Redefining physiological responses of moose (Alces alces) to warm environmental conditions.

We tested the concept that moose (Alces alces) begin to show signs of thermal stress at ambient air temperatures as low as 14 °C. We determined the response of Alaskan female moose to environmental conditions from May through September by measuring core body temperature, heart rate, respiration rate, rate of heat loss from exhaled air, skin temperature, and fecal and salivary glucocorticoids. Seasonal and daily patterns in moose body temperature did not passively follow the same patterns as environmental variables. We used large changes in body temperature (≥1.25 °C in 24hr) to indicate days of physiological tolerance to thermal stressors. Thermal tolerance correlated with high ambient air temperatures from the prior day and with seasonal peaks in solar radiation (June), ambient air temperature and vapor pressure (July). At midday (12:00hr), moose exhibited daily minima of body temperature, heart rate and skin temperature (difference between the ear artery and pinna) that coincided with daily maxima in respiration rate and the rate of heat lost through respiration. Salivary cortisol measured in moose during the morning was positively related to the change in air temperature during the hour prior to sample collection, while fecal glucocorticoid levels increased with increasing solar radiation during the prior day. Our results suggest that free-ranging moose do not have a static threshold of ambient air temperature at which they become heat stressed during the warm season. In early summer, body temperature of moose is influenced by the interaction of ambient temperature during the prior day with the seasonal peak of solar radiation. In late summer, moose body temperature is influenced by the interaction between ambient temperature and vapor pressure. Thermal tolerance of moose depends on the intensity and duration of daily weather parameters and the ability of the animal to use physiological and behavioral responses to dissipate heat loads.

Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report.

OBJECTIVE: To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). APPROACH AND RESULTS: AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P=0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (ß=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; P<0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (ß=0.33; 95% confidence interval, 0.15-0.52; P<0.001). CONCLUSIONS: Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden.

A TECHNIQUE FOR DEPLOYMENT OF RUMEN BOLUS TRANSMITTERS IN FREE-RANGING MOOSE ( ALCES ALCES).

Recent uses for rumen boluses, such as mortality implant transmitters (MITs), in wildlife have made it necessary to adapt deployment techniques developed for livestock. In 29 and 30 attempts to place MITs in Minnesota free-ranging moose ( Alces alces) in 2013 and 2014, respectively, success was achieved 83% and 63% of the time. In 2014, new methods for MIT deployment were evaluated in captive moose in Alaska. Mandible measurements provided guidance for selection of an appropriate-sized bolus applicator. A Schulze mouth gag was used to aid insertion of the applicator, and canola oil was used to lubricate the bolus to facilitate swallowing. Time to first swallow and time to continuous swallow following sedative reversal was measured to gauge appropriate timing for bolus administration. Using the adapted technique with trained personnel, success rates for MIT deployment were 100% (10/10) for captive moose and 88% (21/24) for free-ranging moose in Minnesota in 2015.

Benefits of migration in relation to nutritional condition and predation risk in a partially migratory moose population.

The costs and benefits of alternative migratory strategies are often framed in the context of top-down and bottom-up effects on individual fitness. This occurs because migration is considered a costly behavioral strategy that presumably confers explicit benefits to migrants in the form of either decreased predation risk (predation risk avoidance hypothesis) or increased nutrition (forage maturation hypothesis). To test these hypotheses, we studied a partially migratory moose (Alces alces) population and contrasted explicit measures of predation risk (i.e., offspring survival) and nutrition (i.e., accumulation of endogenous energy reserves) between resident and migratory subpopulations. We relied on data collected from migratory and nonmigratory radio-marked moose (n = 67) that inhabited a novel study system located in coastal Alaska between 2004 and 2010. In this area, 30% of the population resides year-round on a coastal foreland area, while 48% migrate to either a small island archipelago or a subalpine ridge system (the remainder exhibited one of six different low-occurrence strategies). Overall, we determined that accumulation of body fat during the growing season did not differ between migratory or resident modalities. However, calf survival was 2.6-2.9 times higher for individuals that migrated (survival, islands = 0.49 +/- 0.16 [mean +/- SE], n = 35; ridge = 0.52 +/- 0.16, n = 33) than those that did not (survival, resident = 0.19 +/- 0.08, n = 57). Our results support the predation risk avoidance hypotheses, and suggest that migration is a behavioral strategy that principally operates to reduce the risk of calf predation and does not confer explicit nutritional benefits. We did not directly detect trade-offs between predation risk and nutrition for migratory individuals. Yet we identify an indirect life history mechanism that may mildly dampen the apparent fitness benefits of migration. The proximate factors accounting for differences in migration-specific neonate survival are likely linked to accessibility of refugial habitats for moose at local and landscape scales, landscape factors that affect hunting efficacy of large carnivores, and interactions with rural human communities. Conservation of ungulate populations can be aided by integrating knowledge about migratory behavior, life history strategies, and factors that alter ungulate vulnerability, particularly those induced by human activity.

