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Christopher H Schmid

Publications and source records attributed to Christopher H Schmid.

At least 19 recordsLinked to original sources
PubMed2005

Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level.

High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid profile. We tested for a role of interaction between smoking and estrogen receptor alpha gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and LDL particle size. We studied 1727 unrelated subjects, 854 women and 873 men, mean age 51 years (SD 10), from the population-based Framingham Heart Study. After covariate adjustment, women who smoked and had the common ESR1 c.454-397 TT genotype (in 30% of women, T was present on both chromosomes at position 397 prior to the start of exon 2) had >1.7-fold higher levels of small LDL particles than women with the alternative genotypes (P-value for smoking-genotype interaction was 0.001). Similar results were obtained for three other ESR1 variants including c.454-351A > G, in the same linkage disequilibrium block. A similar substantial gender-specific result was also evident with a fifth variant, in a separate linkage disequilibrium block, in exon 4 (P = 0.003). Women who smoked and had specific, common ESR1 genotypes had a substantially higher plasma concentration of atherogenic small LDL particles. Significant results revealed a dose-dependent effect of smoking and were evident in both pre- and postmenopausal women. The reported association has the potential to explain the risks associated with estrogen use in certain women and a recent report of association between an ESR1 haplotype comprised of c.454-397 T and c.454-351 A alleles with increased myocardial infarction and ischaemic heart disease, independent of the standard, established cardiovascular risk factors.

Estrogen Receptor alpha↗
PubMed2005

Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study.

Plasma lipid profile is affected by endogenous estrogen levels and hormone replacement therapy (HRT). As plasma lipid concentrations have a significant heritable basis and the effects of both endogenous estrogen and use of HRT are mediated by estrogen receptors, we sought to investigate the relationships between polymorphisms in estrogen receptor-alpha (ESR1) and plasma lipid and lipoprotein concentrations. We analyzed data from 854 women (mean age 52+/-10 years) from the Framingham Heart Study. A TA repeat in the promoter region, c.30T>C in exon 1, c.454-397T>C, and c.454-351A>G in intron 1, all in linkage disequilibrium (LD), were significantly associated with low-density lipoprotein (LDL) particle size and concentration of small LDL particles. Women with the c.454-397C allele had larger LDL particle size (21.09+/-0.02 nm versus 21.01+/-0.03 nm, p=0.021) concurrent with lower small LDL particle concentration (0.47+/-0.02 mmol/L versus 0.58+/-0.03 mmol/L, p=0.008). Moreover, the TA[L]-c.30C-c.454-397C-c.454-351G haplotype (frequency, 32%) was associated with lower small LDL particle concentrations (-0.06+/-0.03 mmol/L change associated with each copy of this haplotype, p=0.011) when compared to the TA[S]-c.30T-c.454-397T-c.454-351A haplotype (frequency, 46%), where L and S are long and short TA repeats. Our results suggest that common ESR1 polymorphisms have a significant effect on lipoprotein metabolism in women.

Alleles↗
PubMed2005

Proteinuria in South Asian children: prevalence and determinants.

Proteinuria in children is a marker of kidney disease and atherosclerosis, both which are known predictors of cardiovascular mortality. Recent evidence suggests that migrant South Asian populations living in the West may be at higher risk of kidney disease than native Caucasians. However, the determinants of proteinuria in South Asian children have not been explored. Previously, we reported ethnic variation in the prevalence of proteinuria in the adult population of Pakistan. However, it is not known whether ethnic predisposition to proteinuria appears during childhood or whether it is acquired later in life as a result of prolonged exposure to undiagnosed diabetes and hypertension. Analyses were based on a subset of data for 4977 children aged 5 to less than 15 years collected as part of the broad National Health Survey of Pakistan, conducted between 1990 and 1994. Proteinuria was defined as a dipstick positive for protein on a random urine sample. Ethnicity was reported as "mother-tongue", which is specific for each of the five major ethnic subgroups of Pakistan: Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi. The overall prevalence (95% CI) of proteinuria in the children was 3.3% (2.7-3.9%). It was 6.2% in Sindhis, 3.6% in Muhajirs, 2.8% in Punjabis, 2.8% in Baluchis, and 1.0% in Pashtuns (p<0.001). In multivariable analyses, proteinuria was associated with greater height (p=0.007), urban dwelling (p=0.03), lower socioeconomic status (p=0.02), and certain ethnicities (p=0.005). The ethnic variation in proteinuria in South Asian children mirrors variation among ethnic groups in adults. This suggests variations in susceptibility or early exposure to causes of chronic kidney disease, rather than long-term exposure to undiagnosed diabetes or hypertension. Further studies are needed to determine factors in early life that may differentially predispose certain ethnic groups to proteinuria.

