Kiang Liu

Accumulated Evidence on Fish Consumption and Coronary Heart Disease Mortality: A Meta-Analysis of Cohort Studies

Background—Results from observational studies on fish consumption and coronary heart disease (CHD) mortality are inconsistent. Methods and Results—A meta-analysis of cohort studies was conducted to examine the association between fish intake and CHD mortality. Studies were included if they provided a relative risk (RR) and corresponding 95% CI for CHD mortality in relation to fish consumption and the frequency of fish intake. A database was developed on the basis of 11 eligible studies and 13 cohorts, including 222 364 individuals with an average 11.8 years of follow-up. Pooled RR and 95% CI for CHD mortality were calculated by using both fixed-effect and random-effect models. A linear regression analysis of the log RR weighted by the inverse of variance was performed to assess the possible dose-response relation. Compared with those who never consumed fish or ate fish less than once per month, individuals with a higher intake of fish had lower CHD mortality. The pooled multivariate RRs for CHD mortality were 0.89 (95% CI, 0.79 to 1.01) for fish intake 1 to 3 times per month, 0.85 (95% CI, 0.76 to 0.96) for once per week, 0.77 (95% CI, 0.66 to 0.89) for 2 to 4 times per week, and 0.62 (95% CI, 0.46 to 0.82) for 5 or more times per week. Each 20-g/d increase in fish intake was related to a 7% lower risk of CHD mortality (P for trend=0.03). Conclusions—These results indicate that fish consumption is inversely associated with fatal CHD. Mortality from CHD may be reduced by eating fish once per week or more.

Ethnic Differences in Coronary Calcification The Multi-Ethnic Study of Atherosclerosis (MESA)

Background—There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. Methods and Results—Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). Conclusions—We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.

Fish Consumption and Incidence of Stroke A Meta-Analysis of Cohort Studies

Background and Purpose— Results from observational studies on fish consumption and risk of stroke are inconsistent. We quantitatively assessed the relationship between fish intake and incidence of stroke using a meta-analysis of cohort studies. Methods— We searched the Medline and Embase databases (1966 through October 2003) and identified 9 independent cohorts (from 8 studies) that provided a relative risk (RR) and corresponding 95% CI for total or any type of stroke in relation to fish consumption. Pooled RR and 95% CI of stroke were estimated by variance-based meta-analysis. Results— Compared with those who never consumed fish or ate fish less than once per month, the pooled RRs for total stroke were 0.91 (95% CI, 0.79 to 1.06) for individuals with fish intake 1 to 3 times per month, 0.87 (95% CI, 0.77 to 0.98) for once per week, 0.82 (95% CI, 0.72 to 0.94) for 2 to 4 times per week, and 0.69 (95% CI, 0.54 to 0.88) for ≥5 times per week (P for trend= 0.06). In stratified analyses of 3 large cohort studies with data on stroke subtypes, the pooled RRs across 5 categories of fish intake were 1.0, 0.69 (95% CI, 0.48 to 0.99), 0.68 (95% CI, 0.52 to 0.88), 0.66 (95% CI, 0.51 to 0.87), and 0.65 (95% CI, 0.46 to 0.93) for ischemic stroke (P for trend= 0.24); and 1.0, 1.47 (95% CI, 0.81 to 2.69), 1.21 (95% CI, 0.78 to 1.85), 0.89 (95% CI, 0.56 to 1.40), and 0.80 (95% CI, 0.44 to 1.47) for hemorrhagic stroke (P for trend= 0.31). Conclusions— These results suggest that intake of fish is inversely related to risk of stroke, particularly ischemic stroke. Fish consumption as seldom as 1 to 3 times per month may protect against the incidence of ischemic stroke.

Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels.

Elevated plasma levels of C-reactive protein (CRP), an inflammation-sensitive marker, have emerged as an important predictor of future cardiovascular disease and metabolic abnormalities in apparently healthy men and women. Here, we performed a systematic survey of common nucleotide variation across the genomic region encompassing the CRP gene locus. Of the common single-nucleotide polymorphisms (SNPs) identified, several in the CRP promoter region are strongly associated with CRP levels in a large cohort study of cardiovascular risk in European American and African American young adults. We also demonstrate the functional importance of these SNPs in vitro.

Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease

Key Summary Points Novel risk markers for cardiovascular disease (CVD) are often said to add independent predictive value for risk prediction, based on the finding of a significant relative risk after adjustment for traditional risk factors. However, the utility of novel risk markers for screening and risk prediction should be judged not by relative risks but by test characteristics such as sensitivity, specificity, predictive values, likelihood ratios, model calibration, c-statistics, and areas under receiver-operating characteristic curves. Inflammation has emerged as a key mediator of atherogenesis and triggering of CVD events. C-reactive protein (CRP) is a nonspecific marker of inflammation that, in healthy individuals, has been shown to be associated with future incidence of CVD. Few studies have reported test characteristics for CRP, particularly in the context of traditional risk prediction algorithms such as the Framingham risk score. In the overall adult population, CRP appears to add little to risk prediction that uses the Framingham risk score. Likewise, among subgroups of individuals predicted to be at high (>20%) or low (<10%) risk by Framingham, CRP levels contribute little further risk discrimination. Among those predicted to be at intermediate 10-year risk (10% to 20%) by Framingham, CRP levels greater than 3.0 mg/L may indicate high risk and need for more intensive preventive therapy. Many questions remain before CRP can be accepted as a standard CVD risk factor, incorporated into risk prediction algorithms, or used for universal screening. Future studies of CRP and other novel CVD risk markers should focus on test characteristics, not just relative risks, in order to better define their utility for risk prediction when added to traditional CVD risk factors. Hundreds of putative risk factors have been associated with cardiovascular disease (CVD) (1). With remarkable frequency, investigators continue to propose additional behavioral, biochemical, environmental, and genetic risk markers. Recent extensive evidence supports inflammation as a key pathogenetic mechanism in the development and progression of atherosclerosis and in triggering clinical atherothrombotic CVD events. C-reactive protein (CRP) is one possible marker of vascular inflammation, and some investigators hypothesize that CRP plays a direct role in promoting vascular inflammation, vessel damage, and clinical CVD events (2-4), although this remains controversial. Concomitantly, some experts recommend routine measurement of CRP using high-sensitivity assays as a major new population screening test for prediction of CVD risk (5, 6). Scientific (7-9) and lay (10-13) media have enthusiastically embraced, advocated, and promoted CRP for risk prediction. We believe that this enthusiasm is premature. Instead, we recommend thorough consideration of what is known about CRPs test characteristics and the effectiveness, costs, and benefits of its measurement. The literature examining CRP levels and incident cardiovascular disease among healthy individuals focuses mainly on associations between CRP and CVD, without adequately considering CRPs test characteristics and its additional utility over and above that provided by traditional risk factor measurement. In this critical review of literature published before January 2006, we use a framework for evaluating diagnostic tests in risk prediction to show what is and is not known about the role for CRP in cardiovascular risk prediction. Differences between Association and Predictive Utility Countless studies report strong, independent associations between novel risk markers and CVD. Typically, these studies find unadjusted odds ratios for disease in the range of 2.0 to 3.0, and occasionally a bit higher, for individuals with the highest compared with the lowest levels of the factor. After adjustment for age, sex, and other established CVD risk factors, the relative risks (which may be reported as rate ratios, odds ratios, or hazards ratios, depending on the study design) for the association are typically attenuated to within the range of 1.5 to 2.0. Such findings indicate that an independent association exists between the marker and disease, provided one assumes that the multivariable model adjusted for all important confounding. However, whether such an association indicates clinical utility for measuring the factor is an entirely different issue. Decisions about the predictive utility of new tests should not focus on associations and relative risks. The consequences of decision making based solely on significant associations would include screening for and treating hundreds of risk markers and risk factors. Rather, we should base decisions about the additional utility of a new test for risk prediction on the tests performance (that is, sensitivity, specificity, predictive values, and clinical likelihood ratios) in the context of existing predictors. Useful ways to examine potential additional utility in the context of existing predictors include examination of the calibration of models with the new risk factor and comparisons of the areas under receiver-operating characteristic curves (AUCs) or c-statistics for risk scores calculated without and with the novel risk marker. (See the Glossary for definitions of these and other terms relevant to test utility and prediction.) All these test characteristics must be carefully considered before it can be determined whether a novel risk marker truly adds prognostic value above that provided by existing risk prediction, whether it helps to identify and reclassify risk status appropriately, and whether it has utility across the population or only in specified subgroups. Ultimately, these characteristics will determine whether a novel prognostic screening test is useful in informing clinical decision making regarding treatment. The AUC and the c-statistic are equivalent functions of the sensitivity and specificity of a test across the spectrum of all possible cut-points defining a positive and a negative test result. They represent the ability of a test to discriminate cases from noncases. For the purposes of this review, we refer to c-statistics, although most investigators to date have published their findings as AUCs. Although reliance on the c-statistic alone as a measure of test performance has limitations (14), one can think of the c-statistic as the probability that a randomly selected person from the affected population will have a higher test score or value than a randomly selected person from the unaffected population. The c-statistic ranges from 0.50 (no discrimination beyond random chance) to 1.0 (perfect discrimination). C-statistics between 0.70 and 0.80 are considered acceptable, and those between 0.80 and 0.90 are considered excellent (15). As recently demonstrated by Pepe and colleagues (16), extremely large odds ratios are required for clinically meaningful increases in these test characteristics. For example, for a binary risk marker considered in isolation, a univariate odds ratio of 9.0 or greater would be required for excellent discrimination of cases from noncases. When the marker is considered in the context of preexisting risk factors or a risk score, multivariable (independent) odds ratios in excess of 3.0 for the marker would typically be required to increase the c-statistic (and hence improve discrimination of cases from noncases) by an additional 5% or more (16). Thus, only unusually strong, independent risk factors can markedly improve risk discrimination in the population as a whole; most new risk factors do not achieve this level of added risk above standard risk factors. It is true that 2 prediction strategies may yield the same c-statistic but have different utility. A given strategy may have a higher sensitivity at a given specificity, or vice versa. Thus, examination of the 2 receiver-operating characteristic curves and consideration of where the maximal clinical benefit lies are useful to determine the overall utility of a test in the population and for subgroups. The observation that single risk factors predict CVD risk poorly can be explained by the fact that CVD is a complex disease with multiple antecedents. Accordingly, investigators developed multivariable risk prediction algorithms to predict the absolute and relative risks for occurrence of CVD and coronary heart disease (CHD) events over the next decade (17-20). The Framingham risk score (20, 21)), which uses age, sex, total and high-density lipoprotein cholesterol levels, blood pressure, smoking, and diabetes as variables to predict risk, is widely recommended. When a model containing these traditional risk factors was applied to several diverse epidemiologic cohorts, the AUC ranged from 0.66 to 0.83 in men and from 0.72 to 0.88 in women (17). Thus, despite some contrary claims (22-24), traditional risk factors, when considered in combination, provide valuable approximations of CVD risk that are superior to approximations based on single risk factors (17,25). Given the improvement in risk discrimination provided by multivariable models, these multivariable risk estimates are the logical standard to which new risk factors must be added and compared. The National Cholesterol Education Programs Third Adult Treatment Panel (21) used a modified form of the Framingham risk score as its risk prediction tool. The panel suggested thresholds of 10-year risk on which treatment decisions regarding lipid-lowering therapy should be based, in order to match the intensity of therapy to the magnitude of absolute risk. In the panels scheme, individuals with a predicted 10-year risk for CHD less than 10% are considered to be at low risk, those with a risk of 10% to 20% are considered to be at intermediate risk, and those with a risk greater than 20% (or with existing CHD or CHD risk equivalents) are considered to be at high risk. The focus is on identifying individuals at hi

Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults

Background— Studies suggest that magnesium intake may be inversely related to risk of hypertension and type 2 diabetes mellitus and that higher intake of magnesium may decrease blood triglycerides and increase high-density lipoprotein (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated. Methods and Results— We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for trend <0.01). The inverse associations were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels. Conclusions— Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome.

Physical Activity During Daily Life and Mortality in Patients With Peripheral Arterial Disease

Background— We determined whether patients with lower-extremity peripheral arterial disease (PAD) who are more physically active during daily life have lower mortality rates than PAD patients who are less active. Methods and Results— Participants were 460 men and women with PAD (mean age 71.9±8.4 years) followed up for 57 months (interquartile range 36.6 to 61.9 months). At baseline, participants were interviewed about their physical activity. Vertical accelerometers measured physical activity continuously over 7 days in 225 participants. Analyses were adjusted for age, sex, race, body mass index, hypertension, smoking, comorbidities, total cholesterol, HDL cholesterol, leg symptoms, and ankle-brachial index. At 57-month follow-up, 134 participants (29%) had died, including 75 participants (33%) who wore accelerometers. Higher baseline physical activity levels measured by vertical accelerometer were associated with lower all-cause mortality (Ptrend=0.003). Relative to PAD participants in the highest quartile of accelerometer-measured physical activity, those in the lowest quartile had higher total mortality (hazard ratio 3.48, 95% confidence interval 1.23 to 9.87, P=0.019). Similar results were observed for the combined outcome of cardiovascular events or cardiovascular mortality (Ptrend=0.005). Higher numbers of stair flights climbed during 1 week were associated with lower total mortality (Ptrend=0.035). Conclusions— PAD patients with higher physical activity during daily life have reduced mortality and cardiovascular events compared with PAD patients with the lowest physical activity, independent of confounders. Further study is needed to determine whether interventions that increase physical activity during daily life are associated with improved survival in patients with PAD.

Urine albumin excretion and subclinical cardiovascular disease : The multi-ethnic study of atherosclerosis

We examined the association between urine albumin excretion (UAE) and common and internal carotid artery intima-media thickness (IMT), end-diastolic left ventricular (LV) mass, and coronary artery calcification (CAC) scores using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of 6814 adults aged 45 to 85 years without clinical cardiovascular disease (CVD). The mean age of the MESA participants was 62.7 years, 47% were male, and 15% had diabetes mellitus (DM). Sex-specific spot urine albumin/creatinine ratios were used to define 4 UAE categories: normal, high normal, microalbuminuria, and macroalbuminuria. CAC scores were log-transformed after adding 1 to all scores. Mean values of subclinical CVD measures were computed by level of UAE after adjustment for blood pressure, DM, and other covariates. After adjustment for all covariates, geometric mean CAC scores were higher among participants with high normal UAE (8.8; P=0.07), microalbuminuria (9.9; P=0.002), and macroalbuminuria (13.1; P=0.02) compared with normal UAE (7.4), but only microalbuminuria reached statistical significance. Mean LV mass (g/m2.7) was significantly higher in participants with high normal UAE (37.0; P=0.001), microalbuminuria (38.3; P≤0.0001), and macroalbuminuria (42.3; P≤0.0001) compared with normal UAE (36.0) after adjustment for all covariates. No significant difference in mean carotid IMT was found after adjustment for all covariates. Similar results were noted in MESA participants with and without DM. In conclusion, higher UAE, including levels below microalbuminuria, may reflect the presence of subclinical CVD among adults without established CVD.

Physical performance in peripheral arterial disease : A slower rate of decline in patients who walk more

