Todd B. Seto

Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese-American, and White Men : A Cross-Sectional Study

OBJECTIVES We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S. BACKGROUND Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect. METHODS A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids. RESULTS Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 mum, 95% confidence interval [CI]: 21 to 57mum, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 mum, 95% CI: -1 to 46 mum, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively). CONCLUSIONS Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.

Percutaneous coronary revascularization in Elderly patients: Impact on functional status and quality of life

Ischemic heart disease affects more than 25% of persons older than 65 years of age in the United States. Although elderly patients with coronary artery disease tend to be treated less aggressively than nonelderly patients, the use of percutaneous coronary intervention (PCI) in the elderly is increasing rapidly; it more than doubled between 1979 and 1986 (1). Previous studies have examined the risks for PCI-related complications among elderly patients and found that elderly patients have a higher risk for vascular complications and in-hospital death than younger patients (2). Nonetheless, little is known about the critical outcomes of these procedures from the patients perspective. Although short- and long-term mortality rates are important outcomes to consider, PCI is generally done to improve the patients quality of life by relieving the signs and symptoms of myocardial ischemia. Improvement in quality of life may be particularly germane to older patients, for whom competing risks tend to limit any potential gains in longevity (3). We examined changes in health-related quality of life among elderly patients after PCI and compared these changes with those in nonelderly patients. Methods Study Sample Patients in this study had PCI as part of two randomized multicenter clinical trials: the Balloon versus Optimal Atherectomy Trial (BOAT; n =989), which compared directional atherectomy with balloon angioplasty (4), and the Advanced Cardiovascular System Multi-Link-Stent System Trial (ASCENT; n =1040), which compared the ACS Multi-Link stent to the PalmazSchatz stent (5). Only patients enrolled in U.S. hospitals who completed a baseline health-related quality-of-life survey (n =1789) were eligible for our substudy. Inclusion and exclusion criteria for the trials were similar. All patients had symptomatic coronary artery disease that required percutaneous revascularization of a single native coronary artery. Patients with a myocardial infarction within 5 days of treatment, stroke within the preceding 3 months, bifurcation lesions, or severe proximal tortuosity were excluded. The institutional review boards of each institution approved the studies, and all patients provided informed consent before participation. Quality-of-Life Assessment Health-related quality of life was assessed by using the physical and mental health summary scales of the Medical Outcomes Study Short-Form Survey (SF-36) (6, 7). These summary scales are standardized such that the mean ( SD) for the U.S. population is 50 10. Higher scores indicate better health. Patients in ASCENT also completed the Seattle Angina Questionnaire (SAQ), a validated disease-specific instrument that measures five health-related quality-of-life domains specific for coronary artery disease (physical functioning, anginal stability, anginal frequency, disease perception, and treatment satisfaction) (8, 9). The SAQ scores range from 0 to 100, and higher scores indicate better levels of functioning (that is, less physical limitation and less frequent angina). Baseline health-related quality of life was assessed by using self-administered questionnaires that were completed immediately before the index revascularization procedure. Follow-up measurements were obtained by surveys mailed to participants 6 months and 1 year after initial treatment. Patients who did not respond to the mailed survey within 2 weeks were administered the same instrument by telephone when possible. Statistical Analysis Baseline patient characteristics of elderly ( 70 years of age) and nonelderly (<70 years of age) patients were compared by using t-tests and Wilcoxon rank-sum tests for continuous variables and Fisher exact tests for categorical variables. Logistic regression was used to determine whether the likelihood of substantial improvement in health-related quality of life after PCI differed between elderly and nonelderly patients (10). For each health-related quality-of-life scale, each patient was classified as improved or not improved according to the level of change at which patients in previous studies had reported substantial improvement. Previous studies involving the SF-36 have demonstrated that changes in the physical component score of 3.8 points or more and changes in the mental component score of 7.2 points or more were meaningful to patients (6). For the SAQ subscales, an improvement of 10 or more points has been found to correlate with clinically meaningful changes (9) and was used to classify patients as improved or not improved for our analysis. Each regression model adjusted for patient demographic characteristics (sex, marital status, education, race