Biomedical subjects

Gerardo Heiss

Publications and source records attributed to Gerardo Heiss.

At least 19 recordsLinked to original sources

PubMed2007

Early-life and adult socioeconomic status and inflammatory risk markers in adulthood.

BACKGROUND: Associations between childhood and adult socioeconomic status (SES) and adult levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, white blood cell count [WBC], and von Willebrand factor [vWF]) were examined in the Atherosclerosis Risk in Communities (ARIC) Study cohort. METHODS: A total of 12,681 white and African-American participants provided information on SES (via education and social class) and place of residence in childhood and adulthood. Residences were linked to census data for neighborhood SES information. Multiple imputation was used to impute missing data. Hierarchical and linear regression were used to estimate the effects of SES and possible mediation by adult cardiovascular disease (CVD) risk factors. FINDINGS: Low childhood social class and education were associated with elevated levels of CRP, fibrinogen, WBC, and vWF (increments of 17%, 2%, 4% and 3% for lowest versus highest education in childhood, respectively) among whites. Findings were less consistent among African-Americans. Adult SES was more strongly associated with inflammation than childhood SES. Individual-level SES measures were more consistently associated with inflammation than neighborhood-level measures. Fibrinogen and WBC showed the most consistent associations with SES; the largest changes in inflammation by SES were observed for CRP. Covariate adjustment strongly attenuated these associations. Mediation of the SES-inflammation associations by BMI, smoking and HDL cholesterol (HDL-C) are suggested by these data. CONCLUSION: Low individual- and neighborhood-level SES in childhood and adulthood are associated with modest increments in adult inflammatory burden. These associations may operate through the influence of low SES on traditional CVD risk factors, especially BMI, smoking and HDL-C.

Black or African American↗

PubMed2007

The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001.

BACKGROUND: Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans. METHODS: The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987-89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models. RESULTS: Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI<0.90) was 2.81 (1.77-4.45) for men and 2.05 (1.20-3.53) for women. In African Americans, the HR for men was 4.86 (2.76-8.47) and for women was 2.34 (1.26-4.35). The CHD risk increased exponentially with decreasing ABI as a continuous function, and continued to decline at ABI values > 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17-34%) in white men, by 20% (8-33%) in white women, by 34% (19-50%) in African American men, and by 32% (17-50%) in African American women. CONCLUSION: African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors.

Black or African American↗

PubMed2007

Genotype-by-sex interaction on fasting insulin concentration: the HyperGEN study.

Recent studies have demonstrated the importance of sex effects on the underlying genetic architecture of insulin-related traits. To explore sex-specific genetic effects on fasting insulin, we tested for genotype-by-sex interaction and conducted linkage analysis of fasting insulin in Hypertension Genetic Epidemiology Network families. Hypertensive siblings and their first-degree relatives were recruited from five field centers. We performed a genome scan for quantitative trait loci influencing fasting insulin among 1,505 European Americans and 1,616 African Americans without diabetes. Sex-stratified linear regression models, adjusted for race, center, and age, were explored. The Mammalian Genotyping Service typed 391 microsatellite markers, spaced roughly 9 cM. Variance component linkage analysis was performed in SOLAR using ethnic-specific marker allele frequencies and multipoint IBDs calculated in MERLIN. We detected a quantitative trait locus influencing fasting insulin in female subjects (logarithm of odds [LOD] = 3.4) on chromosome 2 at 95 cM (between GATA69E12 and GATA71G04) but not in male subjects (LOD = 0.0, P for interaction = 0.007). This sex-specific signal at 2p13.2 was detected in both European-American (LOD = 2.1) and African-American (LOD = 1.2) female subjects. Our findings overlap with several other linkage reports of insulin-related traits and demonstrate the importance of considering complex context-dependent interactions in the search for insulin-related genes.

Alcohol Drinking↗

PubMed2006

Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort).

The clinical relevance of ventricular premature complexes (VPCs) in apparently healthy patients is not clear and is typically not considered when evaluating risk. We conducted a prospective longitudinal study of the population-based Atherosclerosis Risk In Communities (ARIC) study of 15,070 Caucasians and African-Americans, 45 to 64 years of age, to assess the risks of coronary heart disease (CHD) events and mortality associated with VPCs among participants with and without prevalent CHD at baseline. VPCs on a single 2-minute electrocardiogram were identified in 940 participants (6.2%). After a follow-up of >10 years, 1,762 participants died, with 366 deaths related to CHD, and 1,736 had cardiac events. The percentage of participants with CHD mortality was >3 times greater for those with VPCs compared with those without VPCs. After controlling for cardiovascular risk factors and therapy with proportional hazards regression, participants with VPCs were >2 times as likely to die due to CHD than were those without VPCs. Increased risk was found for participants with and without baseline CHD. In conclusion, a clinical finding of VPCs on electrocardiography of even apparently healthy patients may warrant a heightened awareness of and attention to cardiovascular risk assessment and management.

