Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis.

AIM: To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. MATERIALS AND METHODS: CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. RESULTS: Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). CONCLUSION: The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Adiponectin is independently associated with NT-proBNP: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: To investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: As many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and <0.01, respectively). There was a significant interaction between adiponectin and sex for visit 3 NT-proBNP (p-interaction < 0.01), with significantly stronger associations in men. Leptin was not associated with NT-proBNP. CONCLUSION: Higher adiponectin, but not leptin, is significantly associated with higher levels of NT-proBNP, as well as with greater longitudinal increases in NT-proBNP. The associations were stronger in men.

Abdominal aortic diameter and vascular atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: To gain insight into early mechanisms of aortic widening, we examined associations between the diameter of the abdominal aorta (AD) and cardiovascular disease (CVD) risk factors and biomarkers, as well as measures of subclinical atherosclerosis, in a multi-ethnic population. DESIGN: Cross-sectional cohort. METHODS: A total of 1926 participants (mean age 62, 50% women) underwent chest and abdomen scanning by computed tomography, ultrasound of the carotid arteries, and CVD risk factor assessment. AD was measured 5 cm above and at the bifurcation. RESULTS: In a model containing traditional CVD risk factors, biomarkers and ethnicity, only age (standardized ß = 0.97), male sex (ß = 1.88), body surface area (standardized ß = 0.92), current smoking (ß = 0.42), D-dimer levels (ß = 0.19) and hypertension (ß = 0.53) were independently and significantly associated with increasing AD (in mm) at the bifurcation; use of cholesterol-lowering medications predicted smaller AD (ß = -0.70) (P < 0.01 for all). These findings were similar for AD 5 cm above the bifurcation with one exception: compared to Caucasian-Americans, Americans of Chinese, African and Hispanic descent had significantly smaller AD 5 cm above the bifurcation (ß's = -0.59, -0.49, and -0.52, respectively, all P < 0.01), whereas AD at the bifurcation did not differ by ethnicity. Physical activity, alcohol consumption, diabetes and levels of IL-6, CRP and homocysteine were not independently associated with AD. Higher aortic and coronary artery calcium burden, but not common carotid artery intima-media thickness, were independently, but modestly (ß = 0.11 to 0.19), associated with larger AD. CONCLUSIONS: Incremental widening of the aortic diameter shared some, but not all, risk factors for occlusive vascular disease.

Diagnosis of peripheral arterial disease in general practice: can the ankle-brachial index be measured either by pulse palpation or an automatic blood pressure device?

BACKGROUND: Despite its validity as a screening test for peripheral arterial disease (PAD), and its prognostic value, the ankle-brachial index (ABI) is infrequently used in primary care, probably because a Doppler device is required, along with the requisite skill for its use. We hypothesized that ABI could be accurately measured either by pulse palpation (pABI) or automatic blood pressure devices (autoABI) instead of Doppler method (dABI). DESIGN AND METHODS: In 54 subjects, we compared the results and the intra-observer reproducibility of pABI to dABI, as well as the inter-observer reproducibility of both pABI and autoABI to dABI. Arm and ankle systolic pressures were measured by the three methods by two observers. The first observer repeated pABI and dABI measurements. The results were compared by the Student paired t-test. Reproducibility was assessed by the intra-class correlation coefficient of agreement (R) and the Bland and Altman method. RESULTS: The mean dABI obtained by the first observers was 1.03 +/- 0.26 vs. a pABI of 0.85 +/- 0.44 (p < 0.0001) and an autoABI of 1.09 +/- 0.31 (p < 0.05). The intra-observer R-coefficient was at 0.89 for dABI vs. 0.60 for pABI (p < 0.05). The inter-observer R-coefficients were 0.79 for dABI vs. 0.40 for pABI (p < 0.05) and 0.44 for autoABI (p < 0.05). CONCLUSION: Neither pulse palpation nor automatic oscillometric devices can be recommended as reliable methods for ABI measurement.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Blood pressure change and survival after age 75.

