Biomedical subjects

A R Folsom

Publications and source records attributed to A R Folsom.

At least 37 records · Page 2Linked to original sources

PubMed2001

Association of C-reactive protein with markers of prevalent atherosclerotic disease.

Recent prospective studies have demonstrated that elevated C-reactive protein (CRP) is a marker of increased risk of atherothrombotic clinical events. We examined in a large, cross-sectional family-based study (n = 875 men, 948 women) whether serum CRP was associated with prevalent coronary heart disease (CHD), the ankle/brachial blood pressure index, or carotid intima-media thickness, an indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP was associated with many other cardiovascular risk factors, particularly markers of obesity and insulin resistance, markers of inflammation and acute phase reaction, and hormone replacement therapy. Adjusted for age and family type, there was a weak positive association of CRP with carotid intima-media thickness in both genders and with prevalent CHD in women. However, adjustment for other risk factors completely eliminated the associations. For example, among women, the risk factor-adjusted mean values of intima-media thickness across quartiles of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak inverse association between CRP and ankle/brachial blood pressure index, independent of other risk factors, but no such association in women. Our findings indicate that CRP is not strongly and independently associated with prevalent atherosclerosis. Because CRP has been associated with clinical events, it could be that elevated CRP may be a stronger marker of thrombotic risk than of the degree of atherosclerosis.

Age Factors↗

PubMed2001

Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey.

BACKGROUND: Coronary heart disease (CHD) mortality continued to decline from 1985 to 1997. METHODS AND RESULTS: We tabulated CHD deaths (ICD-9 codes 410 through 414) in the Minneapolis/St Paul, Minnesota, area. For 1985, 1990, and 1995, trained nurses abstracted the hospital records of patients 30 to 74 years old with a discharge diagnosis of acute CHD (ICD-9 codes 410 or 411). Acute myocardial infarction (AMI) events were validated and followed for 3-year all-cause mortality. Between 1985 and 1997, age-adjusted CHD mortality rates in Minneapolis/St Paul fell 47% and 51% in men and women, respectively; the comparable declines in US whites were 34% and 29%. In-hospital mortality declined faster than out-of-hospital mortality. The rate of AMI (ICD-9 code 410) hospital discharges declined almost 20% between 1985 and 1995, whereas the discharge rate for unstable angina (ICD-9 code 411) increased substantially. The incidence of hospitalized definite AMI declined approximately 10%, whereas recurrence rates fell 20% to 30%. Three-year case fatality rates after hospitalized AMI decreased consistently by 31% and 41% in men and women, respectively. In-hospital administration of thrombolytic therapy, emergency angioplasty, ACE inhibitors, beta-blockers, heparin, and aspirin increased greatly. CONCLUSIONS: Declining out-of-hospital death rates, declining incidence and recurrence of AMI in the population, and marked improvements in the survival of AMI patients all contributed to the 1985 to 1997 decline of CHD mortality in the Minneapolis/St Paul metropolitan area. The effects of early and late medical care seem to have had the greatest contribution to rates during this time period.

Acute Disease↗

PubMed2001

Types of dietary fat and breast cancer: a pooled analysis of cohort studies.

Recently, there has been interest in whether intakes of specific types of fat are associated with breast cancer risk independently of other types of fat, but results have been inconsistent. We identified 8 prospective studies that met predefined criteria and analyzed their primary data using a standardized approach. Holding total energy intake constant, we calculated relative risks for increments of 5% of energy for each type of fat compared with an equivalent amount of energy from carbohydrates or from other types of fat. We combined study-specific relative risks using a random effects model. In the pooled database, 7,329 incident invasive breast cancer cases occurred among 351,821 women. The pooled relative risks (95% confidence intervals [CI]) for an increment of 5% of energy were 1.09 (1.00-1.19) for saturated, 0.93 (0.84-1.03) for monounsaturated and 1.05 (0.96-1.16) for polyunsaturated fat compared with equivalent energy intake from carbohydrates. For a 5% of energy increment, the relative risks were 1.18 (95% CI 0.99-1.42) for substituting saturated for monounsaturated fat, 0.98 (95% CI 0.85-1.12) for substituting saturated for polyunsaturated fat and 0.87 (95% CI 0.73-1.02) for substituting monounsaturated for polyunsaturated fat. No associations were observed for animal or vegetable fat intakes. These associations were not modified by menopausal status. These data are suggestive of only a weak positive association with substitution of saturated fat for carbohydrate consumption; none of the other types of fat examined was significantly associated with breast cancer risk relative to an equivalent reduction in carbohydrate consumption.