Trapped between food, heat, and insects: Movement of moose (Alces alces) and exposure to flies in the boreal forest of Alaska.

Moose (Alces alces) in the boreal forest habitats of Alaska are unlike other northern ungulates because they tolerate high densities of flies (Diptera) even though flies cause wounds and infections during the warm summer months. Moose move to find food and to find relief from overheating (hyperthermia) but do they avoid flies? We used GPS collars to measure the rate of movement (m⋅h-1) and the time spent (min⋅day-1) by enclosed moose in four habitats: wetlands, black spruce, early seral boreal forest, and late seral boreal forest. Fly traps were used in each habitat to quantify spatio-temporal abundance. Average daily air temperatures increased into July when peak biomass of forage for moose was greatest in early seral boreal forest habitats (424.46 vs. 25.15 kg⋅ha-1 on average in the other habitats). Average daily air temperatures were 1.7°C cooler in black spruce than other habitats, but fly abundance was greatest in black spruce (approximately 4-fold greater on average than the other habitats). Moose increased their movement rate with counts of biting flies (mosquitoes, black flies, horse and deer flies), but not non-biting flies (coprophagous flies). However, as air temperature increased (above 14.7°C) moose spent more time in fly-abundant black spruce, than early seral boreal forest, showing great tolerance for mosquitoes. Warm summer temperatures appear to cause moose to trade-off foraging in fly-sparse habitats for resting and dissipating heat in shady, wet habitats with abundant flies that adversely affect the fitness of moose.

A scoping review to identify barriers and facilitators of research participation among chiropractic faculty.

OBJECTIVE: To describe peer-reviewed literature on chiropractic faculty participation in research and identify important barriers and facilitators. METHODS: We conducted a scoping review using comprehensive searches of relevant databases from inception through November 2022. English language publications of any design were included, with search terms consisting of subject headings specific to each database and free text words related to chiropractic, faculty, and research. Primary and secondary reviewer teams performed article screening and data abstraction using Covidence software, with primary reviewers responsible for consensus. Data were entered into evidence tables and analyzed descriptively. RESULTS: A total of 330 articles were screened, with 14 deemed eligible including 8 cross-sectional/correlational studies and 6 narrative reviews/editorials. Article publication dates ranged from 1987 to 2017. No intervention studies were identified. Facilitators of chiropractic faculty research included research assignment as primary role, institutional culture promoting research, and dedicated release time. Barriers included teaching/clinic assignments, lack of incentives and mentorship, and teaching load. Qualitative results identified 5 domains impacting faculty research: demographics/professional roles; personal empowerment; research culture; institutional setting/policies; and research training. CONCLUSION: Our scoping review found a paucity of recently published articles on chiropractic faculty participation in research. Educational institutions building research capacity among chiropractic faculty must establish cultural environments where scholarship is expected, rewarded, and valued. Tangible support, such as research policies, resources, and space, advanced training, funding, and release time, must be available. Faculty are encouraged to build upon key facilitators, evaluate interventions to address barriers to chiropractic faculty research, and publish their results.

Effects of combination lipid therapy in type 2 diabetes mellitus.

BACKGROUND: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. METHODS: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS: The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction). CONCLUSIONS: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Tracking reproductive events: Hoof growth and steroid hormone concentrations in hair and hoof tissues in moose (Alces alces).