or ethnicity) and medical conditions (previous myocardial infarction, congestive heart failure, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, arthritis, vision problems, number of comorbid conditions, smoking status). Standardized predicted probabilities derived from these models were used to estimate the percentage of patients in each age group who were expected to demonstrate substantial improvement after PCI. We also calculated standardized risk differences and associated confidence intervals (11). The main results were not altered in analyses that adjusted for clustering (data not shown). All analyses were done by using Stata software, version 6.0 (Stata Corp., College Station, Texas). P values less than 0.05 were considered statistically significant. Significance tests were not adjusted for multiple comparisons. All data were collected and analyzed by an independent data coordinating center (Cardiovascular Data Analysis Center, Boston, Massachusetts), without direct input from the study sponsor. Twenty percent of the data were missing because of patient nonresponse at follow-up. To examine whether our results were sensitive to differences between respondents and nonrespondents, we imputed the change scores of nonrespondents by using multiple imputation techniques (12) and re-estimated the models for the full study sample. Because the results of these sensitivity analyses were similar to our primary results, we report only the primary results. Results Of the patients who completed the baseline survey, 1445 (80%) completed the 6-month follow-up survey. These patients made up our analytic cohort. Compared with nonrespondents, respondents were more likely to be nonwhite and unmarried and were less likely to have congestive heart failure. Among respondents, the median age of the nonelderly group was 57 years (range, 38 to 69 years) and the median age of the elderly group was 74 years (range, 70 to 89 years). Compared with nonelderly patients, elderly patients were more likely to be female, white, and unmarried and were less well-educated. Elderly patients were less likely to smoke cigarettes but were more likely to have hypertension and congestive heart failure and had more comorbid conditions (data not shown). Clinical Events During the initial hospitalization and 1-year follow-up period, the incidence of major adverse cardiac events, including myocardial infarction, bypass surgery, and repeated PCI, was low in both groups. However, during the initial hospitalization, older patients were more likely than younger patients to sustain a major vascular complication (3.7% compared with 1.7%; P =0.04). Effect of Percutaneous Coronary Intervention on Health-Related Quality of Life At baseline, both elderly and nonelderly patients had substantial impairments in physical health and modest impairments in mental health relative to the overall U.S. population (Table). The SAQ subscales also demonstrated substantial physical limitations and impaired quality of life due to angina in both age groups. At 6-month follow-up, both elderly and nonelderly patients demonstrated substantial improvement in each quality-of-life domain, and these gains persisted at 1 year (Table). At both 6 months and 1 year, approximately 60% of patients reported no angina. Table. Distribution of Health-Related Quality-of-Life Scores at Baseline, 6 Months, and 1 Year In adjusted analyses, the change in health-related quality of life associated with PCI did not significantly differ between elderly and nonelderly patients (Figure). At 6-month follow-up, physical health improved substantially for 51% of elderly patients and 58% of nonelderly patients (difference, 7 percentage points [95% CI, 15 to 1 percentage point]). Similarly, mental health improved substantially for 29% of elderly patients and 30% of nonelderly patients (difference, 1 percentage point [CI, 9 to 6 percentage points]). At 6-month follow-up, most patients demonstrated substantial improvement in all three aspects of disease-specific quality of life, with nearly identical benefits regardless of age. Physical limitations related to angina improved substantially for 58% of elderly patients and 54% of younger patients (difference, 4 percentage points [CI, 7 to 13 percentage points]). Elderly and nonelderly patients demonstrated similar rates of improvement in frequency of angina (75% compared with 74% [difference, 1 percentage point; CI, 6 to 10 percentage points]) and in disease burden (77% compared with 71% [difference, 6 percentage points; CI, 6 to 10 percentage points]). Only 4% to 13% of patients reported meaningful declines in cardiovascular-specific quality of life, and the proportion did not vary with age. Similar changes were observed at 1-year follow-up as well (data not shown). Figure. Standardized estimates of the percentage of patients expected to have improvements in health-related quality of life ( QOL ) 6 months after percutaneous coronary intervention, according to age. Discussion We found that PCI resulted in substantial population-level benefits for elderly patients with regard to both physical and mental health as well as reductions in physical limitations due to angina, frequency of angina, and the perceived burden of coronary artery disease. During 6- to 12-

Ginkgo biloba for the Prevention of Severe Acute Mountain Sickness (AMS) Starting One Day before Rapid Ascent

