Khether E. Raby’s research while affiliated with Boston Medical Center and other places

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Publications (26)


Low Plasma Ascorbic Acid Independently Predicts the Presence of an Unstable Coronary Syndrome 1
  • Article
  • Full-text available

May 1998

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27 Reads

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87 Citations

Journal of the American College of Cardiology

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John F Keaney

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Khether E Raby

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This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease. Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial. Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome. By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not. These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.

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Effect of Cholesterol Reduction on Myocardial Ischemia in Patients With Coronary Disease

January 1997

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16 Reads

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232 Citations

Circulation

Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. This study sought to determine whether cholesterol lowering also results in a reduction of myocardial ischemia during daily life. We enrolled 40 patients with proven coronary artery disease, total serum cholesterol between 191 and 327 mg/dL, and at least one episode of ST-segment depression on ambulatory ECG monitoring. Twenty patients were randomized to an American Heart Association Step 1 diet plus placebo (placebo group) and 20 to the same diet plus lovastatin (treatment group). Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4 to 6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. The treatment group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the placebo group. ST-segment depression was completely resolved in 13 of 20 patients (65%) in the treatment group versus 2 of 20 (10%) in the placebo group. The treatment group exhibited a highly significant reduction in ischemia (P < .001). By logistic regression, treatment with diet and lovastatin was an independent predictor of ischemia resolution. Cholesterol lowering with lovastatin appears to be effective in eliminating myocardial ischemia during daily life in a significant proportion of patients.



Peripheral Arterial-Vascular Disease in Women: Prevalence, Prognosis, and Treatment

February 1995

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8 Reads

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29 Citations

Cardiology

Lower extremity atherosclerosis results in significant morbidity in women, particularly in women following the menopause. Up to 25% of women aged 55 to 74 years are affected by this disease. When noninvasive testing is used to determine the prevalence of lower extremity atherosclerosis, and men in this age group are equally represented. Cigarette smoking, diabetes mellitus, and menopause are risk factors for atherosclerosis of particular interest in women. The prevalence of cigarette smoking is rising rapidly among women, and diabetes appears to be a greater risk factor for atherosclerosis in women than in men. Risk factor reduction, in addition to an exercise program, are important parts of the treatment program for stable claudication. In both men and women with more severe symptoms, an ankle/branchial index (ABI) of less than 0.3 is associated with more severe symptoms, an ankle/brachial index (ABI) of less than 0.3 is associated with a poor prognosis. Men and women fare equally well following revascularization for severe peripheral atherosclerosis. However, there are some data to suggest that women may be offered peripheral revascularization at a lower rate.



Identification and treatment of myocardial ischemia in patients undergoing peripheral vascular surgery

January 1994

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5 Reads

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19 Citations

Patients who have myocardial ischemia on preoperative Holter monitoring have a high risk of postoperative cardiac events after peripheral vascular surgery. We have previously reported that of 41 patients with preoperative ischemia whose clinicians were blinded to Holter results, 17 (42%) suffered cardiac events including three deaths and six myocardial infarctions. Using these data as historical controls, we determined whether unblinding clinicians to Holter results decreases risk. We screened 145 patients undergoing elective peripheral vascular surgery with preoperative Holter monitoring. Clinicians were notified of the Holter monitor results and treated patients perioperatively as they felt appropriate. Patients were followed to hospital discharge and a blinded expert determined the occurrence of cardiac events. Thirty-six patients had at least one episode of preoperative ischemia, and six (17%) had postoperative cardiac events, including no deaths and one myocardial infarction, a 2.5-fold reduction in risk when compared with historical controls (95% confidence interval 1.1-5). These 36 patients had up to 48 hours of postoperative Holter monitoring, and 22 had 120 minutes or less of ischemia per day with no adverse events, while 14 had more than 120 minutes of ischemia per day with six adverse events (p = .001). Compared with historical controls, patients prospectively identified with preoperative ischemia had a lower overall rate of adverse cardiac events postoperatively, with all events occurring in patients who had more than 120 minutes of postoperative ischemia per day. These data justify a randomized trial to examine the role of medical therapy in reducing postoperative ischemia and cardiac events.


