The relationship between meniscal pathology and osteoarthritis depends on the type of meniscal damage visible on magnetic resonance images: data from the Osteoarthritis Initiative.

OBJECTIVE: To determine the association of different types of meniscal pathology with knee pain, bone marrow lesion (BML) volume, and end-stage knee osteoarthritis (esKOA). DESIGN: Participants were selected from an ancillary project to the Osteoarthritis Initiative (OAI) who had at least one knee with symptomatic osteoarthritis. Baseline magnetic resonance images (MRI) were evaluated for meniscal pathology using a modified International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine (ISAKOS) classification system. We collapsed 10 types of meniscal pathology into five categories: normal, intrameniscal signal, morphological deformity/extrusion (altered meniscal shape and/or extrusion but no apparent substance loss), tear, and maceration. Outcomes included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) knee pain and BML volume at baseline and after 2 years. We defined the prevalence of esKOA based on a validated algorithm. We performed logistic regression and adjusted for age, sex, and body mass index (BMI). RESULTS: The 463 participants (53% male) included in the analysis had mean age 63 (9.2) years, BMI 29.6 (4.6) kg/m2, and 71% had Kellgren-Lawrence grade ≥2. Morphological deformity/extrusion and maceration, but no other types of meniscal pathology, were associated with BML volume (morphological deformity/extrusion odds ratio [OR] = 2.47, 95% CI: 1.49, 4.09, maceration OR = 5.85, 95% CI: 3.40, 10.06) and change in BML volume (morphological deformity/extrusion OR = 2.17, 95% CI: 1.37, 3.45, maceration OR = 3.12, 95% CI: 1.87, 5.19). Only maceration was associated with baseline WOMAC knee pain (OR = 2.82, 95% CI: 1.79, 4.43) and prevalence of esKOA (OR = 7.53, 95% CI: 4.25, 13.31). CONCLUSIONS: Based on MRI, morphologic deformity/extrusion and maceration rather than intrameniscal signal or tear were associated with osteoarthritis severity and progression, which highlights the importance of differentiating distinct types of meniscal pathology.

The relationship between smoking and knee osteoarthritis in the Osteoarthritis Initiative.

OBJECTIVE: To estimate the extent that smoking history is associated with symptoms and disease progression among individuals with radiographically confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n = 2250 participants). Smoking history was assessed at baseline with 44% current or former smokers. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to measure knee pain, stiffness, and physical function. Disease progression was measured using joint space width (JSW). We used adjusted multivariable linear models to examine the relationship between smoking status and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in symptoms and JSW over time were further assessed. RESULTS: In cross-sectional analyses, compared to never-smokers high PY (≥15 PY) was associated with slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20, 95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta 0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta 0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not confirmed in the longitudinal study. Longitudinally, no associations were found between high or low PY or baseline smoking status with changes in symptoms (at 72 months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely due residual confounding. The more robust longitudinal analysis found no associations between smoking status and symptoms or JSW. Long-term smoking provides no benefits to knee OA patients while exposing them to other well-documented serious health risks.

Bone marrow lesions are associated with altered trabecular morphometry.

OBJECTIVE: Bone marrow lesions (BMLs) are a common magnetic resonance (MR) feature in patients with osteoarthritis, however their pathological basis remains poorly understood and has not been evaluated in vivo. Our aim was to evaluate the trabecular structure associated with the presence and size of BMLs present in the same regions of interest (ROI) using quantitative MR-based trabecular morphometry. DESIGN: 158 participants in the Osteoarthritis Initiative (OAI) were imaged with a coronal 3D fast imaging with steady state precession (FISP) sequence for trabecular morphometry in the same session as the OAI 3 T MR knee evaluation. The proximal medial tibial subchondral bone in the central weight-bearing ROI on these knee 3D FISP images were quantitatively evaluated for apparent bone volume fraction, trabecular number, spacing, and thickness. BMLs were also evaluated in the subchondral bone immediately adjacent to the articular cartilage. BML volume was also evaluated within the same trabecular morphometry ROI and semi-quantitatively classified as none, small, or large. Kruskal-Wallis test was used to determine if mean apparent bone volume fraction, trabecular number, spacing, or thickness differed by BML score. RESULTS: Compared to knees with ROIs containing no BMLs, knees with small or large BMLs had statistically higher apparent bone volume fraction (P < 0.01), trabecular number (P < 0.01), and thickness (P = 0.02), and lower trabecular spacing (P < 0.01). CONCLUSIONS: Compared to knees with ROIs containing no BMLs, knees with ROIs containing small or large BMLs had higher apparent bone volume fraction, trabecular number and thickness, but lower trabecular spacing. These findings may represent areas of locally increased bone remodeling or compression.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Health utilities associated with hemoglobin levels and blood loss in postmenopausal women: the Women's Health Initiative.