Context Patients with lower-extremity peripheral arterial disease (PAD) benefit from supervised walking programs, but cost, travel, and other factors often limit participation. Contribution This prospective study shows that a self-directed program of walking at least 3 times per week for exercise is associated with a significantly reduced functional decline during the subsequent year in patients with PAD when compared with those who walk less frequently. Implications Self-directed walking for exercise may benefit a much larger proportion of patients with PAD than is currently being served by supervised rehabilitation programs. Cautions Observational studies, such as this one, cannot prove a causal relationship between walking frequency and functional decline. The Editors Peripheral arterial disease (PAD) of the lower extremities affects 20% to 30% of older patients in general medical practices (1, 2). Most patients with the disease do not have classical symptoms of intermittent claudication (1-3). Compared with those without PAD, persons with the disease have significantly greater functional impairment and more rapid functional decline (2-4). Exercise rehabilitation that includes supervised treadmill walking substantially improves treadmill walking performance in men and women with intermittent claudication (5). However, such barriers as cost, transportation, and program availability often limit access to exercise rehabilitation programs for patients with PAD (6, 7). Clinical guidelines for PAD recommend supervised walking exercise, but evidence for the benefits of unsupervised walking exercise is minimal to absent (8, 9). Specifically, it is unknown whether patients with PAD who engage in regular self-directed walking exercise have less functional decline than those who are sedentary. For persons with PAD, supervised treadmill walking exercise 3 or more times per week is more effective than less frequent supervised walking exercise (5). Therefore, we conducted a prospective observational study to examine whether patients with PAD who report that they walk for exercise 3 or more times per week have less functional decline than PAD participants who walk for exercise less frequently. Methods Methods for this longitudinal observational study of men and women with and without PAD have been described elsewhere (4). The protocol was approved by the institutional review boards of Northwestern University and Catholic Health Partners Hospital. Participants gave informed consent. Participant Eligibility Participants were 55 years of age and older at baseline. Potential participants were identified consecutively from patients who tested positive for PAD in 3 Chicago-area noninvasive vascular laboratories. A few participants were identified from lists of consecutive patients with recent appointments in our general internal medicine practice. This latter group of patients was screened for PAD by calculating their anklebrachial index at baseline; PAD was defined as an index of less than 0.90 (10-12). Baseline visits occurred between October 1998 and January 2000, and follow-up visits were scheduled annually. Exclusion Criteria Exclusion criteria have been previously reported (4). Patients with dementia, recent major surgery, or foot or leg amputations were excluded. We also excluded nursing home residents and wheelchair-bound patients. Patients who did not speak English were excluded because the investigators were not fluent in non-English languages. Participants who underwent leg revascularization were excluded from analyses after the procedure. AnkleBrachial Index Measurement In accordance with established methods, we used a hand-held Doppler probe (Nicolet Vascular Pocket Dop II, Golden, Colorado) to obtain systolic pressures in the right and left brachial, dorsalis pedis, and posterior tibial arteries (4, 13, 14). To maximize precision, each pressure was measured twice. We calculated the anklebrachial index in each leg by dividing the mean of all 4 dorsalis pedis and posterior tibial pressures by the mean of the 4 brachial pressures (13). When calculated by this method, the index correlates more closely with lower-extremity arterial function than when determined by alternative methods (13). We used the average brachial pressures in the arm with highest pressure when the measurement was higher in the same arm in both measurement sets and the 2 brachial pressures differed by 10 mm Hg or more in at least 1 measurement set; in such cases, subclavian stenosis was possible (13, 14). The lowest anklebrachial index was used in analyses. Leg Symptoms On the basis of a previous study (3, 4, 15), we used the San Diego Claudication Questionnaire to classify patients into 5 groups according to type of leg symptoms. Four groups had exertional leg symptoms as determined by an affirmative response to the question, Do you get pain in either leg or buttock on walking? These participants were further classified as having 1) intermittent