Measurements of reproductive and stress-related hormones in keratinous tissues (e.g. hair, claws, hooves, baleen) can provide a record of stress and reproductive response in wildlife. We evaluated a method to collect keratin tissue from hooves of immobilized moose (Alces alces) and validated enzyme immunoassays for measuring cortisol and progesterone in hooves and hair. We also measured the annual growth and wear rates of moose hooves. Progesterone (range: 1.0-43.7 pg/mg) and cortisol (range: 0.05-2.9 pg/mg) were measurable and showed variation among hoof samples and moose. Pregnant females had twice as high progesterone concentrations (18.00 ± 3.73 pg/mg) from hoof sample locations post breeding compared to non-pregnant moose (9.40 ± 0.25 pg/mg). Annual hoof growth differed between the front (5.58 ± 0.12 cm) and rear (4.73 ± 0.13 cm) hooves and varied by season with higher growth rates during summer which decreased into autumn and winter. Adult female hooves represented between 1.6 and 2.1 years of growth and included up to two reproductive cycles. We established a method to estimate hoof growth rate and applied this to postmortem samples and were able to detect previous pregnancies. Shoulder guard hairs grew between August and March including during late gestation; however, hair progesterone concentrations (range: 2-107.1 pg/mg) were not related to reproductive state. Hair cortisol concentrations in our study (range: 0.2-15.9 pg/mg) were within the range of values previously reported for cervids. Our study supports the use of hooves for longitudinal sampling and measuring reproductive and stress-related hormones, providing a new tool for tracking reproductive events and understanding what variables may contribute to population level changes in reproduction.

Sores of boreal moose reveal a previously unknown genetic lineage of parasitic nematode within the genus Onchocerca.

Long-standing reports of open sores on the hind legs of moose (Alces alces) have been recorded in Alaska (as well as Canada, Europe, and Michigan), eliciting concerns about causes and infection. We used histological and genomic methods to investigate the sores from 20 adult moose on the Kenai Peninsula, Alaska. We paired this with thermal imagery and molt scoring of adult moose to further describe sore formation and understand its timing. Severe, ulcerative and eosinophilic dermatitis was found in all moose with sores present, and microfilariae within intraepidermal pustules were additionally found in four samples. Genetic analysis of sores from moose revealed a previously unknown genetic lineage of Onchocerca. Adult moose molt and lose their barrier of protection against flies in June and July during peak fly activity, leaving them vulnerable and allowing the development of sores. In summary, our results indicate that the cause for the sores on the hindleg of moose is a previously unknown genetic lineage of Onchocerca, probably transmitted by black flies, in timing with the molt cycle of adult moose. These sores leave moose exposed to pathogens, making them vulnerable, and challenging their health and fitness.

The association between chronic stress type and C-reactive protein in the multi-ethnic study of atherosclerosis: does gender make a difference?

The objective of this study is to examine how chronic stress in major life domains [relationship, work, sympathetic-caregiving, financial] relates to CVD risk, operationalized using the inflammatory marker C-Reactive Protein (CRP), and whether gender differences exist. Participants were 6,583 individuals aged 45-84 years, recruited as part of the Multi-Ethnic Study of Atherosclerosis. Demographic and behavioral factors, health history, and chronic stress were self-reported. CRP was obtained through venous blood draw. In aggregate, gender by chronic stress interaction effects accounted for a significant, albeit small, amount of variance in CRP (P < .01). The sympathetic-caregiving stress by gender interaction was significant (P < .01); the work stress by gender effect approached significance (P = .05). Women with sympathetic-caregiving stress had higher CRP than those without, whereas no difference in CRP by stress group was observed for men. Findings underscore the importance of considering gender as an effect modifier in analyses of stress-CVD risk relationships.

Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01178320.

Behaviour influences thermoregulation of boreal moose during the warm season.