OBJECTIVES: The purpose of our study was to use health-related quality of life data from the Women's Health Initiative to calculate health-related utility weights and examine differences in these health utility weights across different hemoglobin (Hgb) levels. These utility weights could then be used in future cost-effectiveness studies. METHODS: Health utility weights were measured by the Short Form-6D (SF-6D), a health utility index derived from the Short Form Medical Outcomes questionnaire. Adjusted least square means were calculated for each level of Hgb at baseline and in longitudinal regression analysis the relationship between change in Hgb and change in the SF-6D was examined. Both baseline and longitudinal analyses were performed for all postmenopausal women and separately for those with self-reported heart failure, cancer, and osteoarthritis. RESULTS: Women with Hgb in the anemic range had lower health utility weights than those with higher Hgb levels. Longitudinally, a loss of of 2 g/dl Hgb or more was associated with a statistically significant and clinically meaningfully decline in SF-6D in all participants and also in the group of participants with cancer and osteoarthritis, but not in those with heart failure. CONCLUSIONS: Lower levels of Hgb and a loss of Hgb are associated with a statistically significant and clinically meaningful decrement in health utility in all postmenopausal women we studied and also in those with chronic conditions.

Comparison of BLOKS and WORMS scoring systems part I. Cross sectional comparison of methods to assess cartilage morphology, meniscal damage and bone marrow lesions on knee MRI: data from the osteoarthritis initiative.

OBJECTIVE: To compare two semiquantitative scoring systems for assessing the prevalence and severity of morphologic cartilage lesions, meniscal damage and bone marrow lesions (BMLs) from Magnetic Resonance Imagings (MRIs) of knees with osteoarthritis (OA). METHODS: From participants in the OA Initiative (OAI), a sample of 115 knees with radiographic OA at high risk of cartilage loss, were selected based on risk factors for progression. Knee MRIs were read separately using both Whole Organ MR Scoring (WORMS) and Boston-Leeds OA Knee Scoring (BLOKS), and a subset was fed back to readers for reliability. Baseline readings were used for comparison of the two methods for inter-reader reliability as well as agreement on presence/absence and severity of MRI features at both the compartment level and finer anatomical subregion levels. RESULTS: Both methods had high inter-reader agreement for all features studied (kappa for WORMS 0.69-1.0 and for BLOKS 0.65-1.0). Although the methods agreed well on presence and severity of morphological cartilage lesions (inter-method kappas from 0.66 to 0.95), BLOKS was more sensitive for full thickness defects. The two methods gave equivalent results for extent (kappa 0.74-0.80) and number (Spearman's Rho=0.85) of BMLs, and little extra information was obtained using the more complex BLOKS BML scoring. Similar results were also obtained for the common types of meniscal damage and extrusion (inter-method kappa 0.85-0.94), but the inclusion in BLOKS of meniscal signal abnormality and uncommon types of tear may be an advantage if these prove clinically meaningful. CONCLUSION: Both WORMS and BLOKS had high reliability. The two methods gave similar results in this sample for prevalence and severity of cartilage loss, BMLs and meniscal damage. Selecting between, or combining, the two methods should be based on factors such as reader effort, appropriateness for the goals of a study, and longitudinal performance.

