Beatriz L. Rodriguez

Exercise and Physical Activity in the Prevention and Treatment of Atherosclerotic Cardiovascular Disease A Statement From the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity)

This statement was reviewed by and has received the endorsement of the American College of Sports Medicine. Regular physical activity using large muscle groups, such as walking, running, or swimming, produces cardiovascular adaptations that increase exercise capacity, endurance, and skeletal muscle strength. Habitual physical activity also prevents the development of coronary artery disease (CAD) and reduces symptoms in patients with established cardiovascular disease. There is also evidence that exercise reduces the risk of other chronic diseases, including type 2 diabetes,1 osteoporosis,2 obesity,3 depression,4 and cancer of the breast5 and colon.6 This American Heart Association (AHA) Scientific Statement for health professionals summarizes the evidence for the benefits of physical activity in the prevention and treatment of cardiovascular disease, provides suggestions to healthcare professionals for implementing physical activity programs for their patients, and identifies areas for future investigation. This statement focuses on aerobic physical activity and does not directly evaluate resistance exercises, such as weight lifting, because most of the research linking physical activity and cardiovascular disease has evaluated aerobic activity. Whenever possible, the writing group has cited summary articles or meta-analyses to support conclusions and recommendations. This evidence supports the recommendation from the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) that individuals should engage in 30 minutes or more of moderate-intensity physical activity on most (preferably all) days of the week.7 Physical activity is defined as any bodily movement produced by skeletal muscles that results in energy expenditure beyond resting expenditure. Exercise is a subset of physical activity that is planned, structured, repetitive, and purposeful in the sense that improvement or maintenance of physical fitness is the objective. Physical fitness includes cardiorespiratory fitness, muscle strength, body composition, and flexibility, comprising a set of attributes that people …

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.

FOXO3A genotype is strongly associated with human longevity

Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations.

The Burden of Diabetes Mellitus Among US Youth: Prevalence Estimates From the SEARCH for Diabetes in Youth Study

OBJECTIVE. Our goal was to estimate the prevalence of diabetes mellitus in youth <20 years of age in 2001 in the United States, according to age, gender, race/ethnicity, and diabetes type. METHODS. The SEARCH for Diabetes in Youth Study is a 6-center observational study conducting population-based ascertainment of physician-diagnosed diabetes in youth. Census-based denominators for 4 geographically based centers and enrollment data for 2 health plan-based centers were used to calculate prevalence. Age-, gender-, and racial/ethnic group-specific prevalence rates were multiplied by US population counts to estimate the total number of US youth with diabetes. RESULTS. We identified 6379 US youth with diabetes in 2001, in a population of ∼3.5 million. Crude prevalence was estimated as 1.82 cases per 1000 youth, being much lower for youth 0 to 9 years of age (0.79 cases per 1000 youth) than for those 10 to 19 years of age (2.80 cases per 1000 youth). Non-Hispanic white youth had the highest prevalence (1.06 cases per 1000 youth) in the younger group. Among 10- to 19-year-old youth, black youth (3.22 cases per 1000 youth) and non-Hispanic white youth (3.18 cases per 1000 youth) had the highest rates, followed by American Indian youth (2.28 cases per 1000 youth), Hispanic youth (2.18 cases per 1000 youth), and Asian/Pacific Islander youth (1.34 cases per 1000 youth). Among younger children, type 1 diabetes accounted for ≥80% of diabetes; among older youth, the proportion of type 2 diabetes ranged from 6% (0.19 cases per 1000 youth for non-Hispanic white youth) to 76% (1.74 cases per 1000 youth for American Indian youth). We estimated that 154369 youth had physician-diagnosed diabetes in 2001 in the United States. CONCLUSIONS. The overall prevalence estimate for diabetes in children and adolescents was ∼0.18%. Type 2 diabetes was found in all racial/ethnic groups but generally was less common than type 1, except in American Indian youth.

Effects of walking on mortality among nonsmoking retired men

BACKGROUND The potential benefit of low-intensity activity in terms of longevity among older men has not been clearly documented. We examined the association between walking and mortality in a cohort of retired men who were nonsmokers and physically capable of participating in low-intensity activities on a daily basis. METHODS We studied 707 nonsmoking retired men, 61 to 81 years of age, who were enrolled in the Honolulu Heart Program. The distance walked (miles per day) was recorded at a base-line examination, which took place between 1980 and 1982. Data on overall mortality (from any cause) were collected over a 12-year period of follow-up. RESULTS During the follow-up period, there were 208 deaths. After adjustment for age, the mortality rate among the men who walked less than 1 mile (1.6 km) per day was nearly twice that among those who walked more than 2 miles (3.2 km) per day (40.5 percent vs. 23.8 percent, P=0.001). The cumulative incidence of death after 12 years for the most active walkers was reached in less than 7 years among the men who were least active. The distance walked remained inversely related to mortality after adjustment for overall measures of activity and other risk factors (P=0.01). CONCLUSIONS Our findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate. Encouraging elderly people to walk may benefit their health.