Management of large herbivores depends on providing habitats for forage supply and refuge from risks of temperature, predation and disease. Moose (Alces alces) accumulate body energy and nutrient stores during summer, while reducing the impact of warm temperatures through physiological and behavioural thermoregulation. Building on the animal indicator concept, we used rumen temperature sensors and GPS collars on captive moose (n = 6) kept in large natural enclosures to evaluate how behaviour and habitat selection influence the rate of change in rumen temperature during the growing season on the Kenai Peninsula, Alaska, USA. We compared movement and habitat selection of individual females during tolerance days (daily amplitude in rumen temperature was ≥1.2°C in 24 h) with those of control days (daily amplitude in rumen temperature was < 1.2°C) before and after the tolerance day. Moose moved more during tolerance days (172 m • h-1; 95% confidence intervals (CI) = 149-191 m • h-1) than on control days (151 m • h-1; 95% CI = 128-173 m • h-1). The rate of change in rumen temperature (°C • h-1) declined with low to moderate movement rates that were probably associated with foraging in all habitats. Movement only increased the rate of change in rumen temperature at high activity (~ > 500 m • h-1). Additionally, the relationship between rate of change in rumen temperature and movement rate was different during tolerance and control days in open meadow and wetland habitats. In all habitats except wetlands, the rate of change in rumen temperature increased while resting, which probably is a result of diet-induced thermogenesis. Our study demonstrates that the behavioural choices of moose on the landscape are associated with the rate of change in rumen temperature and their ability to thermoregulate. Wildlife managers must consider high-value habitats where wildlife can employ both behavioural and physiological mechanisms to tolerate warm ambient conditions in a landscape of forage, predators and pests.

Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis.

BACKGROUND: Although brachial artery flow-mediated dilation (FMD) predicts recurrent cardiovascular events, its predictive value for incident cardiovascular disease (CVD) events in adults free of CVD is not well established. We assessed the predictive value of FMD for incident CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: Brachial artery FMD was measured in a nested case-cohort sample of 3026 of 6814 subjects (mean+/-SD age, 61.2+/-9.9 years) in MESA, a population-based cohort study of adults free of clinical CVD at baseline recruited at 6 clinic sites in the United States. The sample included 50.2% female, 34.3% white, 19.7% Chinese, 20.8% black, and 25.1% Hispanic subjects. Probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and 5 years of adjudicated incident CVD events, including incident myocardial infarction, definite angina, coronary revascularization (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or other revascularization), stroke, resuscitated cardiac arrest, and CVD death. Mean (SD) FMD of the cohort was 4.4% (2.8). In probability-weighted Cox models, FMD/unit SD was significantly associated with incident cardiovascular events in the univariate model (adjusted for age and sex) (hazard ratio, 0.79; 95% confidence interval, 0.65 to 0.97; P=0.01), after adjustment for the Framingham Risk Score (FRS) (hazard ratio, 0.80; 95% confidence interval, 0.62 to 0.97; P=0.025), and in the multivariable model (hazard ratio, 0.84; 95% confidence interval, 0.71 to 0.99; P=0.04) after adjustment for age, sex, diabetes mellitus, cigarette smoking status, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, heart rate, statin use, and blood pressure medication use. The c statistic (area under the curve) values of FMD, FRS, and FRS+FMD were 0.65, 0.74, and 0.74, respectively. Compared with the FRS alone, the addition of FMD to the FRS net correctly reclassifies 52% of subjects with no incident CVD event but net incorrectly reclassifies 23% of subjects with an incident CVD event, an overall net correct reclassification of 29% (P<0.001). CONCLUSIONS: Brachial FMD is a predictor of incident cardiovascular events in population-based adults. Even though the addition of FMD to the FRS did not improve discrimination of subjects at risk of CVD events in receiver operating characteristic analysis, it improved the classification of subjects as low, intermediate, and high CVD risk compared with the FRS.

Does baseline carotid intima-media thickness modify the effect of rosuvastatin when compared with placebo on carotid intima-media thickness progression? The METEOR study.