A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men.

Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.

The effect of physician office visits on CHD risk factor modification as part of a worksite cholesterol screening program.

BACKGROUND: Elevated serum cholesterol is a major risk factor for CHD. Primary prevention through behavioral modification has been designated first-line treatment for patients with elevated cholesterol. In this study, we assessed the impact of a physician office visit after a worksite cholesterol screening on self-reported changes in diet, weight loss, exercise, and smoking. We hypothesized that those individuals who had a physician office visit regarding cholesterol would make more changes in CHD risk factors than those who did not have such a visit. METHODS: A cohort of 4,928 participants from 33 work-sites in Massachusetts and Rhode Island had baseline CHD risk factors evaluated at a cholesterol screening and 4,473 were available at follow-up 6 months later by telephone interview. A total of 1,957 had elevated cholesterol levels (>/=200 mg;/dl) and were instructed to visit their physician, in addition to receiving educational materials related to CHD risk factor modification. RESULTS: Most individuals with elevated cholesterol levels had other prevalent self-reported CHD risk factors at baseline: 58% consumed high-fat diets (>30% fat), 43% were overweight, 60% had a sedentary lifestyle (sweat-related physical activity <3 x per week), and 22% were cigarette smokers. After 6 months of follow-up, 74% of participants with high-fat diets reported eating a lower fat diet, 71% of overweight participants reported weight loss, 53% of sedentary participants attempted to increase physical activity, and 38% of smokers decreased or quit cigarette smoking. Thirty-five percent of participants completed the referral for a physician office visit to discuss their elevated cholesterol determined at the baseline worksite screening. However, these individuals showed only a modest change (which was not statistically significant) in self-reported CHD risk factors compared with those who did not have follow-up physician visits after adjusting for age, sex, race, education, occupation, medical insurance, time since last doctor visit, diabetes, and hypertension. Objective measurements of serum cholesterol, body mass index, and dietary score were likewise modestly improved and not statistically significant. CONCLUSIONS: In 6 months of follow-up, high absolute levels of CHD risk factor modification were observed after a worksite cholesterol screening. A physician office visit added only a modest but not statistically significant benefit for further CHD risk factor modification. These findings indicate that the follow-up cholesterol-related physician visit had little added clinical benefit over the screening intervention alone.

Family history and premature coronary heart disease.

BACKGROUND: We were interested in studying whether a family history of coronary heart disease (CHD) persisted as a significant risk factor for premature coronary heart disease after adjusting for traditional and nontraditional risk factors. METHODS: Ninety-five case patients with documented premature CHD (occurring in a person less than 60 years old and with greater than 50 percent occlusion of a major epicardial vessel or a documented myocardial infarction) and 95 community-based control patients were examined for risk factors including family history, hypertension, diabetes mellitus, sedentary lifestyle, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, lipoprotein(a), homocysteine, and fibrinogen. RESULTS: The risk of premature CHD for a positive family history ranged from an odds ratio (OR) of 3.25 for a standard family history of CHD in a first-degree relative, 5.9 for family history of early CHD in a first-degree relative before the age of 45 years, and 6.1 for a strong family history of CHD defined as CHD in at least two first-degree relatives. Family history persisted as a significant risk factor for premature CHD (OR = 3.9, 95 percent confidence interval [CI] 1.8-8.7) in multiple variable models that included traditional and nontraditional risk factors. It was rare, however, for a person with a positive family history not to have at least two other traditional or nontraditional risk factors. CONCLUSIONS: Family history of CHD should not be considered a simple binary risk factor for premature CHD, and a positive family history of CHD indicates that a person is at high risk for premature CHD independent of traditional and nontraditional risk factors.

Sedentary lifestyle and risk of coronary heart disease in women.