Adolescent↗
PubMed2005

Serum creatinine as marker of kidney function in South Asians: a study of reduced GFR in adults in Pakistan.

Migrant populations of South Asian origin have a higher risk for chronic kidney disease than the native whites. Several formulas have been developed to estimate kidney function from serum creatinine concentration. However, none of these has been validated in the South Asian population, which generally has different muscle mass composition than whites. A population-based cross-sectional study was performed on 262 individuals who were aged > or = 40 yr in Karachi, Pakistan. Reduced GFR was defined as creatinine clearance (Ccr) measured in 24-h urine collection of <60 ml/min per 1.73 m2. Creatinine excretion was compared with age- and gender-matched white individuals by comparison of observed versus expected results on the basis of a formula using t test. The agreement among Cockcroft Gault (CG) Ccr and Modification of Diet in Renal Disease (MDRD) Study GFR equations was assessed by regression analyses, and the degree of accuracy of estimated versus measured GFR was determined. Mean (95% confidence interval) creatinine excretion was 1.7 (1.0 to 2.4) mg/kg per d lower than expected for age- and gender-matched white individuals (P < 0.001). The coefficient of determination for measured Ccr on the logarithmic scale was 66.7 and 55.6% for the CG and MDRD Study equations, respectively. The proportion of estimates within 20, 30, and 50% of measured Ccr values was 47.7 versus 32.8% (P < 0.001), 64.9 versus 49.6% (P < 0.001), and 79.4 versus 72.9 (P = 0.07) for CG versus MDRD Study equations, respectively. Lower mean creatinine excretion in these individuals may explain, in part, suboptimal agreement between estimated versus measured GFR. Inclusion of terms for ethnic and racial groups other than white and black might improve the performance of GFR estimating equations.

Adult↗
PubMed2005

Children in South Asia have higher body mass-adjusted blood pressure levels than white children in the United States: a comparative study.

BACKGROUND: Blood pressure during childhood is an established predictor of adult blood pressure, which in turn increases mortality as a result of cardiovascular disease. Adult South Asian populations are particularly predisposed to cardiovascular disease compared with whites, but the prevalence of high blood pressure and determinants of blood pressure in South Asian children have not been explored or compared with those of white children. METHODS AND RESULTS: Analyses were performed on 5641 South Asian children 5 to 14 years old included in the nationally representative National Health Survey of Pakistan (NHSP) (1990-1994) and on 4756 white children 5 to 14 years old included in Third National Health and Nutrition Examination Survey (NHANES III) (1988-1994). Anthropometric measurements were obtained. Blood pressure was measured twice in the seated position with a mercury sphygmomanometer and an appropriate-size cuff. High blood pressure was defined as a systolic or diastolic blood pressure level that was > or =95th percentile of age-, sex-, and height-percentile-specific reference level for the US population. Mean body mass index (BMI)-adjusted blood pressure values were compared among children in 2 data sets by use of linear regression analysis. The overall prevalence (95% CI) of high blood pressure in South Asian children 5 to 14 years old was 12.2% (11.3% to 13.1%): 15.8% (14.5% to 17.1%) in boys and 8.7% (7.6% to 9.8%) in girls. This is in sharp contrast with the predicted 5% prevalence of high blood pressure in children in the United States (P<0.001). The mean BMI-adjusted systolic blood pressure levels (SD) were 100 (11) versus 99 (11) mm Hg (P<0.001), and diastolic blood pressure levels (SD) were 63 (10) versus 52 (12) mm Hg (P<0.001) in NHSP versus NHANES III, respectively. CONCLUSIONS: South Asian children have higher body-mass-adjusted blood pressure levels than white children in the United States. Further studies are needed to determine factors responsible for these differences. Immediate attention is needed to address high blood pressure and its risk factors in native South Asian children.