claudication (n= 133), defined as exertional calf pain that does not begin at rest, causes the participant to stop walking, and resolves within 10 minutes of rest; 2) leg pain on exertion and rest (n= 76), defined as exertional leg pain that sometimes begins at rest; 3) atypical exertional leg pain/carry on (n= 39), defined as exertional leg symptoms that do not begin at rest and do not stop the individual while walking; and 4) atypical exertional leg pain/stop (n= 89), defined as exertional leg symptoms that do not begin at rest, stop the individual from walking, and do not involve the calves or resolve within 10 minutes of rest. A fifth group of patients was defined as asymptomatic (n= 80) because they reported no pain in either leg or buttock on walking. Comorbid Conditions We used algorithms developed for the Womens Health and Aging Study to document the following comorbid conditions: angina, diabetes mellitus, myocardial infarction, stroke, heart failure, pulmonary disease, spinal stenosis, disk disease, Parkinson disease, and hip fracture (16). American College of Rheumatology criteria were used to diagnose knee and hip osteoarthritis (17, 18). Functional Measures Rationale for use of the specific functional outcome measures used in the Walking and Leg Circulation Study has been described previously (19). Timed Walk Per a standardized protocol (20, 21), participants walked up and down a 100-foot hallway for 6 minutes after they were instructed to cover as much distance as possible during the allotted time. Repeated Chair Rises Participants sat in a straight-backed chair with their arms folded across their chest and rose to a standing position, repeating the exercise 5 consecutive times as quickly as possible. We measured the time each patient required to complete 5 chair rises. Standing Balance Participants were asked to hold 3 increasingly difficult standing positions for 10 seconds each: standing with feet together and parallel (side-by-side stand); standing with feet parallel, with the toes of 1 foot adjacent to and touching the heel of the opposite foot (semi-tandem stand); and standing with 1 foot directly in front of the other (tandem stand) (22, 23). Walking Velocity Walking velocity was measured with a 4-meter walk performed at usual and fastest pace. For the usual-paced walk, participants were instructed to walk at their usual pace, as if going down the street to the store. For the fastest-paced walk, participants were instructed to walk as fast as they could. Each walk was demonstrated by the research assistant. Participants were given the command ready, go; timing began on go. Each walk was performed twice, and the faster time in each pair was used in analyses (22, 23). Summary Performance Score The summary performance score combined data from the usual-paced 4-meter walking velocity, time to rise from a seated position 5 times, and standing balance. Individuals received a score of 0 for each task they were unable to complete. Scores ranging from 1 to 4 were assigned for all completed tasks; the scoring system was based on quartiles of performance for over 5000 participants in the Established Populations for the Epidemiologic Study of the Elderly (22, 23). Scores were then summed to obtain the summary performance score, which ranged from 0 to 12. Exercise During each study visit, participants were classified as current exercisers if they responded affirmatively to the question, During the past 2 weeks, have you gone walking for exercise? Frequency and duration of walking for exercise were also determined at each visit. A minimum frequency of 3 times per week and a minimum duration of 30 minutes per session are most optimal for supervised walking exercise programs in patients with PAD according to published literature (5). Therefore, we defined optimal walking frequency as 3 or more times per week and optimal walking duration as 90 minutes per week. Depressive Symptoms We measured depressive symptoms annually by using the Geriatric Depression Scale (short form), a 15-item questionnaire (24). Possible scores for the questionnaire ranged from 0 to 15; a score of 0 indicated no depressive symptoms and a score of 15 indicated that all depressive symptoms defined in the questionnaire were present. Other Measures Height and weight were measured at each visit. Body mass index (BMI) was calculated by dividing the patients body weight in kilograms by the square of his or her height in meters. Patients annually reported cigarette use (pack-years) and the number of blocks they walked during the past week. The principal investigator reviewed all medication use to identify patients who used aspirin, statins, and angiotensin-converting enzyme inhibitors. Physical Activity We measured each patients physical activity continuously over 7 days (beginning with the baseline visit) by using the Caltrac (Muscle Dynamics Fitness Network, Torrance, California) vertical accelerometer (25-29). This accelerometer