Relatively few studies have assessed the prospective relationship of sedentary lifestyle and coronary heart disease (CHD) in women. We performed a nested case-control study, identifying 50 cases of acute CHD in women and 150 age-matched controls. Risk factors including sedentary lifestyle, cigarette smoking, hypertension, diabetes mellitus, total, and HDL cholesterol levels had been previously determined in this cohort using household survey techniques. The odds ratio (OR) of CHD in sedentary women was 2.1 (95% CI 1.0-4.3, P = 0.046). The odds ratio was similar (OR = 2.3, 95% CI 1.0-5.7, P = 0.051) after adjusting for potential confounders of hypertension, cigarette smoking, low HDL cholesterol, diabetes mellitus, and being U.S. born. This study suggests that sedentary lifestyle may be an independent risk factor for CHD in women, but its results are open to several contradictory interpretations. Further studies to investigate the prospective relationship of sedentary lifestyle and the risk of CHD in women are needed.

Cross-sectional relationship between diet and physical activity in two southeastern New England communities.

The hypothesis that health promotive diets associated with higher levels of habitual physical activity confound the relationship between regular physical activity and health has not been well explored in epidemiologic studies. We evaluated self-reported physical activity, Willett Food Frequency dietary data, sociodemographic and physiologic factors cross-sectionally for 2,004 household survey participants in two southeastern New England communities. We compared the dietary habits of sedentary participants (n = 964) to those of moderately active (n = 600) and very active (n = 440) participants after adjusting for age, gender, education, smoking status, year of survey, and total calories. Our results showed that moderately active and very active participants consumed more fiber, less total fat, and less saturated fat than sedentary participants (P < .01). They also consumed more vitamins (A, C, D, E), beta carotene, and calcium, (P < .01), and ate more fruits and vegetables (P < .001) than sedentary participants. We found these relationships in both New England communities studied. This association between regular physical activity and diet suggests that the relationship of habitual physical activity and chronic disease may be confounded by diet.

Self-reported physical activity predicts long-term coronary heart disease and all-cause mortalities. Twenty-one-year follow-up of the Israeli Ischemic Heart Disease Study.

OBJECTIVE: To determine whether self-reported physical activity predicts a decreased rate of coronary heart disease (CHD) and all-cause mortalities in middle-aged men when rates are adjusted for known confounders. DESIGN: Cohort Analytic Study of Israeli government employees in 1963. SUBJECTS: Eight thousand four hundred sixty-three Israeli male government employees, aged 40 years or older, representing six areas of birth, excluding those with known cardiovascular disease in either 1963 or 1965, from an original cohort of 10,059. MAIN OUTCOME MEASURE: Comparison of rates of death due to CHD and all causes, determined from death certificates in 21 years of follow-up, for subjects with different baseline levels of self-reported leisure-time and work-related physical activities measured in 1965. RESULTS: Self-reported leisure-time but not work-related physical activity was inversely related to both CHD (adjusted relative risk, 0.79; 95% confidence interval, 0.66 to 0.95) and all-cause mortalities (adjusted relative risk, 0.91; 95% confidence interval, 0.83 to 0.99). Most of the apparent benefit accrued was from light physical activity on less than a daily basis. These inverse relationships persisted after adjustment for age, systolic blood pressure, cigarette smoking, total and high-density lipoprotein cholesterol levels, body mass index, psychosocial factors, and other potential confounders. CONCLUSION: Baseline levels of self-reported leisure-time physical activity predicted a decreased rate of CHD and all-cause mortalities in employed middle-aged Israeli men followed up prospectively for 21 years.

Physical activity, physical fitness, and coronary heart disease risk factors.

The relationships between physical activity, physical fitness, and coronary heart disease risk factors measured in a large community sample were evaluated. Self-reported physical activity using a single question, maximal oxygen consumption estimates derived from the Pawtucket Heart Health Step Test, blood pressure, nonfasting lipids, and body mass index were cross-sectionally evaluated in 381 men and 556 women. The correlation of estimated maximal oxygen consumption and self-reported physical activity was modest but statistically significant (r = 0.13 in men and r = 0.19 in women). Blood pressure, body mass index, and HDL cholesterol were correlated with physical fitness (r = 0.24-0.65) and correlated to self-reported physical activity (r = 0.09-0.14). Evaluation of coronary heart disease risk factors using both physical activity and physical fitness revealed a complex relationship that generally showed a stronger relationship with measures of physical fitness than with physical activity. This study suggests that simultaneous measurement of physical activity and physical fitness may be useful in epidemiologic studies of habitual physical activity and chronic disease.

