of death in a multivariate model. CONCLUSION: Malignancy is the most common cause of pericardial effusion in a tertiary care center. Cancer-related pericardial effusion is associated with adverse outcomes, and abnormal cytology further worsens prognosis. The poor survival among cancer patients with pericardial effusion and abnormal fluid cytology may have important implications for management.

Adult↗

International normalized ratio increase before warfarin-associated hemorrhage: brief and subtle.

OBJECTIVE: To determine the relationship between serial international normalized ratios (INRs) in patients who have been undergoing long-term anticoagulation and the onset of warfarin-associated bleeding complications. METHODS: The study cohort consisted of 2391 patients treated in the Anticoagulation Service at Brigham and Women's Hospital, Boston, Mass, from April 1999 through July 2003. For each patient with a bleeding event, we selected 2 controls who were matched for age, sex, indication for warfarin therapy, and duration of enrollment in our Anticoagulation Service. RESULTS: Warfarin-related hemorrhage occurred in 32 patients (1.3%). The mean +/- SD INRs at the time of the bleeding event or matched patient's event date (5.9 +/- 5.9 vs 2.3 +/- 0.7; P<.001) and the mean+/-SD last INRs before the bleeding event or matched patient's event date (3.0 +/- 1.2 vs 2.1 +/- 0.8; P<.001) were higher in the patients than in the controls. The last INRs before the bleeding event were obtained an average of 11.6 +/- 17.8 (mean +/- SD) days before the event in the patients and 18.3 +/- 28.0 (mean +/- SD) days before the matched date in the controls (P = .22). The mean second-to-last INRs were similar in both groups (2.8 +/- 2.1 vs 2.3 +/- 0.8; P = .11). When the INRs were plotted in relation to the time before the onset of bleeding, a marked increase in the patients' INRs was observed shortly before the bleeding began. CONCLUSIONS: Serial INRs are poor predictors of hemorrhagic events. There appears to be only a brief warning period during which a slightly elevated INR predicts an imminent bleeding event.

Adult↗

Atorvastatin restores endothelial function in normocholesterolemic smokers independent of changes in low-density lipoprotein.

Cigarette smoking impairs endothelial function. Hydroxymethylglutaryl (HMG) CoA reductase inhibitors (statins) may favorably affect endothelial function via nonlipid mechanisms. We tested the hypothesis that statins would improve endothelial function independent of changes in lipids in cigarette smokers. Twenty normocholesterolemic cigarette smokers and 20 matched healthy control subjects were randomized to atorvastatin 40 mg daily or placebo for 4 weeks, washed out for 4 weeks, and then crossed-over to the other treatment. Baseline low-density lipoprotein (LDL) levels were similar in smokers and healthy subjects, 103+/-22 versus 95+/-27 mg/dL, respectively (P=NS) and were reduced similarly in smokers and control subjects by atorvastatin, to 55+/-30 and 58+/-20 mg/dL, respectively (P=NS). Vascular ultrasonography was used to determine brachial artery, flow-mediated, endothelium-dependent, and nitroglycerin-mediated, endothelium-independent vasodilation. To elucidate potential molecular mechanisms that may account for changes in endothelial function, skin biopsy specimens were assayed for eNOS mRNA, eNOS activity, and nitrotyrosine. Endothelium-dependent vasodilation was less in smokers than nonsmoking control subjects during placebo treatment, 8.0+/-0.6% versus 12.1+/-1.1%, (P=0.003). Atorvastatin increased endothelium-dependent vasodilation in smokers to 10.5+/-1.3% (P=0.017 versus placebo) but did not change endothelium-dependent vasodilation in control subjects (to 11.0+/-0.8%, P=NS). Endothelium-independent vasodilation did not differ between groups during placebo treatment and was not significantly affected by atorvastatin. Multivariate analysis did not demonstrate any association between baseline lipid levels or the change in lipid levels and endothelium-dependent vasodilation. Cutaneous nitrotyrosine levels and skin microvessel eNOS mRNA, but not ENOS activity, were increased in smokers compared with controls but unaffected by atorvastatin treatment. Atorvastatin restores endothelium-dependent vasodilation in normocholesterolemic cigarette smokers independent of changes in lipids. These results are consistent with a lipid-independent vascular benefit of statins but could not be explained by changes in eNOS message and tissue oxidative stress. These findings implicate a potential role for statin therapy to restore endothelial function and thereby investigate vascular disease in cigarette smokers.

Adult↗

The top 12 advances in vascular medicine.

In the past decade, impressive strides have been made in the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic diseases, thanks in large part to the explosive growth in both vascular biology and clinical vascular medicine. We review what we consider to be the top 12 advances in this field: the discovery of nitric oxide, the metabolic syndrome, new thrombophilic disorders, therapeutic angiogenesis, endoluminal treatment of chronic venous disease, and a variety of drugs, including sildenafil, cilostazol, low-molecular-weight heparins, oral direct thrombin inhibitors, clopidogrel, statins, and angiotensin-converting enzyme inhibitors and angiotensin-receptor blocking agents.

Angiotensin-Converting Enzyme Inhibitors↗

Branch vessel complications are increased in aortic dissection patients with renal insufficiency.

Morbidity and mortality from aortic dissection remain high despite advances in diagnosis and treatment. Simple markers to identify patients at high risk for non-aortic complications of dissection are lacking. We investigated the effect of renal insufficiency on the presentation, complications, and outcome of patients with acute aortic dissection. We evaluated 638 patients with type A and 365 patients with type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 2000. Chi-squared and Student's ttesting were performed to identify the effect of renal insufficiency on patient presentation, management, and outcome. Patients with renal insufficiency more often required nitroprusside for blood pressure control (type A: 40.7% vs 31.1%, p = 0.049; type B: 66.7% vs 37.3, p = 0.0001) and had a greater risk of mesenteric ischemia (type A: 10.7% vs 1.4%, p < 0.0001; type B: 17.7% vs 3.0%, p < 0.0001). In conclusion, aortic dissection patients with renal insufficiency are at increased risk for drug-resistant hypertension and aortic branch vessel compromise. Routine measurement of serum creatinine provides a readily accessible clinical marker for important complications. Upon recognition, renal impairment indicates a need for close monitoring, aggressive blood pressure control, and evaluation of aortic branch vessel circulations.

Acute Disease↗