Higher diastolic pressure predicted better survival in men 75 years or older in two prior analyses in the Rancho Bernardo population. Diastolic change was implicated as a possible explanation. We studied this by assessing survival according to blood pressure change in 795 men and women aged 75 years and older at the time of a second measurement taken an average of 11 years after the first, who were then followed for 5 years. Sex-specific analyses compared participants with a diastolic decrease of 5 mm Hg or greater and participants with a systolic decrease of 10 mm Hg or greater with those whose blood pressure levels did not change or increased. In men, after adjustment for baseline pressure, a decrease in diastolic pressure of 5 mm Hg or greater was associated with higher all-cause mortality (relative risk, 2.33; 95% confidence interval, 1.39 to 3.91) and cardiovascular mortality (3.13, 1.47 to 6.66). The mortality risk was strongest in men who took antihypertensive medication and had a fall in diastolic pressure (12.33, 2.73 to 55.72) compared with treated men whose pressures did not decrease. Among men with isolated systolic hypertension, those treated whose diastolic pressure remained stable had the best survival. A systolic fall in men and a decrease in either diastolic or systolic in women was not associated with poorer survival after adjustment for baseline pressure. We conclude that a fall in diastolic pressure of 5 mm Hg was associated with poor survival in men after age 75. This risk was strongest in men who took antihypertensive medication.

Alcohol consumption and blood pressure. The lipid research clinics prevalence study.

The relationship between alcohol consumption and systolic and diastolic blood pressure (BP) was examined in 2482 men and 2301 women 20 years of age or older in nine North American populations. Men at the highest level of alcohol consumption (greater than or equal to 30 ml alcohol per day) had the highest BP, while women either at the highest level of alcohol consumption or consuming no alcohol had the highest BP. Men aged greater than or equal to 35 years of age consuming greater than or equal to 30 ml alcohol per day were 1.5 to 2 times more likely to be hypertensive than non-drinkers. Multivariate analysis showed systolic and diastolic BP in both men and women to be positively and significantly (p less than 0.05) related to alcohol consumption, and this relationship was independent of the potential confounding effects of age, obesity, cigarette smoking, regular exercise, education, and gonadal hormone use in women. The regression coefficients indicated that an average of 30 ml of alcohol per day would produce a 2 to 6 mm Hg increase in systolic BP. Analyses suggested the univariate U-shaped alcohol-BP association in women was confounded by differences in obesity and cigarette smoking in nondrinking women, and by very low alcohol consumption in hypertensive women using medication. Additional analyses indicated that alcohol consumed in the 24 hours prior to the study was much more strongly associated with elevated BP than alcohol consumed in the week prior to the study excluding the previous 24 hours. We conclude that alcohol appears to have a modest but consistent and independent effect on systolic and diastolic BP.

A community study of calorie and nutrient intake in drinkers and nondrinkers of alcohol.

Nutrient intake and alcohol consumption were studied in a 15% random sample of a predominantly white upper-middle class suburban community in Southern California. Based on 24-h dietary recall, 51% of the 691 men and women aged 30 to 90 yr in the study population had consumed an average of 30 g alcohol during the preceding 24 h. In general, alcohol-derived calories were added to the diet, and did not replace calories derived from other nutrients. Consequently, alcohol consumers had a significantly higher total caloric intake than did nondrinkers. Dietary differences were greatest in moderate drinkers, who tended to consume fewer nonalcohol-derived calories, and less of most specific nutrients. Although dietary differences in moderate drinkers were similar in men and women, statistically significant differences in women were limited to carbohydrate consumption. Moderate drinking men consumed significantly less protein, fat, carbohydrate, and cholesterol. These dietary differences suggest one mechanism whereby moderate alcohol consumption might reduce the risk of coronary heart disease. Although alcohol intake resulted in an increase in total calories consumed, alcohol drinkers were not more obese than nondrinkers. Since similar proportions of drinkers and nondrinkers exercised regularly, these data may suggest that alcohol calories are not fully utilized.