Coronary Disease↗

PubMed2006

Cumulative socioeconomic status across the life course and subclinical atherosclerosis.

PURPOSE: The purpose of this study is to investigate the relationship between individual-level and neighborhood-level socioeconomic status (SES) across the life course and subclinical atherosclerosis. METHODS: Participants from the Atherosclerosis Risk in Communities Study (n=12,332) were queried about individual-level SES and residential addresses across the life course. Individual-level measures were scored and summed to obtain a summary score (I-CumSES), whereas residential addresses were geocoded and linked to census data to obtain a summary neighborhood z score (N-CumSES) to evaluate the association of SES with intima-media thickness (IMT) and peripheral arterial disease (PAD). RESULTS: A 1-SD lower I-CumSES was associated with greater mean IMT in each race-sex group and greater odds of PAD in white men (odds ratio [OR], 1.28; 95% confidence interval [CI], 0.99-1.64), white women (OR, 1.18; 95% CI, 1.02-1.36), and black women (OR, 1.33; 95% CI, 1.00-1.76). Compared with the highest tertile of N-CumSES, the lowest tertile was associated with greater mean IMT among whites, but was not associated with PAD for whites or blacks. When I-CumSES and N-CumSES were considered simultaneously, associations remained for only I-CumSES and were attenuated after adjustment for cardiovascular disease (CVD) risk factors. CONCLUSIONS: Lower cumulative individual-level SES across the life course was associated with a greater burden of subclinical atherosclerosis, and this association was mediated in part by CVD risk factors.

Atherosclerosis↗

PubMed2006

Coffee and sweetened beverage consumption and the risk of type 2 diabetes mellitus: the atherosclerosis risk in communities study.

The authors analyzed data from a prospective, community-based cohort to assess the risk of incident type 2 diabetes mellitus associated with coffee and sweetened beverage consumption. They included 12,204 nondiabetic, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1999). Consumption of each beverage was assessed by food frequency questionnaire and classified into categories of cups per day. They found an inverse association, after adjusting for potential confounders, between increased coffee consumption and risk of type 2 diabetes mellitus in men (for > or =4 cups (> or =0.95 liter)/day compared with almost never: hazard ratio = 0.77, p(trend) = 0.02) with no significant association in women (hazard ratio = 0.89, p(trend) = 0.32) using a combination of self-report of physician-diagnosed diabetes, diabetes treatment, and a fasting or nonfasting blood glucose test. When self-reported diabetes or diabetes treatment alone was used, a stronger and significant inverse association was seen in men and women. Sweetened beverage consumption (men: hazard ratio = 1.03, p(trend) = 0.94; women: hazard ratio = 1.01, p(trend) = 0.58) showed no consistent association with the incidence of type 2 diabetes mellitus. In summary, increased coffee consumption was significantly associated with a decreased risk of diagnosed type 2 diabetes mellitus in community-based US adults.

Beverages↗

PubMed2006

Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. METHODS AND RESULTS: We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987-1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0; 95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6). CONCLUSIONS: OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Age Factors↗

PubMed2006

Accuracy of commercial geocoding: assessment and implications.

BACKGROUND: Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI. RESULTS: Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean rho [meters]: 1809; 748; 704; 228). Mean rho was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and among-vendor heteroscedasticity of rho, differences in mean rho were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) p(interaction) < 10(-4), i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure--distance to the nearest highway--increased with mean rho and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null. CONCLUSION: Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects.

Journal Article↗

PubMed2006

An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study.

BACKGROUND: There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models. METHODS: Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15,792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors. RESULTS: The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A(2), vitamin B(6), interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011). CONCLUSIONS: Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Influence of saturated fat and linolenic acid on the association between intake of dairy products and blood pressure.