Adolescent↗
PubMed2005

Long-term effectiveness of weight-loss interventions in adults with pre-diabetes: a review.

OBJECTIVE: To assess the effectiveness of weight-loss and weight-control interventions for adults with pre-diabetes (impaired fasting glucose and impaired glucose tolerance), an important risk factor for the development of type 2 diabetes. METHODS: Computerized searches were conducted of multiple electronic bibliographic databases up to August 2003. Randomized controlled trials in any language were selected that examined weight-loss or weight-control strategies using at least one dietary, physical activity, or behavioral intervention, and with a follow-up interval of a per thousand yen12 months. Effects were combined using a random effects model. RESULTS: Studies were identified, with a total of 5168 participants. Follow-up ranged from 1 to 10 years. Quantitative synthesis was limited by the heterogeneity of populations, settings, and interventions, and by the small number of studies that examined outcomes other than weight. Overall, compared to usual care, four studies with a follow-up of 1 year reduced weight by 2.8 kg (95% confidence interval [CI]=1.0-4.7) (3.3% of baseline body weight) and decreased body mass index by 1.4 kg/m(2) (CI=0.5-2.3). Weight loss at 2 years was 2.7 kg (CI=1.9-3.4) (two studies). Modest improvements were noted in the few studies that examined glycemic control, blood pressure, and lipid concentrations (p >0.05). The incidence of diabetes was significantly lower in the intervention groups versus the controls in three of five studies examining this outcome at 3 to 6 years follow-up. CONCLUSIONS: Overall, weight-loss strategies using dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with pre-diabetes, and a significant decrease in diabetes incidence. Further work is needed on the long-term effects of these interventions on morbidity and mortality and on how to implement these interventions in the community setting.

Adult↗
PubMed2005

Association of estrogen receptor beta gene polymorphisms with left ventricular mass and wall thickness in women.

BACKGROUND: Left ventricular (LV) hypertrophy is a significant risk factor for cardiovascular disease. Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure. METHODS: We studied 1249 unrelated individuals, 547 men and 702 women (mean age 59 years) from the Framingham Heart Study. Eight single nucleotide polymorphisms in the genes for estrogen receptor alpha and estrogen receptor beta (ESR2) were tested for association with 5 LV measures: LV mass (LVM), LV wall thickness (LVWT), LV internal diameter at end-diastole and end-systole, and fractional shortening. Sex-specific multiple regression analyses were performed adjusting for age, weight, height, systolic and diastolic blood pressure, hypertension treatment, diabetes, and in women, menopausal status. RESULTS: In men, there was no evidence of association between the estrogen pathway polymorphisms tested and LV structure or function. In women, however, two polymorphisms, ESR2 rs1256031 and ESR2 rs1256059, in linkage disequilibrium with one another, were associated with LVM and LVWT (P = .0007 to .03); the association was most pronounced in those women with hypertension (P = .0006 to .01). The association did not appear to be explained by variation in blood pressure, plasma lipoprotein levels, or hyperglycemia. CONCLUSIONS: The ESR2 polymorphisms are associated with LV structural differences in women with hypertension in a community-based population. These data are consistent with the hypothesis that genetic factors may mediate part of the observed sex-based differences in LV structure and remodeling.

Aged↗
PubMed2005

Dietitian involvement in the neonatal intensive care unit: more is better.