Epidemiologic aspects of lipid abnormalities.

Existing cholesterol guidelines aimed at preventing cardiovascular disease emphasize the role of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol in lipid management decisions, with a subsidiary role for high-density lipoprotein (HDL) cholesterol in guiding treatment and little role for triglycerides. In this article, epidemiologic evidence is reviewed relating to the independent value of lipid factors in prediction of cardiovascular disease risk, including TC, LDL cholesterol, HDL cholesterol, very-low-density lipoprotein (VLDL) cholesterol and triglycerides, LDL particle size ("pattern B"), and the TC/HDL-cholesterol ratio. Several observations are highlighted. Triglycerides appear to be an independent risk factor in specific populations. Postprandial triglycerides may be superior to fasting triglycerides as a predictor of risk. LDL particle size does not have independent predictive value after adjustment for triglycerides. Particular emphasis is placed on the observation that the single most predictive lipid factor is the TC/HDL-cholesterol ratio, which implicitly incorporates information on both LDL and triglycerides in the numerator. This is the best predictor both of outcome and of treatment benefit, and its predictive value appears to be maintained into older age. It is concluded that increasing emphasis should be placed on the TC/HDL cholesterol ratio in epidemiologic analyses and in monitoring patients on therapy for dyslipidemia.

IgE and cardiovascular disease. Results from a population-based study.

Because previous reports have suggested that IgE-mediated events may lead to both platelet activation and arterial spasm, a population-based study of 262 men and 315 women, aged 38 to 82, was conducted to investigate the association of serum IgE levels with myocardial infarction, stroke, and noninvasively diagnosed large-vessel peripheral arterial disease. In men with previous myocardial infarction, previous stroke, or current large-vessel peripheral arterial disease, geometric mean serum IgE levels were increased 119 percent, 164 percent, and 78 percent, respectively. These associations were statistically significant (p less than 0.05). Because IgE was positively or inversely correlated with several traditional cardiovascular disease risk factors, logistic regression was used to evaluate the independent association of IgE with any cardiovascular disease (myocardial infarction, stroke, or large-vessel peripheral arterial disease). In a model including age, cigarette smoking, fasting plasma glucose level, diastolic blood pressure, and low-density lipoprotein cholesterol level as covariates, IgE was positively and independently associated with any cardiovascular disease (p = 0.03). Similar evaluations in women revealed no correlation between IgE and cardiovascular disease by either univariate or multivariable analysis. These data indicate that IgE may be an independent marker for cardiovascular disease in men, and thus suggest IgE-mediated events may play a role in the pathogenesis of cardiovascular disease.

Epidemiology of atherosclerosis: an updated overview.

Ongoing epidemiologic research continues to provide new insight into the multifactorial etiology of atherosclerosis and coronary artery disease (CAD). Cigarette smoking remains a primary risk factor; low tar and nicotine cigarettes have apparently not contributed to a reduced incidence of CAD and cardiovascular death. The stepwise risk of increasing levels of diastolic blood pressure to cardiovascular death is well known; however, elevated systolic blood pressure may be a more potent risk factor. The benefits of treating diastolic blood pressure greater than or equal to 115 mm Hg are indisputable; the benefits of treating milder hypertension, i.e., diastolic blood pressure between 90 and 114 mm Hg, probably outweigh the risks, but controversy persists. Low-density lipoprotein cholesterol, which comprises approximately 70% of total cholesterol, is strongly associated with CAD. Studies continue to relate hypercholesterolemia and CAD, showing approximately a 2% reduction in disease for each 1% reduction in total cholesterol. The influences of diabetes mellitus, thrombosis and psychosocial factors in the genesis of CAD are reviewed, as well as the evidence supporting the synergistic hazard presented by risk-factor clusters. High-density lipoprotein cholesterol bears an inverse, protective relation to CAD. Factors affecting high-density lipoprotein levels, e.g., obesity/exercise, cigarette smoking, alcohol consumption and postmenopausal use of estrogen in women, are also reviewed in light of recent findings. Additional investigation is necessary to clarify the benefits and risks associated with the treatment or modification of known risk factors and to identify others.