Dietary differences in smokers and nonsmokers from two southeastern New England communities.

OBJECTIVE: Previous studies based on 24-hour dietary recall data have shown that smokers tend to consume less healthful diets than nonsmokers. We tested this hypothesis using data from food frequency questionnaires (FFQs) in a group of men and women. DESIGN: Characteristics of smokers and nonsmokers were compared using data collected from a cross-sectional household health survey. SUBJECTS: Adults aged 18 through 64 years from two communities in southeastern New England were randomly selected for the study and interviewed in their homes by trained personnel. The interview included questions on demographic and behavioral characteristics. Height, weight, blood pressure, and serum lipids were measured using standard protocols. The Willett FFQ was completed by 1,608 of 2,531 eligible respondents who made up our study sample. STATISTICAL ANALYSES PERFORMED: Respondents were categorized as current cigarette smokers or nonsmokers. Demographic, behavioral, physiologic, and dietary characteristics were compared between smokers and nonsmokers by analysis of covariance with age as the covariate. RESULTS: Eligible respondents who did not complete the FFQ differed from respondents with respect to age, gender, smoking prevalence, and several other demographic characteristics. Smokers consumed more energy, fat, alcohol, and caffeine than nonsmokers. Smoking status was inversely associated with intake of vitamins A and C, dietary fiber, folate, and iron among women, whereas differences were smaller and not significant among men. Women who smoked consumed fewer servings of fruits and vegetables than nonsmokers, but this trend was not noted in men. The association between diet and smoking was only slightly diminished by multivariate adjustment for age, income, regular exercise, marital status, and working status but most clinically relevant associations remained. The interaction between gender and smoking was not statistically significant for most dietary variables. CONCLUSIONS: These results suggest that health promotion messages targeted to smokers should include dietary instructions, especially for women.

Teaching epidemiology and biostatistics through interactive problem solving.

Medical education should prepare students for the reasoning and decision making that are required in a physician's clinical work. The disciplines of epidemiology and biostatistics, as combined in clinical epidemiology, lend themselves very well to this purpose. A lecture course in epidemiology and biostatistics was redesigned to emphasize interactive learning through problem-solving workshops in which students worked with actual data from two epidemiologic studies. A third workshop provided experience in the critical appraisal of an epidemiologic study from the current literature. Students respond favorably to these active learning experiences, which deal with relevant contemporary health problems. The concepts of clinical epidemiology should be integrated into clinical teaching in all stages of training.

Risk factors for cardiovascular disease in U.S. medical students: the Preventive Cardiology Academic Award Collaborative Data Project.

Risk factors for cardiovascular disease are commonly obtained in freshman medical students for the purpose of increasing interest and awareness in preventive cardiology. What would be a normal range of values for this select group? This paper describes the major cardiovascular risk factors for 3,811 male and female freshman medical students from eight U.S. medical schools that were obtained in a standardized fashion as part of the Preventive Cardiology Academic Award (PCAA) programs at these institutions. The distributions of height, weight, Quetelet index, systolic and diastolic blood pressures, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol are presented for male and female medical students stratified by race into white, black, Asian, and Hispanic groups. The sex and race distributions of cardiovascular risk factors such as previously diagnosed hypertension, diabetes mellitus, smoking, lack of regular exercise (three times a week or more), oral contraceptive use in women, and family history of coronary heart disease are presented. The cardiovascular risk of freshman medical students is compared to other epidemiologic studies of young adults. The use and limitations of these race- and sex-specific data on cardiovascular risk, including physiologic measurements, are discussed in the context of educational programs for medical students and house staff in preventive cardiology.