Breast Neoplasms↗

PubMed2001

Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.

BACKGROUND: Thrombomodulin (TM) is expressed on the endothelial surface and plays an important role in vasoprotection. A common polymorphism of TM at amino acid position 455 with an alanine (A) to valine (V) transition was previously reported to be associated cross-sectionally with acute myocardial infarction. Whether this single nucleotide polymorphism predicts risk of developing coronary heart disease (CHD) is unclear. METHODS AND RESULTS: Within a large cohort study, we identified 467 incident CHD cases during an average of 5 years of follow-up. We determined TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample of 461. The AA genotype was significantly more prevalent in noncases than in cases (P:=0.016). The prevalences of the AA genotype in noncase blacks and whites were 93% and 67%, respectively. The AA genotype frequency was significantly reduced in black cases versus noncases (P:=0.018). It was also lower in white cases than in noncases, but the difference was not statistically significant (P:=0.066). Weighted proportional hazards regression analysis after adjustment for age, sex, and other CHD risk factors showed that having the V allele increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks but did not significantly increase the risk in whites. CONCLUSIONS: The TM A455V polymorphism predicts risk of developing CHD in blacks.

Adult↗

PubMed2001

Interaction of the glutathione S-transferase genes and cigarette smoking on risk of lower extremity arterial disease: the Atherosclerosis Risk in Communities (ARIC) study.

Glutathione S-transferases M1 or T1 (GSTM1/GSTT1) affect the body's ability either to detoxify or to activate chemicals in cigarette smoke. Cigarette smoking increases the risk of lower extremity arterial disease (LEAD). We conducted a cross-sectional study to evaluate a hypothesized interaction of the genetic polymorphisms of GSTM1 and T1 with cigarette smoking in the risk of LEAD in the ARIC study. A stratified-random sample, including 212 LEAD cases (ankle-brachial index <0.9 in men or <0.85 in women) and 1277 non-cases, was selected from the ARIC cohort of 12041 middle-aged participants free of CHD, transient ischemic attack and stroke at baseline (1987-1989). Overall, the differences in the frequencies of GSTM1-0 and GSTT1-0 (the homozygous deletion genotype) were not statistically significant between cases and non-cases (44 vs. 41% and 28 vs. 18%). However, smoking was more prevalent among LEAD cases than non-cases. The results suggest that the non-deletion genotype GSTM1-1 interacts with smoking to increase the risk of LEAD, but this interaction was not statistically significant. The functional genotype GSTT1-1 was significantly associated with increased risk of LEAD given smoking after adjustment for other risk factors. In individuals with GSTT1-1, the odds ratios (ORs) (95% confidence intervals) of LEAD were 3.6 (1.4, 9.0) for current smoking and 5.0 (1.9, 13.0) for 20+ pack-years. However, in those with GSTT1-0, the ORs were 0.8 (0.2, 2.8) for current smoking and 0.6 (0.1, 2.1) for 20+ pack-years. The interaction was significant (P<0.05) on the additive scale for current smoking and on both the additive and multiplicative scales for 20+ pack-years. Among non-smokers, GSTT1-1 was not associated with LEAD. The results suggest that the GSTT1-1 polymorphism may be a susceptibility factor modifying the risk of LEAD associated with cigarette smoking.

Arteriosclerosis↗

PubMed2001

Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study.

Inflammation is thought to play a central role in the etiology and outcome of atherosclerosis. Animal studies as well as in vitro and in vivo human studies suggest that host factors modulate the magnitude and extent of inflammatory responses. We investigated familial aggregation of three systemic markers of inflammation (C-reactive protein (CRP), white blood cell count (WBC), and albumin) in a large, cross-sectional study conducted in four US communities. We found evidence of substantial heritability (35-40%) for CRP levels as well as for WBC and albumin levels. Negligible spouse correlations suggested little influence of shared household environment on these traits. The combination of sociodemographic factors (age, center, education), behavioral and lifestyle factors (cigarette smoking, alcohol intake, hormone replacement therapy), obesity and fat patterning, and prevalent diabetes explained 13-30% the interindividual variability of these traits. There was no evidence that these inflammation phenotypes were linked to a microsatellite marker in the interleukin-1 gene cluster on chromosome 2q, a region that includes several candidate genes for chronic inflammatory diseases. Our findings suggest that CRP levels, albumin levels, and WBC are determined at least partially by genetic factors. Further efforts to identify gene loci affecting these traits are warranted.