OBJECTIVE: Describe the level of registered dietitian (RD) involvement in neonatal intensive care units (NICUs) and associations with NICU nutrition practices. DESIGN: Questionnaires were mailed to 820 NICUs in the United States with two follow-up mailings to nonresponders. Abbreviated phone surveys were conducted with a random sample of 10% of nonresponders. A nutrition care score was devised based on a sum of 10 survey questions (range 0 to 10) to summarize the intensity of reported practices. SUBJECTS/SETTING: Directors of NICUs in the United States and RDs associated with them. STATISTICAL ANALYSES: Chi2, analysis of variance, Bonferroni and Duncan multiple range tests, regression. RESULTS: Respondents from 417 (54%) of the 772 NICUs eligible for the study provided completed questionnaires. Among NICUs responding, 76% involved RDs in care (41% employed full- or part-time RDs, 35% employed consult RDs), and 24% had no RD. NICUs with full- or part-time RDs provided fewer kilocalories and more protein parenterally, and more kilocalories and protein enterally. NICUs with less RD involvement were more likely to provide full-term infant feedings (eg, unfortified breast milk, full-term formula) to very-low-birth-weight infants. Mean nutrition care score varied with RD involvement from 4.6+/-1.7 (mean+/-standard deviation) for NICUs with a consult RD and 4.7+/-1.4 for NICUs employing no RD to 5.6+/-1.7 for NICUs with a full- or part-time RD (overall P<.001). CONCLUSIONS: More involvement of RDs in NICUs increased the intensity of important aspects of nutrition care that may improve outcomes of very-low-birth-weight infants in NICUs. These findings highlight the importance of RDs as NICU team members.

Analysis of Variance↗
PubMed2005

In an empirical evaluation of the funnel plot, researchers could not visually identify publication bias.

BACKGROUND AND OBJECTIVE: Publication bias and related biases can lead to overly optimistic conclusions in systematic reviews. The funnel plot, which is frequently used to detect such biases, has not yet been subjected to empirical evaluation as a visual tool. We sought to determine whether researchers can correctly identify publication bias from visual inspection of funnel plots in typical-size systematic reviews. METHODS: A questionnaire with funnel plots containing 10 studies each (the median number in medical meta-analyses) was completed by 41 medical researchers, including clinical research fellows in a meta-analysis class, faculty in clinical care research, and experienced systematic reviewers. RESULTS: On average, participants correctly identified 52.5% (95% CI 50.6-54.4%) of the plots as being affected or unaffected by publication bias. The weighted mean percent correct, which adjusted for the fact that asymmetric plots are more likely to occur in the presence of publication bias, was also low (48.3 to 62.8%, depending on the presence or absence of publication bias and heterogeneous study effects). CONCLUSION: Researchers who assess for publication bias using the funnel plot may be misled by its shape. Authors and readers of systematic reviews need to be aware of the limitations of the funnel plot.

Humans↗
PubMed2005

Variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in the Framingham Heart Study.

OBJECTIVE: To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women. DESIGN: In 1780 unrelated members of the community-based Framingham Heart Study offspring cohort, systolic blood pressure and diastolic blood pressure were measured over a total of six examination cycles encompassing 24 years of follow-up. Multivariate regression analyses were used to assess the relation between untreated cross-sectional and longitudinal blood pressure and polymorphisms at the estrogen receptor-alpha (ESR1), estrogen receptor-beta (ESR2), aromatase (CYP19A1), and nuclear receptor coactivator 1 (NCOA1) genes after adjustment for common risk factors. RESULTS: In men, systolic blood pressure and pulse pressure (systolic blood pressure minus diastolic blood pressure) were associated with two polymorphisms in ESR1, while pulse pressure was also associated with variations in NCOA1 and CYP19A1. Polymorphisms in ESR1, CYP19A1, and NCOA1 were associated with diastolic blood pressure in women. CONCLUSIONS: Although the underlying relations between genes involved in estrogen action and hypertension remain to be completely understood, our findings provide suggestive evidence of gender-specific contributions of estrogen-related genes to blood pressure variation. As no correction for multiple testing was performed in the analyses, we view these results as suggestive and not definitive. Further studies are warranted to confirm these results using a comprehensive set of polymorphisms in order to shed more light on the involvement of estrogen in blood pressure regulation.

Aromatase↗
PubMed2005

The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease.

BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors (controls) on kidney disease progression in patients with PKD. METHODS: We analyzed a database of 11 randomized controlled trials including 1860 patients with nondiabetic kidney disease. We compared randomized groups for the decline in urine protein excretion and kidney disease progression (combined outcome of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine protein excretion in both models. RESULTS: Eight studies included a total of 142 subjects with PKD: 68 (48%) were randomized to ACE inhibitors and 74 (52%) were randomized to the control. Baseline mean (SD) urine protein excretion was 0.92 (1.40) g/day: 1.08 (1.50) g/day in the ACE inhibitor and 0.76 (1.28) g/day in the control group. During a mean follow-up of 2.3 years, mean (SD) urine protein excretion declined by 0.33 (1.11) g/day in the ACE inhibitor group and increased by 0.19 (0.88) g/day in the control group (P < 0.001). Kidney disease progression occurred in 50 patients: 20 patients (29%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P < 0.001 and P= 0.03, respectively). CONCLUSION: As in other causes of non-diabetic kidney disease, antihypertensive regimens with ACE inhibitors are more effective in lowering urine protein excretion in patients with advanced PKD compared to regimens without ACE inhibitors, and this benefit is greater in patients with higher levels of baseline urine protein excretion. The effect of ACE inhibitors to slow kidney disease progression in PKD is inconclusive.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis.

BACKGROUND: Most persons with type 2 diabetes are overweight, and obesity worsens the metabolic and physiologic abnormalities associated with diabetes. Our objective was to assess the effectiveness of lifestyle and behavioral weight loss and weight control interventions in adults with type 2 diabetes. METHODS: Studies were obtained from searches of multiple electronic bibliographic databases, supplemented with hand searches of selected journals and consultation with experts in obesity research. Studies were included if they were published or unpublished randomized controlled trials in any language that examined weight loss or weight control strategies using one or more dietary, physical activity, or behavioral interventions, with a follow-up interval of at least 12 months. Effects were combined using a random-effects model. RESULTS: The 22 studies of weight loss interventions identified yielded a total of 4659 participants with a follow-up of 1 to 5 years. The pooled weight loss for any intervention in comparison with usual care among 585 subjects was 1.7 kg (95% confidence interval [CI]: 0.3 to 3.2 kg), or 3.1% of baseline body weight among 511 subjects. Among 126 persons who underwent a physical activity and behavioral intervention, those who also received a very low-calorie diet lost 3.0 kg (95% CI: -0.5 to 6.4 kg), or 1.6% of baseline body weight, more than persons who received a low-calorie diet. Among 53 persons who received identical dietary and behavioral interventions, those who received a more intense physical activity intervention lost 3.9 kg (95% CI: -1.9 to 9.7 kg), or 3.6% of baseline body weight, more than those who received a less intense or no physical activity intervention. Comparison groups often achieved substantial weight loss (up to 10.0 kg), minimizing between-group differences. Changes in glycated hemoglobin level generally corresponded to changes in weight and were not substantial when between-group differences were examined. CONCLUSION: Weight loss strategies involving dietary, physical activity, or behavioral interventions were associated with small between-group improvements in weight. These results were minimized by weight loss in the comparison group, however, and examination of individual study arms revealed that multicomponent interventions, including very low-calorie diets or low-calorie diets, may hold promise for achieving weight loss in adults with type 2 diabetes.

Behavior Therapy↗
PubMed2004

Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND: Obesity is closely related to type 2 diabetes mellitus, and weight reduction is an important part of the care delivered to obese persons with diabetes. The objective of this review was to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. METHODS: A systematic review of the literature was performed, and studies were included if pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished studies with any design were included. A random effects model was used to combine outcomes from randomized controlled trials. RESULTS: Sufficient data for the meta-analysis were available for fluoxetine, orlistat, and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2231 patients. Pharmacotherapy produced modest reductions in weight for fluoxetine (3.4 kg [95% confidence interval (CI), 1.7-5.2 kg] at 8-16 weeks of follow-up; 5.1 kg [95% CI, 3.3-6.9 kg] at 24-30 weeks; and 5.8 kg [ 95% CI, 0.8-10.8 kg] at 52 weeks); orlistat (2.6 kg [95% CI, 2.1-3.2 kg] [2.6% loss] at 52 weeks); and sibutramine (4.5 kg [95% CI, 1.8-7.2 kg] [3.3% loss] at up to 26 weeks). Glycated hemoglobin was also modestly reduced: fluoxetine (1.0% [95% CI, 0.4%-1.5%] at 8-16 weeks; 1.0% [95% 0.6%-1.4%] at 24-30 weeks; and 1.8% [95% CI, -0.2%-3.8%] at 52 weeks); orlistat (0.4% [95% CI, 0.3%-0.5%]); and sibutramine (0.7% [95% CI, -0.5%-1.9%]). Gastrointestinal adverse effects were common with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine. CONCLUSIONS: Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 26 to 52 weeks. However, the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear. Interventions that combine pharmacologic therapy with intensive behavioral interventions may be more effective but need additional research.