Previous studies suggest that 5 days of prophylactic ginkgo decreases the incidence of acute mountain sickness (AMS) during gradual ascent. This trial was designed to determine if ginkgo is an effective prophylactic agent if begun 1 day prior to rapid ascent. In this double-blind, randomized, placebo-controlled trial, 26 participants residing at sea level received ginkgo (60 mg TID) or placebo starting 24 h before ascending Mauna Kea, Hawaii. Subjects were transported from sea level to the summit (4205 m) over 3 hours, including 1 hour at 2835 m. The Lake Louise Self-report Questionnaire constituted the primary outcome measure at baseline, 2835 m, and after 4 h at 4205 m. AMS was defined as a Lake Louise Self-report Score (LLSR) >/= 3 with headache. Subjects who developed severe AMS were promptly transported to lower altitude for the remainder of the study. The ginkgo (n = 12) and placebo (n = 14) groups were well matched (58% vs. 50% female; median age 28 yr, range 22-53 vs. 33 yr, range 21-53; 58% vs. 57% Caucasian). Two (17%) subjects on ginkgo and nine (64%) on placebo developed severe AMS and required descent for their safety (p = 0.021); all recovered without sequelae. Median LLSR at 4205 m was significantly lower for ginkgo versus placebo (4, range 1-8 vs. 5, range 2-9, p = 0.03). Ginkgo use did not reach statistical significance for lowering incidence of AMS compared with placebo (ginkgo 7/12, 58.3% vs. placebo 13/14, 92.9%, p = 0.07). Twenty-one of 26 (81%) subjects developed AMS overall. This is the first study to demonstrate that 1 day of pretreatment with ginkgo 60 mg TID may significantly reduce the severity of AMS prior to rapid ascent from sea level to 4205 m.

Non-contact respiratory rate measurement validation for hospitalized patients

This paper presents the first clinical results for validating the accuracy of respiratory rate obtained for hospitalized patients using a non-contact, low power 2.4 GHz Doppler radar system. Twenty-four patients were measured in this study. The respiratory rate accuracy was benchmarked against the respiratory rate obtained using Welch Allyn Propaq Encore model 242, the Embla Embletta system with Universal XactTrace respiratory effort sensor and Somnologica for Embletta software, and by counting chest excursions. The 95% limits of agreement between the Doppler radar and reference measurements fall within +/-5 breaths per minute.

Aortic stiffness and calcification in men in a population-based international study.

OBJECTIVES Aortic stiffness, a hallmark of vascular aging, is an independent risk factor of cardiovascular disease and all-cause mortality. The association of aortic stiffness with aortic calcification in middle-aged general population remains unknown although studies in patients with end-stage renal disease or elderly subjects suggest that aortic calcification is an important determinant of aortic stiffness. The goal of this study was to examine the association of aortic calcification and stiffness in multi-ethnic population-based samples of relatively young men. METHODS We examined the association in 906 men aged 40-49 (81 Black Americans, 276 Japanese Americans, 258 White Americans and 291 Koreans). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using an automated waveform analyzer. Aortic calcification from aortic arch to iliac bifurcation was evaluated using electron-beam computed tomography. RESULTS Aortic calcium score was calculated and was categorized into four groups: zero (n=303), 1-100 (n=411), 101-300 (n=110), and 401+ (n=82). Aortic calcification category had a significant positive association with cfPWV after adjusting for age, race, and mean arterial pressure (mean (standard error) of cfPWV (cm/s) from the lowest to highest categories: 836 (10), 850 (9), 877 (17) and 941 (19), P for trend <0.001). The significant positive association remained after further adjusting for other cardiovascular risk factors. The significant positive association was also observed in each race group. CONCLUSIONS The results suggest that aortic calcification can be one mechanism for aortic stiffness and that the association of aortic calcification with stiffness starts as early as the 40s.