Systemic atherosclerosis risk and the mandate for intervention in atherosclerotic peripheral arterial disease.

Peripheral arterial disease (PAD), characterized by obstruction of the arteries in the lower limbs, is an important manifestation of atherosclerosis. There are >10 million individuals with PAD in the United States alone, and as the overall population in developed countries ages, PAD will become increasingly prevalent. Many individuals with PAD are asymptomatic and therefore remain undiagnosed and untreated. Most patients with PAD are at high risk for having a serious coronary or cerebrovascular event. Even for patients in whom symptoms, such as leg pain, are clearly evident, current treatment strategies tend to ignore the systemic nature of the disease and do not reduce overall atherosclerotic risk. Proven medical treatment options for patients with intermittent claudication include smoking cessation, exercise, and cilostazol. Pentoxifylline appears marginally effective. Several novel therapies for PAD are currently under investigation. Of particular interest are the observations from some studies that show that lipid-lowering therapy might be of benefit to PAD patients. The results of 2 ongoing prospective trials of dyslipidemic therapy in claudicants should further clarify the benefits of reducing serum lipid levels in patients with established PAD.

Coronary disease and stroke in patients with large-vessel peripheral arterial disease.

Previous reports have indicated an excess of mortality from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in subjects with large-vessel peripheral arterial disease (LV-PAD). However, there is little information available concerning the risk of nonfatal events (morbidity) in this patient group. In a population-based study of 67 patients with LV-PAD and 408 control subjects without this condition, nonfatal CHD and stroke, and total CVD events, morbidity and mortality were evaluated in both men and women. Those with LV-PAD had a 3-fold excess of CVD morbidity at baseline compared with control subjects of the same sex. However, the absolute CVD rates were greater in men than women. During the 10 years of follow-up, women with LV-PAD had more nonfatal CVD events than men, resulting in comparable overall morbidity rates. In logistic regression models adjusted for other CVD risk factors, total CVD morbidity and mortality combined with 2.5 times as great in men and 5 times as great in women with LV-PAD as in those without peripheral arterial disease. These results suggest that the total morbidity and mortality burden are dramatically increased in both men and women with LV-PAD.

Is birth order associated with adult mortality?

The objective of this study was to determine whether birth order is associated with total or cause-specific adult mortality and whether the association differed by sex, was confounded by age, number of siblings, or socioeconomic status, or was mediated by personality, education, or health behaviors. Teachers throughout California identified intellectually gifted children as part of a prospective study begun in the 1920s by Lewis Terman. Information on birth order was available on 1162 subjects (85% of cohort) who have since been followed for over 70 years. Cox proportional hazards models indicated that birth order was not associated with adult all-cause, cardiovascular, or cancer mortality. Among women, middle children were more likely than oldest children to die from causes of death other than cardiovascular disease or cancer, although the numbers in this category were small. This study did not provide evidence that birth order is associated with adult mortality in this highly intelligent, middle-class cohort.

Selenium, retinol, retinol-binding protein, and uric acid. Associations with cancer mortality in a population-based prospective case-control study.

Using a prospective case-control study design, baseline levels of plasma selenium, retinol, and retinol-binding protein, and baseline blood uric acid levels were compared in 136 case patients who subsequently died from cancer and 238 matched control subjects. Subjects were followed for an average of 8 1/2 years. In matched analyses, selenium levels were lower in case patients with gastrointestinal or prostate cancer; retinol levels, lower in those with gastrointestinal or breast cancer; retinol-binding protein levels, lower in case patients with gastrointestinal cancer; and uric acid levels, lower in a group with "other" cancers. However, only the uric acid association with "other" cancers and the retinol-binding protein association with gastrointestinal cancer were statistically significant (P < or = .02) in conditional logistic regression analyses controlling for multiple potential covariates. Relationships for each of the substances varied by cancer site, and although some relationships were suggestive, our results point to the need for larger studies with adequate numbers for site-specific analyses.