Usefulness of Holter monitoring for detecting myocardial ischemia in patients with nondiagnostic exercise treadmill test

November 1993

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16 Reads

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22 Citations

The American Journal of Cardiology

To determine if Holter monitoring can predict cardiac risk in patients when the exercise test is nondiagnostic, a total of 90 eligible patients were monitored for 24 hours after their exercise test without alterations in baseline medications. Prospective follow-up was obtained and events were confirmed by investigators unaware of subjects' clinical data. Nineteen patients (21%) had a total of 71 episodes of ST depression, all of which were asymptomatic. During a mean follow-up of 719 days, there were 10 patients with adverse events: 3 with cardiac deaths, 3 with nonfatal myocardial infarctions, and 4 with admissions for unstable angina. Of the 10 adverse events, 9 occurred in the group of 19 with ST depression detected by Holter (relative risk 34, 95% confidence interval 10 to 114). The sensitivity of ST depression was 90%, the specificity 88%, the predictive positive value 47%, and the predictive negative value 99%. In a multivariate Cox proportional-hazards model that controlled for prior history of coronary artery disease, hypercholesterolemia, and all exercise test variables, the presence of ST depression detected by Holter was the only independent predictor of outcome. In patients with nondiagnostic exercise tests, ST depression detected by Holter monitoring identified those with an increased risk of adverse cardiac events. The absence of ST depression detected by Holter was a useful predictor of low risk.


Changing vasomotor responses of coronary arteries to nifedipine*1

September 1993

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11 Reads

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8 Citations

American Heart Journal

Coronary vasomotion is influenced by a variety of factors, including atherosclerosis and diurnal variations in alpha-adrenergic tone. The effect of such factors on the coronary response to vasodilator drugs is unknown. To determine whether there is a diurnal variation to the response of coronary arteries to nifedipine, and whether this response is altered by atherosclerosis, we studied 11 patients with smooth coronary arteries, six in the morning and five in the afternoon, and 12 patients with irregular coronary arteries, six in the morning and six in the afternoon. Changes in coronary blood flow and the vasomotor response of an epicardial coronary artery were measured before and after a 2 mg intracoronary infusion of nifedipine. There were no appreciable differences in epicardial vessel dilator response or coronary blood flow in the morning and afternoon among patients with smooth coronary arteries. By contrast, patients with irregular coronary arteries had a significantly diminished dilator response in the afternoon, without an appreciable change in coronary blood flow. We postulate that normal coronary arteries maintain basal tone throughout the day. By contrast, atherosclerotic coronary arteries cannot do the same, increasing tone in the morning in response to catecholamines. When catecholamine levels drop in the afternoon, basal tone decreases in atherosclerotic vessels, and the dilator response to nifedipine is blunted. This observation may have an important impact on the expected benefits and timing of vasodilator therapy in patients with coronary artery disease.


Myocardial Revascularization Before Repair of an Aortic Aneurysm

August 1993

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6 Reads

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4 Citations

Mayo Clinic Proceedings

Patients who undergo a vascular surgical procedure, particu­ larly aortic reconstruction, are known to be at increased risk for perioperative cardiac events. Patients with coronary artery disease who undergo a major vascular operation have an in-hospital mortality rate at least double that of patients without clinical evidence of coronary disease.'> The 5-year survival rate in patients with coronary artery disease and aortic aneurysms is 60 to 70%,3.4 which is much lower than the 5-year survival rate of 80 to 90% in patients who have coronary artery disease without peripheral vascular disease. Thus, the frequent coexistence of coronary and peripheral vascular disease substantially increases the morbidity and mortality both in the perioperative period and during long­ term follow-up. Current management strategies have been designed in an attempt to identify high-risk patients before vascular surgical procedures are performed and to imple­ ment interventions for decreasing the subsequent surgical risk. Stratification ofRisk.-Because patients with peripheral vascular disease are often inactive, they may not have car­ diac symptoms. One study showed that 64% of patients with no preoperative clinical indication of coronary disease had at least one severe stenosis, and 29% had triple-vessel or left main coronary artery disease.' The first attempt to stratify the risk for patients who underwent a noncardiac operation was based on data collected retrospectively by Goldman and associates," who assessed perioperative risk in 1,001 patients by multivariate analysis. On the basis of nine clinical and simple laboratory tests, they stratified patients into four groups of increasing risk. The Goldman index became widely used and accepted for assessing the risk of noncar­ diac operative procedures but was not directly applicable for assessing risk before vascular operations. For example, patients who undergo repair of an aortic aneurysm have much higher rates of cardiac events than those predicted by the Goldman index. Eagle and colleagues? proposed differ­ ent clinical criteria, which may be more applicable to the vascular patient.