Data on the association between dairy consumption and blood pressure have been inconsistent. We sought to examine the relation between dairy consumption and prevalent hypertension (HTN) among 4797 participants of the National Heart, Lung, and Blood Institute Family Heart Study. We used generalized estimating equations to estimate prevalence odds ratios of HTN across categories of dairy consumption. From the lowest to the highest sex-, age-, and energy-adjusted quartile of dairy consumption, there was an inverse association between dairy intake and prevalent HTN: odds ratios (95% CIs) were 1.0 (reference), 0.82 (0.64 to 1.05), 0.68 (0.53 to 0.89), and 0.62 (0.45 to 0.84), respectively, in a model adjusting for age, sex, energy intake, field center, body mass index, dietary linolenic acid, saturated and monounsaturated fat, sodium intake, potassium, caffeine, fiber, and fruits and vegetables (P for trend = 0.002). This association was independent of calcium intake and was mainly observed among subjects consuming fewer calories from saturated fat (P for interaction = 0.014). Dairy consumption was inversely associated with systolic (P for trend = 0.003) but not diastolic (P for trend = 0.09) blood pressure. Although subjects consuming > or = 2 servings per day of dairy products and higher total linolenic acid had the lowest prevalence odds of HTN, there was no evidence for interaction between linolenic acid and dairy consumption on HTN (P for interaction = 0.65). In conclusion, our data indicate an inverse association between dairy consumption and prevalent HTN that was independent of dietary calcium, mainly among individuals consuming less saturated fat. This suggests that consumption of low-fat dairy products might be more beneficial for preventing HTN.

Adult↗

PubMed2006

Apolipoprotein E polymorphisms predict low density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants.

Elevated levels of low density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease, and recent advancements have provided evidence that carotid artery intima-media thickness (IMT) is associated with increased occurrence of cardiovascular events. Apolipoprotein E (ApoE) has been widely studied in regard to its role in lipid transport and metabolism, but the role that ApoE genetic variation plays in relation to carotid artery IMT and risk of incident coronary heart disease remains a subject of debate. In 1987-2001, the authors examined the effect of each ApoE allele (epsilon2, epsilon3, epsilon4) on LDL cholesterol and carotid IMT, as well as the association with coronary heart disease risk, in 12,491 participants of the US Atherosclerosis Risk in Communities Study. ApoE epsilon2, epsilon3, and epsilon4 allele frequencies were determined, respectively, in Whites (0.08, 0.77, 0.15) and African Americans (0.11, 0.67, 0.22). These alleles did not predict incident coronary heart disease in either racial group. The ApoE epsilon2 allele was associated with lower LDL cholesterol and the epsilon4 allele with higher LDL cholesterol in both Whites and African Americans. The ApoE epsilon2 and epsilon4 alleles were associated with carotid IMT measures in both racial groups, but, after adjusting for lipid parameters, only the epsilon4 allele was associated with carotid IMT measures in African Americans.

Apolipoproteins E↗

PubMed2006

Association of coronary artery calcified plaque with clinical coronary heart disease in the National Heart, Lung, and Blood Institute's Family Heart Study.

The presence of calcified coronary artery plaque has shown variable association with clinical coronary heart disease (CHD), particularly after adjustment for other risk factors. From 2002 to 2004, as part of the National Heart, Lung, and Blood Institute's Family Heart Study, coronary artery calcium (CAC) scans by 4-slice multidetector computed tomography were performed in 3,359 subjects, including 389 with clinically diagnosed CHD. Among these was a cohort of 2,254 patients who had been asymptomatic at an initial examination 7 to 9 years previously (1994 to 1996), with 111 who had developed newly diagnosed, nonfatal CHD since the initial examination. In cross-sectional analyses, we examined associations between CAC and CHD in the entire group and in the subgroup seen at the initial examination. In the 2 sets of analyses, odds ratios for CHD ranged from approximately 4 in those with CAC scores of 100 to 199 (p <0.01) to >20 in those with CAC scores >/=1,000 (p <0.0001) compared with those with no measurable CAC. This steep gradient of risk persisted after adjustment for risk factors. A quantitative CHD family history score was significantly associated with CHD even after adjusting for all standard risk factors and including CAC in the model. In conclusion, CAC was strongly associated with CHD even after adjustment for standard risk factors and family history contributed independently to CHD risk.

Adult↗

PubMed2006

Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study.

Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the vasculature and regulates endothelial function. We sought to determine whether genetic variation in soluble epoxide hydrolase (EPHX2) was associated with the risk of CHD. We genotyped 2,065 Atherosclerosis Risk in Communities study participants (1,085 incident CHD cases, 980 non-cases) for 10 previously identified polymorphisms in EPHX2. Using a case-cohort design, associations between incident CHD risk and both non-synonymous EPHX2 polymorphisms and phase-reconstructed haplotypes were evaluated using proportional hazards regression. Individuals carrying the K55R polymorphism variant allele demonstrated higher apparent soluble epoxide hydrolase activity in vivo. Presence of the K55R variant allele was significantly more common among Caucasian CHD cases when compared with non-cases (20.8% versus 15.3%, respectively, P=0.012), and was associated with significantly higher risk of incident CHD (adjusted hazard rate ratio 1.45, 95% confidence interval 1.05-2.01, P=0.026). A significant association between the K55R variant allele and risk of CHD was not observed in African-Americans. The distribution of reconstructed haplotypes were significantly different in Caucasian cases when compared with non-cases (P=0.021). Significant differences in haplotype distribution were not observed in African-Americans (P=0.315). Genetic variation in EPHX2 was significantly associated with risk of incident CHD in Caucasians, implicating EPHX2 as a potential cardiovascular disease-susceptibility gene.