Adult↗
PubMed2004

Meta-regression detected associations between heterogeneous treatment effects and study-level, but not patient-level, factors.

OBJECTIVE: Two investigations evaluate Bayesian meta-regression for detecting treatment interactions. STUDY DESIGN AND SETTING: The first compares analyses of aggregate and individual patient data on 1,860 subjects from 11 trials testing angiotensin converting enzyme (ACE) inhibitors for nondiabetic kidney disease. The second explores meta-regression for detecting treatment interaction on 671 covariates, including the baseline risk, from 232 meta-analyses of binary outcomes compiled from the Cochrane Collaboration and the medical literature. RESULTS: In the ACE inhibitor study, treatment effects were homogeneous so meta-regression identified no interactions. Analysis of individual patient data using a multilevel model, however, discovered that treatment reduced glomerular filtration rate (GFR) more among patients with higher baseline proteinuria. The second investigation found meta-regression most effective for detecting treatment interactions with study-level factors in meta-analyses with >10 studies, heterogeneous treatment effects, or significant overall treatment effects. Under all three conditions, 46% of meta-regressions produced strong interactions (posterior probability >0.995) compared with 6% otherwise. Baseline risk was associated with the odds ratio in 6% of meta-analyses, half the rate found using maximum likelihood. CONCLUSION: Meta-regression can detect interactions of treatment with study-level factors when treatment effects are heterogeneous. Individual patient data are needed for patient-level factors and homogeneous effects.

Adult↗
PubMed2003

Association between estrogen receptor alpha gene variation and cardiovascular disease.

CONTEXT: Estrogen and related hormone therapies activate estrogen receptors, which in turn regulate genes for several cardiovascular disease (CVD) risk factors. Relatively little is known, however, about the impact of genetic variation in estrogen receptor alpha (ESR1) on CVD risk. OBJECTIVE: To investigate whether the ESR1 c.454-397T>C polymorphism is associated with CVD risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 1739 unrelated men and women from the population-based offspring cohort of the Framingham Heart Study, who were followed up from 1971 to 1998. MAIN OUTCOME MEASURES: Total atherosclerotic CVD events, defined as recognized or unrecognized myocardial infarction (MI), angina pectoris, coronary insufficiency, intermittent claudication, coronary heart disease death, or atherothrombotic stroke (n = 178); major atherosclerotic CVD, defined as recognized acute MI, coronary insufficiency, coronary heart disease death, or atherothrombotic stroke (n = 83); and recognized acute MI (n = 59). RESULTS: Twenty percent of participants (n = 352) were homozygous for the ESR1 c.454-397C allele. After adjustment for covariates (age, sex, body mass index, hypertension, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and cigarette smoking), the CC genotype was significantly associated with major atherosclerotic CVD, with an odds ratio of 2.0 (95% confidence interval [CI], 1.3-3.2; P =.004) compared with individuals with the CT or TT genotypes. Participants with the CC genotype had 3.0-fold greater odds of MI (95% CI, 1.7-5.2; P<.001) compared with those with the CT or TT genotype. The results remained significant when analyses were restricted to men; too few women had events to study them separately. CONCLUSIONS: Individuals with the common ESR1 c.454-397CC genotype have a substantial increase in risk of MI. Whether ESR1 c.454-397T>C is causally related to MI risk or in linkage disequilibrium with 1 or more causal variants remains to be determined. These findings support the importance of estrogen receptors in CVD susceptibility, especially in men. Estrogen receptor variation also has potential to explain recent conflicting data regarding the effects of hormone therapy on CVD susceptibility in women.

Cardiovascular Diseases↗
PubMed2003

Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease. PURPOSE: To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during antihypertensive therapy with and without ACE inhibitors. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease. STUDY SELECTION: MEDLINE database search for English-language studies published between 1977 and 1999. DATA EXTRACTION: Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22 610 patient visits. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P < 0.006). CONCLUSION: Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.

Angiotensin-Converting Enzyme Inhibitors↗