BACKGROUND: Many studies have used carotid intima-media thickness (CIMT) measurement to study atherosclerosis and the efficacy of interventions. The placebo-controlled Measuring Effects on intima-media Thickness: an Evaluation Of Rosuvastatin (METEOR) study showed significant reduction in the progression rate of maximum CIMT with 2 years of lipid treatment in asymptomatic individuals with subclinical atherosclerosis. DESIGN: The present post-hoc subgroup analysis of METEOR was carried out to determine whether the effect of rosuvastatin treatment varied according to baseline CIMT level. METHODS: To assess the relationship between efficacy of treatment with rosuvastatin versus placebo and baseline CIMT, we analyzed the effects on the primary CIMT endpoint in participants stratified by baseline quartiles of CIMT (Q1-Q4) using all individuals with a baseline reading and at least one post-baseline CIMT reading. Statistical analysis was carried out using a multilevel repeated-measures linear mixed effects model. RESULTS: In total, 876 participants were included in the analysis. In all quartiles, progression of mean maximum CIMT was significantly slower in rosuvastatin-treated individuals as compared with placebo controls. Although the magnitude of the treatment effect appeared larger in those with the highest baseline CIMT, statistical testing indicated that the magnitude of the treatment effect did not vary significantly with levels of baseline CIMT. CONCLUSION: This subgroup analysis of the METEOR study showed that in middle-aged adults with sub-clinical atherosclerosis, rosuvastatin treatment resulted in significant reduction in mean maximum CIMT progression in four quartiles of baseline CIMT, with no evidence for difference in benefit across levels of baseline CIMT.

Is summer food intake a limiting factor for boreal browsers? Diet, temperature, and reproduction as drivers of consumption in female moose.

Food intake may limit the ability of browsing mammals to gain body mass during the growing season when the leaves and stems of woody plants are most abundant. Moose are highly productive browsers with high demands for energy and nutrients, particularly during lactation. Using an indigestible marker, we estimated dry matter intake of free ranging adult female moose with and without calves over three growing seasons. During the same period, we analyzed forage quality. Intakes were highest in late spring (280 ± 19 g·kg-0.75·d-1) when forage quality peaked; however, intakes declined by 39% throughout the summer as temperatures increased and as acid detergent fiber content of browse increased. Digestibility of dry matter declined over summer from 71% to 57% among browse. Intakes were similar for moose with and without calves. Heat loads may impair the ability of moose to consume sufficient energy and nutrients. Warming and habitat change can adversely affect browser populations when poor forage qualities and low dry matter intakes combine to suppress digestible intakes of energy and nutrients.

Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study.

BACKGROUND: The relationship between impaired brachial flow-mediated dilation (FMD) and subsequent clinical cardiovascular events is not well established, especially in older adults whose FMD is often diminished. We assessed the hypothesis that FMD predicts incident cardiovascular events in a population-based cohort of older adults. METHODS AND RESULTS: FMD was measured at the 1997 to 1998 Cardiovascular Health Study clinic visit in 2792 adults aged 72 to 98 years (82.7% white, 58.6% women) recruited at 4 clinic sites in the United States. Log-rank test and Cox proportional hazard models were used to examine the association between FMD and adjudicated cardiovascular events. A total of 674 subjects (24.1%) had an adjudicated event over the 5-year follow-up period. Event-free survival rates for cardiovascular events were significantly higher in subjects with FMD greater than the sex-specific medians than in subjects with FMD less than or equal to the sex-specific medians (78.3% versus 73.6%, log-rank P=0.006). FMD remained a significant predictor of cardiovascular events after adjustment for age, gender, diabetes mellitus, cigarette smoking, systolic and diastolic blood pressure, baseline cardiovascular disease status, and total cholesterol (hazard ratio, 0.91 [95% CI, 0.83 to 0.99], P=0.02 per unit SD of FMD) but added only approximately 1% to the prognostic accuracy of the best Cox model. Brachial artery diameter was also predictive of CV events in the adjusted Cox proportional hazard model (hazard ratio, 1.12 [95% CI, 1.02 to 1.28], P=0.025) and also added approximately 1% to the accuracy of our best Cox model. CONCLUSIONS: FMD is a predictor of future cardiovascular events but adds very little to the prognostic accuracy of traditional cardiovascular risk scores/factors in older adults. FMD and brachial artery diameter may have similar predictive values for cardiovascular events in older adults.

Azithromycin for the secondary prevention of coronary events.

BACKGROUND: Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events. METHODS: In this randomized, prospective trial, we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States. RESULTS: The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval, -13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS: A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease.

Differences in carotid arterial morphology and composition between individuals with and without obstructive coronary artery disease: a cardiovascular magnetic resonance study.