New insights into the management of myocardial ischemia

December 1992

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6 Reads

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8 Citations

The American Journal of Cardiology

Episodes of ST depression are closely related to transient decreases in regional myocardial perfusion during physical or mental stress. At the onset of these events, there is transient constriction of atherosclerotic stenoses, with an increase in myocardial demand as reflected by increases in heart rate and blood pressure. Recent research has shown that normal epicardial coronary arteries respond to these provocations and to increasing blood flow with progressive vasodilation. In contrast, atherosclerotic vessels lose this ability to dilate and may show paradoxical constriction. This abnormal constriction parallels the response of the arteries to acetylcholine, which can be used to assess the ability of the coronary endothelium to regulate vasodilation. The loss of endothelium-dependent vasodilation appears to be an important functional manifestation of coronary atherosclerosis and a potential triggering mechanism for transient ischemia. Dysfunctional endothelium may also result in a procoagulant surface, with cell adherence and local thrombus formation. Restoration of normal endothelial function is likely to emerge as an important therapeutic objective in the management of myocardial ischemia and coronary atherosclerosis.


Citations (13)


... This is another indication of the link between ONFH and major adverse cardiovascular and cerebrovascular events and further supports a rationale of endothelial dysfunction as a common pathologic mechanism [7,13,23]. Surprisingly, although surgery-associated vascular injury might induce subsequent endothelial dysfunction [18,22], our study revealed that surgery of the lower extremities was not associated with an increase in major CVD. Similarly, the concern that major adverse cardiovascular and cerebrovascular events might be associated with long-term use of NSAIDs [24,27] or steroids [25,26] was not observed in our study. ...

Reference:

Cardiovascular and Cerebrovascular Events Are Associated With Nontraumatic Osteonecrosis of the Femoral Head
Correlation Between Preoperative Ischemia and Major Cardiac Events After Peripheral Vascular Surgery
  • Citing Article
  • August 1990

Survey of Anesthesiology

... Numerous studies 30 using perioperative Holter monitoring in high-cardiac-risk patients undergoing major surgery showed that silent, heart rate-related ST-segment depression is common postoperatively and is associated with in-hospital 22,31 and long-term morbidity and mortality. 32 Postoperative cardiac complications, including sudden death, 33,34 occurred after prolonged (Ͼ30 minutes, 35,36 Ͼ2 hours, 37,38 or Ͼ5 hours 39,40 ) silent ST-segment depression. These findings were further corroborated by studies that correlated continuous, online 12-lead ST-segment analysis with serial cardiac troponin measurements after major vascular surgery. ...

Identification and treatment of myocardial ischemia in patients undergoing peripheral vascular surgery
  • Citing Article
  • January 1994

... Myocardial ischemia occurs in 20% to 40% of patients; adverse events develop in Ͼ50% of patients. [17][18][19] The importance of perioperative myocardial ischemia detected by means of routine Holter monitoring has been shown, [20][21][22][23][24][25] although a recent report by Landesberg and associates indicated that during 11,132 patienthours of monitoring after surgery, 38 of 185 consecutive patients had 66 transient ischemic events, but only 12 patients (6.5%) sustained perioperative MIs. 19 In addition, Kirwin and coworkers were unable to correlate silent myocardial ischemia on preoperative continuous ambulatory cardiogram (ECG; Holter) monitoring with perioperative MIs. 26 Nonfatal and fatal MIs are the most important and specific "hard" outcomes that determine cardiac morbidity. ...