Adult↗

PubMed2001

A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study.

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk=1.60, 95% CI 0.9-2.9). After adjusting for other confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and triglycerides), the association became stronger (relative risk=2.70, 95% CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.

Cohort Studies↗

PubMed2001

Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies.

CONTEXT: Some epidemiologic studies suggest that elevated fruit and vegetable consumption is associated with a reduced risk of breast cancer. However, most have been case-control studies in which recall and selection bias may influence the results. Additionally, publication bias may have influenced the literature on associations for specific fruit and vegetable subgroups. OBJECTIVE: To examine the association between breast cancer and total and specific fruit and vegetable group intakes using standardized exposure definitions. DATA SOURCES/STUDY SELECTION: Eight prospective studies that had at least 200 incident breast cancer cases, assessed usual dietary intake, and completed a validation study of the diet assessment method or a closely related instrument were included in these analyses. DATA EXTRACTION: Using the primary data from each of the studies, we calculated study-specific relative risks (RRs) that were combined using a random-effects model. DATA SYNTHESIS: The studies included 7377 incident invasive breast cancer cases occurring among 351 825 women whose diet was analyzed at baseline. For comparisons of the highest vs lowest quartiles of intake, weak, nonsignificant associations were observed for total fruits (pooled multivariate RR, 0.93; 95% confidence interval [CI], 0.86-1.00; P for trend =.08), total vegetables (RR, 0.96; 95% CI, 0.89-1.04; P for trend =.54), and total fruits and vegetables (RR, 0.93; 95% CI, 0.86-1.00; P for trend =.12). No additional benefit was apparent in comparisons of the highest and lowest deciles of intake. No associations were observed for green leafy vegetables, 8 botanical groups, and 17 specific fruits and vegetables. CONCLUSION: These results suggest that fruit and vegetable consumption during adulthood is not significantly associated with reduced breast cancer risk.

Adult↗

PubMed2001

Menstrual history and risk of hip fractures in postmenopausal women. The Iowa Women's Health Study.

The authors examined prospectively between 1986 and 1997 the relation of irregular menstrual cycles and irregular menstrual bleeding duration earlier in life with risk of hip fracture in 33,434 postmenopausal Iowa women. Over the 318,522 person-years of follow-up, 523 hip fractures were reported. Adjusted for age, smoking, body mass index, waist/hip ratio, and estrogen use, the relative risk of hip fracture in women who reported always having irregular menstrual cycles, compared with women who never had irregular cycles, was 1.36 (95% confidence interval (CI): 1.03, 1.78). Women who reported having irregular menstrual bleeding duration had a 1.40-fold (95% CI: 1.10, 1.78) increased risk of hip fracture compared with women with regular bleeding duration. In addition, women who reported having both irregular menstrual cycles and irregular menstrual bleeding had a 1.82-fold (95% CI: 1.55, 2.15) higher risk of hip fracture than did women who reported neither irregularity. Women who reported only one menstrual disturbance did not have a risk of hip fracture that was significantly different from women who reported no menstrual disturbances. The authors conclude that women with menstrual irregularities are at increased risk of hip fracture, probably because they are estrogen or progesterone deficient.

Aged↗

PubMed2001

Cardiovascular risk factors and cognitive decline in middle-aged adults.

OBJECTIVE: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. METHODS: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. RESULTS: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. CONCLUSIONS: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Adult↗

PubMed2001

Cross-sectional association of soluble thrombomodulin with mild peripheral artery disease; the ARIC study. Atherosclerosis Risk in Communities.

Thrombomodulin, an endothelial membrane glycoprotein, is an essential part of the protein C anti-coagulant pathway. It may also have a role in the regulation of fibrinolysis. We carried out a cross-sectional study to assess the association of soluble thrombomodulin (sTM) with peripheral artery disease (PAD) in a stratified random sample (n=863) of otherwise healthy black and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. PAD was more common in black than in white participants and associated with classical risk factors in an expected manner; positively with age, smoking, hypertension, diabetes (P=0.05), and LDL-cholesterol, and inversely with HDL-cholesterol. Significant positive associations were observed also with fibrinogen and white blood cell count. Overall, the sTM concentration was not a significant predictor of PAD. The association was, however, modified by the level of factor VIII:C in whites (P=0.002 for the interaction), but not in blacks. Protein C was inversely associated with PAD prevalence (odds ratio 0.33, 95% CI 0.18--0.61, P=0.0004). sTM was inversely associated with plasminogen, but no associations with t-PA, PAI-1, or D-dimer were seen. In conclusion, the present results provide some additional evidence on the role of thrombomodulin-protein C pathway in atherosclerotic disease and support our earlier observation on interaction between sTM and factor VIII:C.