Do known cardiovascular risk factors mediate the effect of alcohol on cardiovascular disease?

The association between alcohol intake and atherosclerotic cardiovascular disease (CVD) in epidemiological studies is consistent and shows some protection from CVD at consumption levels of one to two drinks per day, but a sharp increase in CVD associated with three or more drinks per day. Analyses of potential mediators of effects of alcohol on CVD show that it increases high density lipoprotein (HDL) cholesterol levels and favourably influences thrombotic factors, especially fibrinogen, and also fibrinolytic factors. Some evidence also suggests moderate alcohol consumption may reduce insulin resistance. However, studies also show an adverse effect of alcohol, particularly at higher doses, on blood pressure (leading to hypertension) and directly on the myocardium (leading to arrhythmias and myocardiopathy). Statistical modelling of the alcohol-CVD relationship is consistent in several studies, with a protective pathway via elevated HDL cholesterol and an adverse pathway through elevated blood pressure. Other possible mediators influenced by alcohol have not yet been examined in this type of analysis. The French Paradox has led to speculation that wine is the only protective alcoholic beverage for CVD, or at least that it has a stronger effect. Multiple non-ethanol components of wine have been studied in the laboratory and have been shown to have antioxidant or anticoagulant effects. Although wine does appear more protective in ecological studies, studies within cohorts show similar effects across alcoholic beverages, suggesting confounding in ecological studies by diet, lifestyle, or other variables. The key component of alcoholic beverages thus appears to be ethanol, consistent with the known potent effects of ethanol on HDL cholesterol and thrombotic factors. The upswing in CVD risk with three or more drinks per day is sharp and emphasizes that benefit from alcohol is limited to moderate consumption only. This upswing also cautions against any public health recommendation to drink alcohol, since many persons will not or cannot limit their intake to moderate levels.

The logistic modeling of sensitivity, specificity, and predictive value of a diagnostic test.

A method is described for modeling the sensitivity, specificity, and positive and negative predictive values of a diagnostic test. To model sensitivity and specificity, the dependent variable (Y) is defined to be the dichotomous results of the screening test, and the presence or absence of disease, as defined by the "gold standard", is included as a binary explanatory variable (X1), along with variables used to define the subgroups of interest. The sensitivity of the screening test may then be estimated using logistic regression procedures. Modeled estimates of the specificity and predictive values of the screening test may be similarly derived. Using data from a population-based study of peripheral arterial disease, the authors demonstrated empirically that this method may be useful for obtaining smoothed estimates of sensitivity, specificity, and predictive values. As an extension of this method, an approach to the modeling of the relative sensitivity of two screening tests is described, using data from a study of screening procedures for colorectal disease as an example.

IgE predicts future nonfatal myocardial infarction in men.

Established risk factors cannot explain all the variance in coronary heart disease (CHD). Immunoglobin E (IgE), a mediator of allergy, can affect platelets and arterial smooth muscle. We previously demonstrated a cross-sectional association between IgE and cardiovascular disease (CVD) in men. The present study evaluated this relationship prospectively in 278 men and 343 women followed for a mean of 8.9 years. There was an association between IgE and coronary disease in men, but not in women. There was no association for CVD, stroke, or all-cause mortality. The age-adjusted relative risk (RR) for coronary mortality in men with baseline IgE > or = 200 kU/L was 1.66 (p < or = 0.66), but for nonfatal myocardial infarction (MI) it was 6.46 (p < or = 0.01). This association was independent of smoking and other risk factors, and unrelated to allergy. Thus, elevated IgE was a strong independent prospective risk factor for nonfatal, but not fatal, MI in men.

Leisure time exercise and lipid and lipoprotein levels in an older population.