The Role of Ambulatory Monitoring in Assessing Cardiac Risk in Peripheral Vascular Surgery
  • Citing Article
  • September 1992

Cardiology Clinics

... The long-term poor control of blood pressure in hypertensive patients can increase the pressure on the arterial vessel wall, damage ECs, and easily enter the arterial wall, stimulating the proliferation of vascular smooth muscle cells (VSMCs) and causing atherosclerosis, thereby causing coronary heart disease [84,85]. However, the mechanistic link between pathological changes and the elevated blood pressure-associated pathological changes in the vessel wall remains unclear. ...

Pathophysiology of ischemia in patients with coronary artery disease
  • Citing Article
  • July 1992

Progress in Cardiovascular Diseases

... 22 It is important to note that several independent lines of evidence strongly suggest that most events of myocardial ischemia after noncardiac surgery are silent and caused by demand ischemia, as detected by Holter electrocardiogram monitoring or postoperative cardiac troponin elevation. [23][24][25][26][27][28] ...

Detection and Significance of Intraoperative and Postoperative Myocardial Ischemic in Peripheral Vascular Surgery
  • Citing Article
  • August 1992

JAMA The Journal of the American Medical Association

... Stable CAD and low-risk unstable angina are most commonly caused by atheromatous plaques in the coronary arteries that obstruct blood flow and may lead to the silent ischemia (30). Silent ischaemia is common and prognostically important entity (31). There is also evidence that silent myocardial ischemia is seen more frequently than anginal attacks in patients with coronary artery disease (32). ...

Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease
  • Citing Article
  • June 1991

Circulation

... Previous studies suggested that insomnia is highly comorbid with medical conditions, such as cardiovascular, respiratory, chronic pain, and so on (Dikeos and Georgantopoulos, 2011). For example, patients with cardiovascular disease are more likely to have insomnia because they may suddenly awaken with pain during sleep (Barry et al., 1991); coexisting obstructive airway disease may cause sleep disruption on account of paroxysmal nocturnal dyspnea and decrease sleep efficiency (Alonso et al., 1992). Sleep problems, chronic disease, and depression are mutually interacting, each increasing the risk for the emergence and exacerbation of the other. ...

Waking and rising at night as a trigger of myocardial ischemia
  • Citing Article
  • June 1991

The American Journal of Cardiology

... The short literature review identified several factors affecting the likelihood of death from ischaemia, such as age, sex, lifestyle, or time since the last heart attack or stroke (Pietrangelo 2018;Delgado, 2018;Raby 1990). Since all of the factors (except for time since last heart attack or stroke) are covered in the GBD database, we use it as the main data source for the exercise. ...

Long-term prognosis of myocardial ischemia detected by Holter monitoring in peripheral vascular disease
  • Citing Article
  • January 1991

The American Journal of Cardiology

... It is a risk factor for acute coronary syndromes and a strong predictor of major adverse cardiovascular events. [1][2][3][4][5] In patients undergoing noncardiac [6][7][8][9] and cardiac procedures, 10-12 perioperative anemia has been associated with worse clinical outcomes and increased incidence of perioperative myocardial infarction (MI). In patients undergoing infrainguinal bypass, anemia (hematocrit < 28%) has been associated with an increased rate of perioperative cardiac events. ...

Raby KE, Goldman L, Creager MA, Cook EF, Weisberg MC, Whittemore AD, Selwyn AD: Correlation between preoperative ischemia and major cardiac events after peripheral vascular surgery
  • Citing Article
  • December 1989

The New-England Medical Review and Journal

... During the menopausal transition, women experience a variety of physical, psychological, and social symptoms, such as depression, insomnia, osteoarthritis, and atherosclerosis. ese symptoms occur frequently and are usually associated with a worsening quality of life, both at home and at work [2][3][4]. As one of the most important therapies in the field of complementary and alternative medicine, traditional Chinese medicine (TCM) makes use of naturally occurring, plant-based ingredients that are not industrially processed. ...

Peripheral Arterial-Vascular Disease in Women: Prevalence, Prognosis, and Treatment
  • Citing Article
  • February 1995

Cardiology