Black or African American↗

PubMed2001

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts CHD.

The relationship between carotid artery lesions (CALs), with and without acoustic shadowing (AS) as an index of arterial mineralization, and incident coronary heart disease (CHD) was examined in the Atherosclerosis Risk in Communities study cohort. Among 12,375 individuals, ages 45-64 years, free of CHD at baseline, 399 CHD events occurred between 1987-1995. In a 3-cm segment centered at the carotid bifurcation, CALs with and without AS were identified by B-mode ultrasound (US). After adjustment for the major CHD risk factors, the CHD hazard ratio (HR) for women with CAL without AS compared to women without CAL was 1.78 (95% CI: 1.22, 2.60) and the HR comparing women with CAL with AS to women with CAL without AS was 1.73 (95% CI: 1.07, 2.80). Corresponding HRs for men were 1.59 (95% CI: 1.22, 2.07) and 1.04 (95% CI: 0.72, 1.51). CALs predicted CHD events; this association was stronger for mineralized CALs in women, but not men.

Calcinosis↗

PubMed2001

Validation of death certificate diagnosis for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.

The validity of the death certificate in identifying coronary heart disease deaths was evaluated using data from the community surveillance component of the Atherosclerosis Risk in Communities Study (ARIC). Deaths in the four ARIC communities of Forsyth Co., NC; Jackson, MS; Minneapolis, MN; and Washington Co., MD were selected based on underlying cause of death codes as determined by the rules of the ninth revision of the International Classification of Diseases (ICD-9). Information about the deaths was gathered through informant interviews, physician or coroner questionnaires, and medical record abstraction, and was used to validate the cause of death. Sensitivity, specificity, and positive predictive value of the death certificate classification of CHD death (ICD-9 codes 410-414 and 429.2) were estimated by comparison with the validated cause of death based on physician review of all available information. Results from 9 years of surveillance included a positive predictive value 0.67 (95% CI 0.66-0.68), sensitivity of 0.81 (95% CI 0.79-0.83), and a false-positive rate (1-specificity) of 0.28 (95% CI 0.26-0.30). Comparing CHD deaths as defined by the death certificate with validated CHD deaths indicated that the death certificate overestimated CHD mortality by approximately 20% in the ARIC communities. Within subgroups, death certificate overestimation was reduced with advancing age (up to age 74), was consistent over time, was not dependent on gender, and exhibited considerable variation among communities.

Abstracting and Indexing↗

PubMed2001

Beta-fibrinogen gene -455G/A polymorphism and coronary heart disease incidence: the Atherosclerosis Risk in Communities (ARIC) Study.

PURPOSE: The -455G/A (HaeIII) polymorphism of the beta-fibrinogen gene influences levels of plasma fibrinogen. We determined whether it influences risk of coronary heart disease. METHODS: We conducted a case-cohort study nested within a prospective investigation, the Atherosclerosis Risk in Communities Study. We accumulated 398 incident coronary heart disease cases over a median of 5.3 years of follow-up and compared their -455G/A status with a random sample of the cohort (n = 498). RESULTS: Plasma fibrinogen was higher (p = 0.04) in AA homozygous participants (341 mg/dL) than in persons carrying the G allele: GA (290 mg/dL), GG (298 mg/dL). However, there was no significant association between -455G/A and incident CHD. CONCLUSIONS: Although a small effect cannot be excluded, -455G/A does not appear to be an important genetic determinant of CHD.

Adenine↗

PubMed2001

Whole and refined grain intake and risk of incident postmenopausal breast cancer (United States).

OBJECTIVE: To assess the relation between whole and refined grain intake and risk of incident postmenopausal breast cancer. Findings from case-control studies of whole and refined grain intake and risk of postmenopausal breast cancer have been inconclusive. METHODS: The Iowa Women's Health Study is a prospective cohort study of women initially 55-69 years old that relates diet and other lifestyle factors to cancer risk. After exclusions a total of 29,119 menopausal women who answered a 1986 baseline and a 1989 follow-up questionnaire were followed for 9 years for incident breast cancer. RESULTS: Compared to women who at baseline rarely ate whole grain foods, women who habitually ate whole grain had a healthier lifestyle, including a higher likelihood of prior screening mammography. The multivariate-adjusted risk of incident breast cancer was 20% higher in women in the highest quintile of whole grain intake, compared to women in the lowest quintile of whole grain intake (95% confidence interval 0.95-1.5; p-value for trend = 0.03). No increase in breast cancer risk was found in women who had not undergone screening mammography before 1989; the apparent increase in risk was therefore likely due to increased use of screening mammography. Refined grain intake was not associated with breast cancer risk. CONCLUSION: Consistent with inverse but not statistically significant associations between whole grain intake and breast cancer in case-control studies, both whole and refined grain intakes are unrelated to risk of postmenopausal breast cancer in these Iowa women.