Plasma lipid and lipoprotein levels were measured in 1,019 men and 1,273 women, aged 50 to 89, who were classified according to whether they reported participation in regular strenuous exercise. In men and women, strenuous exercisers had significantly (P less than .01) higher age-adjusted high-density lipoprotein (HDL) cholesterol levels than nonstrenuous exercisers, and male strenuous exercisers also had lower plasma triglyceride levels. Adjusting for differences in cigarette smoking, alcohol consumption, or obesity did not alter these results. A subgroup of 498 consecutive men and 615 consecutive women that completed a more detailed exercise questionnaire were classified into categories of light, moderate, heavy, or no exercise. In men, age-adjusted HDL cholesterol levels were higher and triglyceride levels lower with higher exercise-intensity categories (P for trend less than .001). In the heavy exercise category, HDL cholesterol levels were 15% higher and plasma triglyceride levels were 41% lower than in the sedentary group. In women, HDL cholesterol levels were significantly higher and triglyceride levels lower at the more moderate levels of exercise. In both genders results among exercise-intensity groups did not change after adjusting for age, cigarette smoking, and alcohol consumption. In men, adjusting for obesity did not significantly alter the intergroup differences, whereas in women adjusting for body mass index or waist-to-hip ratio reduced differences in HDL cholesterol levels between exercising and sedentary participants to nonsignificance. We conclude that exercise levels attainable by older adults may significantly improve HDL cholesterol levels and could theoretically reduce the risk of ischemic heart disease.

The ankle brachial index independently predicts walking velocity and walking endurance in peripheral arterial disease.

OBJECTIVES: Maintaining function among older men and women is an important public health goal as the population lives longer with chronic disease. We report the relationships between lower extremity peripheral arterial disease (PAD), PAD severity, and PAD-related symptoms with walking velocity and endurance among men and women aged 55 and older. DESIGN: A cross-sectional design. SETTING: An academic medical center. PARTICIPANTS: Participants with PAD were men and women aged 55 and older identified from a blood flow laboratory or a general medicine practice (n = 158). Randomly selected controls without PAD were identified from the general medicine practice (n = 70). MEASUREMENTS: PAD was diagnosed and quantified using the ankle brachial index (ABI). Subjects were categorized according to whether they had severe PAD (ABI <0.40), mild to moderate PAD (ABI 0.40 to <0.90), or no PAD (ABI 0.90 to <1.50). Walking endurance was assessed with the 6-minute walk. Usual walking velocity and maximal walking velocity were assessed with "usual" and "maximal" paced 4-meter walks, respectively. RESULTS: Average distances achieved in the 6-minute walk were 1569+/-390 feet for subjects with ABI 0.90-1.50, 1192+/-368 feet for subjects with ABI 0.40 to <0.90, and 942+/-334 feet for subjects with ABI < 0.40 (trend P value < .001). Walking velocities for both the usual and maximal paced 4-meter walks were slowest among subjects with ABI < 0.40 and fastest among subjects with ABI 0.90 to <1.50. Subjects with PAD who had pain at rest had slower walking velocity and poorer walking endurance than other subjects with PAD. In multiple linear regression analyses that included subjects with PAD only, ABI level was an independent predictor of 6-minute walk performance (regression coefficient = 159 ft/0.40 ABI units, P = .011), usual paced 4-meter walk (regression coefficient = .095 meters/sec/0.40 ABI units, P = .031), and maximal paced 4-meter walk (regression coefficient = .120 meters/sec/0.40 ABI units, P = .050) adjusting for age, sex, race, leg symptoms, and comorbid diseases known to affect functioning. Pain at rest was associated independently with the maximally paced 4-meter walk (-0.201 meters/sec, P = .024), but not with the other walks. CONCLUSION: ABI level has a measurable and independent association with walking endurance and both usual and maximal walking velocity. These data suggest that PAD may impair lower extremity function by diminishing function of both Type I ("slow twitch") and Type II ("fast twitch") muscle fibers. Because walking velocity has important prognostic implications for functioning, these data also suggest that ABI may be used to identify patients at increased risk of mobility loss.