Genetic Structure, Self-Identified Race/Ethnicity, and Confounding in Case-Control Association Studies

We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension (Family Blood Pressure Program). Subjects identified themselves as belonging to one of four major racial/ethnic groups (white, African American, East Asian, and Hispanic) and were recruited from 15 different geographic locales within the United States and Taiwan. Genetic cluster analysis of the microsatellite markers produced four major clusters, which showed near-perfect correspondence with the four self-reported race/ethnicity categories. Of 3,636 subjects of varying race/ethnicity, only 5 (0.14%) showed genetic cluster membership different from their self-identified race/ethnicity. On the other hand, we detected only modest genetic differentiation between different current geographic locales within each race/ethnicity group. Thus, ancient geographic ancestry, which is highly correlated with self-identified race/ethnicity--as opposed to current residence--is the major determinant of genetic structure in the U.S. population. Implications of this genetic structure for case-control association studies are discussed.

Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study

BACKGROUND A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

The SEARCH for Diabetes in Youth study: rationale, findings, and future directions.

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.

Effects of Walking on Coronary Heart Disease in Elderly Men: The Honolulu Heart Program

BACKGROUND Effects of walking on the risk of coronary heart disease morbidity and mortality have not been identified in the elderly. The purpose of this study was to determine whether walking is associated with a reduced risk of coronary heart disease in a sample of elderly men. METHODS AND RESULTS For this study, distance walked (mile/d) was examined at a baseline examination that occurred from 1991 to 1993 in the Honolulu Heart Program. Incident coronary heart disease from all causes was observed over a 2- to 4-year follow-up period. Subjects followed up were 2678 physically capable elderly men aged 71 to 93 years. During the course of follow-up, 109 men developed coronary heart disease. Men who walked <0.25 mile/d had a 2-fold increased risk of coronary heart disease versus those who walked >1. 5 mile/d (5.1% versus 2.5%; P<0.01). Men who walked 0.25 to 1.5 mile/d were also at a significantly higher risk of coronary heart disease than men who walked longer distances (4.5% versus 2.5%; P<0. 05). Adjustment for age and other risk factors failed to alter these findings. CONCLUSIONS Findings from the Honolulu Heart Program, which targeted physically capable elderly men, suggest that the risk of coronary heart disease is reduced with increases in distance walked. Combined with evidence that suggests that an active lifestyle reduces the risk of cardiovascular disease in younger and more diverse groups, this suggests that important health benefits could be derived by encouraging the elderly to walk.

Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth.

OBJECTIVE To forecast the number of U.S. individuals aged <20 years with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) through 2050, accounting for changing demography and diabetes incidence. RESEARCH DESIGN AND METHODS We used Markov modeling framework to generate yearly forecasts of the number of individuals in each of three states (diabetes, no diabetes, and death). We used 2001 prevalence and 2002 incidence of T1DM and T2DM from the SEARCH for Diabetes in Youth study and U.S. Census Bureau population demographic projections. Two scenarios were considered for T1DM and T2DM incidence: 1) constant incidence over time; 2) for T1DM yearly percentage increases of 3.5, 2.2, 1.8, and 2.1% by age-groups 0–4 years, 5–9 years, 10–14 years, and 15–19 years, respectively, and for T2DM a yearly 2.3% increase across all ages. RESULTS Under scenario 1, the projected number of youth with T1DM rises from 166,018 to 203,382 and with T2DM from 20,203 to 30,111, respectively, in 2010 and 2050. Under scenario 2, the number of youth with T1DM nearly triples from 179,388 in 2010 to 587,488 in 2050 (prevalence 2.13/1,000 and 5.20/1,000 [+144% increase]), with the greatest increase in youth of minority racial/ethnic groups. The number of youth with T2DM almost quadruples from 22,820 in 2010 to 84,131 in 2050; prevalence increases from 0.27/1,000 to 0.75/1,000 (+178% increase). CONCLUSIONS A linear increase in diabetes incidence could result in a substantial increase in the number of youth with T1DM and T2DM over the next 40 years, especially those of minority race/ethnicity.