OBJECTIVE: We sought to determine differences with cardiovascular magnetic resonance (CMR) in the morphology and composition of the carotid arteries between individuals with angiographically-defined obstructive coronary artery disease (CAD, > or = 50% stenosis, cases) and those with angiographically normal coronaries (no lumen irregularities, controls). METHODS AND RESULTS: 191 participants (50.3% female; 50.8% CAD cases) were imaged with a multi-sequence, carotid CMR protocol at 1.5T. For each segment of the carotid, lumen area, wall area, total vessel area (lumen area + wall area), mean wall thickness and the presence or absence of calcification and lipid-rich necrotic core were recorded bilaterally. In male CAD cases compared to male controls, the distal bulb had a significantly smaller lumen area (60.0 +/- 3.1 vs. 79.7 +/- 3.2 mm2, p < 0.001) and total vessel area (99.6 +/- 4.0 vs. 119.8 +/- 4.1 mm2; p < 0.001), and larger mean wall thickness (1.25 +/- 0.03 vs. 1.11 +/- 0.03 mm; p = 0.002). Similarly, the internal carotid had a smaller lumen area (37.5 +/- 1.8 vs. 44.6 +/- 1.8 mm2; p = 0.006) and smaller total vessel area (64.0 +/- 2.3 vs. 70.9 +/- 2.4 mm2; p = 0.04). These metrics were not significantly different between female groups in the distal bulb and internal carotid or for either gender in the common carotid. Male CAD cases had an increased prevalence of lipid-rich necrotic core (49.0% vs. 19.6%; p = 0.003), while calcification was more prevalent in both male (46.9% vs. 17.4%; p = 0.002) and female (33.3% vs. 14.6%; p = 0.031) CAD cases compared to controls. CONCLUSION: Males with obstructive CAD compared to male controls had carotid bulbs and internal carotid arteries with smaller total vessel and lumen areas, and an increased prevalence of lipid-rich necrotic core. Carotid calcification was related to CAD status in both males and females. Carotid CMR identifies distinct morphological and compositional differences in the carotid arteries between individuals with and without angiographically-defined obstructive CAD.

An evaluation of rosuvastatin: pharmacokinetics, clinical efficacy and tolerability.

BACKGROUND: The HMG Co-A reductase inhibitors (statins) are the most efficacious agents for lowering cholesterol. Statins reduce clinical cardiovascular events and are generally well tolerated. OBJECTIVE: To review the efficacy and safety of rosuvastatin, the newest and most potent of the approved statins. METHODS: A comprehensive (PubMed) search was performed to identify relevant publications up to May 2007. RESULTS/CONCLUSIONS: Rosuvastatin reduces LDL cholesterol (LDL-C) by up to 50%, and by 70% when combined with ezetimibe. Rosuvastatin also reduces plasma triglycerides and increases HDL-C, and slows atherosclerosis progression in coronary and carotid arteries in both low-risk and high-risk individuals. Tolerability is comparable with other statins. Clinical trials to evaluate cardiovascular outcomes have recently been published (CORONA) or are underway.

Estrogen plus progestin and the risk of coronary heart disease.

BACKGROUND: Recent randomized clinical trials have suggested that estrogen plus progestin does not confer cardiac protection and may increase the risk of coronary heart disease (CHD). In this report, we provide the final results with regard to estrogen plus progestin and CHD from the Women's Health Initiative (WHI). METHODS: The WHI included a randomized primary-prevention trial of estrogen plus progestin in 16,608 postmenopausal women who were 50 to 79 years of age at base line. Participants were randomly assigned to receive conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The primary efficacy outcome of the trial was CHD (nonfatal myocardial infarction or death due to CHD). RESULTS: After a mean follow-up of 5.2 years (planned duration, 8.5 years), the data and safety monitoring board recommended terminating the estrogen-plus-progestin trial because the overall risks exceeded the benefits. Combined hormone therapy was associated with a hazard ratio for CHD of 1.24 (nominal 95 percent confidence interval, 1.00 to 1.54; 95 percent confidence interval after adjustment for sequential monitoring, 0.97 to 1.60). The elevation in risk was most apparent at one year (hazard ratio, 1.81 [95 percent confidence interval, 1.09 to 3.01]). Although higher base-line levels of low-density lipoprotein cholesterol were associated with an excess risk of CHD among women who received hormone therapy, higher base-line levels of C-reactive protein, other biomarkers, and other clinical characteristics did not significantly modify the treatment-related risk of CHD. CONCLUSIONS: Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.