Aged↗

PubMed2001

Sensitivity and specificity of anthropometrics for the prediction of diabetes in a biracial cohort.

OBJECTIVE: To evaluate the ability of body mass index, waist circumference, waist-to-hip ratio, and combinations of these variables to discriminate individuals who will develop diabetes in adulthood. RESEARCH METHODS AND PROCEDURES: Data were from 45- to 64-year-old men and women who were members of the Atherosclerosis Risk in Communities cohort. The analysis sample consisted of 12,814 African American and white participants who were free of diabetes at baseline. Body mass index, waist circumference, waist-to-hip ratio, and diabetes incidence (defined as one glucose measure > or =126 mg/dL after fasting for at least 8 hours, one nonfasting glucose measure > or =200 mg/dL, and self-report of diabetes or report of taking medication for diabetes). RESULTS: 1515 new cases of diabetes were identified over the 9-year follow-up. Areas under receiver operating characteristic curves ranged from 0.66 to 0.73 for single measures. The curves were smooth, with no indication of a threshold. Waist tended to have the highest receiver operating characteristic statistic in all groups, but differences were small. DISCUSSION: The three anthropometric indices tested were approximately equivalent in their ability to predict diabetes. Sensitivity and specificities differed among ethnic and gender groups.

Anthropometry↗

PubMed2001

Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart Study.

BACKGROUND: Epidemiologic studies suggest that a higher consumption of eicosapentaenoic acid and docosahexaenoic acid is associated with a reduced risk of cardiovascular disease. Studies in humans and animals also reported an inverse association between alpha-linolenic acid and cardiovascular disease morbidity and mortality. OBJECTIVE: We examined the relation between dietary linolenic acid and prevalent coronary artery disease (CAD). DESIGN: We studied 4584 participants with a mean (+/-SD) age of 52.1 +/- 13.7 y in the National Heart, Lung, and Blood Institute Family Heart Study in a cross-sectional design. Participants' diets were assessed with a semiquantitative food-frequency questionnaire. For each sex, we created age- and energy-adjusted quintiles of linolenic acid, and we used logistic regression to estimate prevalent odds ratios for CAD. RESULTS: From the lowest to the highest quintile of linolenic acid, the prevalence odds ratios of CAD were 1.0, 0.77, 0.61, 0.58, and 0.60 for the men (P for trend = 0.012) and 1.0, 0.57, 0.52, 0.30, and 0.42 for the women (P for trend = 0.014) after adjustment for age, linoleic acid, and anthropometric, lifestyle, and metabolic factors. Linoleic acid was also inversely related to the prevalence odds ratios of CAD in the multivariate model (0.60 and 0.61 in the second and third tertiles, respectively) after adjustment for linolenic acid. The combined effect of linoleic and linolenic acids was stronger than the individual effects of either fatty acid. CONCLUSIONS: A higher intake of either linolenic or linoleic acid was inversely related to the prevalence odds ratio of CAD. The 2 fatty acids had synergistic effects on the prevalence odds ratio of CAD.

Coronary Artery Disease↗

PubMed2001

Epidemiologic data on the relationships of caloric intake, energy balance, and weight gain over the life span with longevity and morbidity.

Animal experiments have shown that calorically restricted (CR) animals weigh less and live longer than their ad libitum-fed peers. Are these observations applicable to human beings? This is an important question because the prevalence of obesity in America has increased markedly over recent years. We examine whether there are physiologic effects that occur with CR in humans that could plausibly explain the observed longevity of laboratory animals associated with CR. We also review epidemiologic data from observational and interventional studies on the relationships of caloric intake, energy balance, and weight gain with age-related diseases and longevity. Additionally, data on whether long-term, sustained maintenance of weight loss is feasible, as well as the degree of CR achieved in clinical trials, are summarized. Finally, we provide recommendations regarding further epidemiologic research that will help clarify unanswered questions in these areas.

Energy Intake↗