Blood Pressure Differences Between Northern and Southern Chinese: Role of Dietary Factors: The International Study on Macronutrients and Blood Pressure

Blood pressure and prevalence of high blood pressure are greater for northern than southern Chinese. Reasons for these differences are unclear. Relationships of north–south blood pressure differences with multiple dietary factors were investigated in 839 Chinese participants, International Study on Macronutrients and Blood Pressure (INTERMAP), 561 northern, 278 southern, aged 40 to 59 years. Daily nutrient intakes were determined from four 24-hour dietary recalls and 2 timed 24-hour urine collections. Average systolic/diastolic pressure levels were 7.4/6.9 mm Hg higher for northern than southern participants. Southern participants had lower body mass index, sodium intake, sodium/potassium ratio, and higher intake of calcium, magnesium, phosphorus, and vitamins A and C. Considered singly, with control for age and gender, several dietary variables (eg, body mass index, urinary sodium/potassium ratio, urinary sodium, dietary phosphorus, and magnesium) reduced north–south blood pressure differences by ≥10%. Controlled for age and gender, nondietary variables had little effect on north–south blood pressure differences. With inclusion in regression models of multiple dietary variables (sodium, potassium, magnesium or phosphorus, body mass index), north–south blood pressure differences became much smaller (systolic −1.1, diastolic 1.6 mm Hg) and statistically nonsignificant. In conclusion, multiple dietary factors accounted importantly for north–south blood pressure differences. Efforts are needed to improve nutrition in China, especially in the north, as well as in other populations including those in the United States, for prevention and control of adverse blood pressure levels and major adult cardiovascular disease.