Black or African American↗

PubMed2006

Evidence of QTL on 15q21 for high-density lipoprotein cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study (NHLBI FHS).

A genome-wide linkage scan was conducted to identify regions potentially having quantitative trait loci (QTLs) influencing high-density lipoprotein (HDL) cholesterol. We found suggestive evidence of a QTL (lod score (LOD)=1.75, p=0.00224, and q=0.07649) influencing the variation of plasma levels of age- and sex-adjusted HDL-cholesterol on chromosome 15q21 at marker D15S659 in the NHLBI FHS data. Owing to the perturbations to lipid profiles associated with diabetes, the analysis was repeated excluding diabetic subjects from the sample. The lod score increased from 1.75 to 2.71 (p=0.00021, q=0.05392) at the same chromosome 15 location, despite the reduction in sample size. This finding indicates that the inclusion of diabetic subjects in the analysis may confound the presence of a QTL for HDL-cholesterol on 15q21. Because of the known effects of important covariates such as metabolic variables and lifestyle habits that may interact with a putative QTL, we also analyzed HDL-cholesterol with a progressive adjustment. When body mass index, smoking, and habitual alcohol intake were added to age- and sex-adjustment, we found strong evidence for linkage in the complete sample (LOD=4.77, p=0.0000013, and q=0.00016) as well as in the non-diabetic sub-sample (LOD=4.52, p=0.0000025, and q=0.00026) on chromosome 15q21 (between D15S659 and D15S195 markers). These results suggest that there are multiple pathways and factors involving genetic and environmental effects influencing HDL-cholesterol levels, and by taking some of these known factors into account, we obtained strong evidence of a QTL influencing HDL-cholesterol levels. While this putative QTL may also have an effect in diabetes, our data suggest a more pronounced role in non-diabetics. A prominent candidate gene residing within the linkage region on 15q21 is hepatic lipase (HL), which has a major role in lipoprotein metabolism.

Adult↗

PubMed2006

The reliability of the ankle-brachial index in the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS).

BACKGROUND: A low ankle-brachial index (ABI) is associated with increased risk of coronary heart disease, stroke, and death. Regression model parameter estimates may be biased due to measurement error when the ABI is included as a predictor in regression models, but may be corrected if the reliability coefficient, R, is known. The R for the ABI computed from DINAMAP readings of the ankle and brachial SBP is not known. METHODS: A total of 119 participants in both the Atherosclerosis Risk in Communities (ARIC) study and the NHLBI Family Heart Study (FHS) had repeat ABIs taken within 1 year, using a common protocol, automated oscillometric blood pressure measurement devices, and technician pool. RESULTS: The estimated reliability coefficient for the ankle systolic blood pressure (SBP) was 0.68 (95% CI: 0.57, 0.77) and for the brachial SBP was 0.74 (95% CI: 0.62, 0.83). The reliability for the ABI based on single ankle and arm SBPs was 0.61 (95% CI: 0.50, 0.70) and the reliability of the ABI computed as the ratio of the average of two ankle SBPs to two arm SBPs was estimated from simulated data as 0.70. CONCLUSION: These reliability estimates may be used to obtain unbiased parameter estimates if the ABI is included in regression models. Our results suggest the need for repeated measures of the ABI in clinical practice, preferably within visits and also over time, before diagnosing peripheral artery disease and before making therapeutic decisions.

Ankle↗

PubMed2006

Calcium plus vitamin D supplementation and the risk of fractures.

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

Aged↗

PubMed2006

Calcium plus vitamin D supplementation and the risk of colorectal cancer.

BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

Adenocarcinoma↗

PubMed2006

Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

CONTEXT: The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial. OBJECTIVE: To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence. DESIGN AND SETTING: A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005. PARTICIPANTS: A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled. INTERVENTIONS: Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes. MAIN OUTCOME MEASURE: Invasive breast cancer incidence. RESULTS: Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor. CONCLUSIONS: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.

Aged↗