Effect of physician gender on the prescription of estrogen replacement therapy

OBJECTIVE: To determine if women cared for by female physicians are more likely to receive postmenopausal estrogen replacement therapy than women cared for by male physicians.DESIGN: Case-control study with follow-up telephone survey.SETTING: An outpatient practice at an urban teaching hospital in Boston, Massachusetts.PARTICIPANTS: Subjects were women begun on estrogen replacement therapy during an 18-month period; controls were matched on age and month of visit. Seventy-one cases (mean age 60 years, 41% nonwhite) and 142 controls (mean age 60 years, 48% nonwhite) were identified. Fifty-two (82%) of 64 eligible case patients and 89 (80%) of 111 eligible control patients completed a follow-up telephone interview assessing their preferences for female physicians and interest in estrogen replacement therapy.MAIN RESULTS: After adjusting for potential confounders using conditional logistic regression, patients with female physicians were more likely to begin estrogen replacement therapy than those seen by male physicians (odds ratio [OR] 5.4; 95% confidence interval [CIJ 1.8, 15.3). Case patients selected their primary care physician more often than control patients and were more interested in estrogen replacement therapy. After adjusting for potential confounders including patients’ preferences to select their physician and their interest in estrogen replacement therapy, patients with female physicians were still more likely to begin estrogen replacement therapy than those seen by male physicians (OR 11.4, 95% CI 1.1, 113.6).CONCLUSIONS: We conclude that female patients are more likely to be prescribed estrogen replacement therapy if they are cared for by female physicians rather than male physicians even after accounting for patient preferences. Further research is required to determine whether these differences reflect differences in physicians’ knowledge or attitudes regarding estrogen replacement therapy or reflect gender differences in how physicians discuss estrogen replacement therapy with their patients.

Seasonal variation in coronary artery disease mortality in Hawaii : observational study

A seasonal variation in cardiac mortality has been noted in both the northern 1 2 and southern3 hemispheres, with higher death rates during winter than summer. Previous studies reporting seasonal variation in mortality from coronary artery disease examined data from regions with distinct seasonal changes in temperature. To determine whether seasonality in mortality exists in a tropical climate with little variation in temperature we examined the monthly mortality from coronary artery disease among residents of Hawaii. Hawaii consists of six main islands, with a population of 1.1 million.4 We obtained monthly rates of deaths from coronary artery disease (ICD-9 410-414) as recorded on death certificates during 1984-93 from the state of Hawaii. All non-residents of Hawaii were excluded. Because the likelihood of a diagnosis of a respiratory infection might vary by season, we used mortality from …

Long chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese men in Japan and white men in the USA: population based prospective cohort study

Objective To determine whether serum concentrations of long chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in the incidence rate of coronary artery calcification (CAC) between Japanese men in Japan and white men in the USA. Methods In a population based, prospective cohort study, 214 Japanese men and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS)=0 were re-examined for CAC in 2007–2010. Among these, 175 Japanese men and 113 white men participated in the follow-up exam. Incident cases were defined as participants with CCS≥10 at follow-up. A relative risk regression analysis was used to model the incidence rate ratio between the Japanese and white men. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline. Results Mean (SD) serum percentage of LCn3PUFA was >100% higher in Japanese men than in white men (9.08 (2.49) vs 3.84 (1.79), respectively, p<0.01). Japanese men had a significantly lower incidence rate of CAC compared to white men (0.9 vs 2.9/100 person-years, respectively, p<0.01). The incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% CI 0.150 to 0.690; p<0.01). After adjusting for age, systolic blood pressure, low density lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant (0.262, 95% CI 0.094 to 0.731; p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376, 95% CI 0.090 to 1.572; p=0.18). Conclusions LCn3PUFAs significantly contributed to the difference in the incidence of CAC between Japanese and white men.

Methamphetamine‐Associated Cardiomyopathy

Methamphetamine and related compounds are now the second most commonly used illicit substance worldwide, after cannabis. Reports of methamphetamine‐associated cardiomyopathy (MAC) are increasing, but MAC has not been well reviewed. This analysis of MAC will provide an overview of the pharmacology of methamphetamine, historical perspective and epidemiology, a review of case and clinical studies, and a summary of the proposed mechanisms for MAC. Clinically, many questions remain, including the appropriate therapeutic interventions for MAC, the incidence and prevalence of cardiac pathology in methamphetamine users, risk factors for developing MAC, and prognosis of these patients. In conclusion, recognition of the significance of MAC among physicians and other medical caregivers is important given the growing use of methamphetamine and related stimulants worldwide.

A Comparison of Echocardiographic Findings in Young Adults With Cardiomyopathy: With and Without a History of Methamphetamine Abuse

Methamphetamine is currently the most widespread illegal stimulant abused in the United States. No previous reports comparing echocardiographic findings of cardiomyopathy with and without a history of methamphetamine abuse are available.