Limited recovery of ß-cell function after gastric bypass despite clinical diabetes remission.

The mechanisms responsible for the remarkable remission of type 2 diabetes after Roux-en-Y gastric bypass (RYGBP) are still puzzling. To elucidate the role of the gut, we compared ß-cell function assessed during an oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose clamp (iso-IVGC) in: 1) 16 severely obese patients with type 2 diabetes, up to 3 years post-RYGBP; 2) 11 severely obese normal glucose-tolerant control subjects; and 3) 7 lean control subjects. Diabetes remission was observed after RYGBP. ß-Cell function during the OGTT, significantly blunted prior to RYGBP, normalized to levels of both control groups after RYGBP. In contrast, during the iso-IVGC, ß-cell function improved minimally and remained significantly impaired compared with lean control subjects up to 3 years post-RYGBP. Presurgery, ß-cell function, weight loss, and glucagon-like peptide 1 response were all predictors of postsurgery ß-cell function, although weight loss appeared to be the strongest predictor. These data show that ß-cell dysfunction persists after RYGBP, even in patients in clinical diabetes remission. This impairment can be rescued by oral glucose stimulation, suggesting that RYGBP leads to an important gastrointestinal effect, critical for improved ß-cell function after surgery.

The relation of blood pressure to coronary heart mortality in different age groups varies by ethnicity.

BACKGROUND: The relative importance of pulse pressure, mean arterial pressure, systolic blood pressure (SBP), and diastolic blood pressure (DBP) as predictors of coronary heart disease (CHD) have been shown to change with aging in individuals of white ethnicity, but few published data exist for those of African American ethnicity. METHODS: To assess the role of ethnicity in this relationship we compared the association of BP indices to CHD mortality (from a pooled database of eight prospective cohorts, n = 29829, follow-up 13.8 +/- 7.9 years, 1912 events) in the four age groups (30 to 39, 40 to 49, 50 to 59, and > or = 60 years) by the decrease in the -2 log likelihood in Cox regression analyses of subjects who were not receiving antihypertensive drug therapy at baseline. RESULTS: All BP indices were significant (P < .05) for all age groups in models containing a single BP index. In white subjects, the best predictor of CHD mortality was DBP for persons 30 to 39 years of age, whereas SBP was the best predictor for persons 40 to 49, 50 to 59 and > or = 60 years of age. In African American subjects, SBP was the best predictor in all age groups. When considered jointly, DBP, but not SBP, was significantly associated with CHD mortality in white subjects 30 to 39 years of age. Only SBP was significant in white subjects 40 to 49, 50 to 59, and > or = 60 years of age. In African Americans, SBP, but not DBP, was associated with CHD mortality in all four age groups when both were in the model. CONCLUSION: In African American subjects, SBP was found to be a better predictor of CHD mortality than DBP or pulse pressure. In white subjects, there was a shift in importance from DBP to SBP as predictors of CHD mortality from the 30 to 39-year age group to the older groups.

Waist circumference predicts cardiometabolic and global Framingham risk among women screened during National Woman's Heart Day.

PURPOSE: To evaluate the cardiometabolic risk profiles of 6938 women (mean age 49.2 +/- 14.6 years) attending the 2005 Sister to Sister: Everyone Has a Heart Foundation free public health standardized cardiovascular disease (CVD) risk factor screening events in 12 cities across the United States by race/ethnicity and waist circumference. MAIN FINDINGS: Among women without a history of CVD or diabetes (n = 6327), 90% were found to have at least one major modifiable CVD risk factor, with one-third of women having three or more major risk factors. Nearly half of all women with elevated total cholesterol (> or = 200 mg/dL) or low high-density lipoprotein (HDL)-cholesterol (< 50 mg/dL) did not report a known history of abnormal cholesterol. Among women with no history of hypertension, 16% had a blood pressure > or = 140/90 mm Hg. Unrecognized diabetes and glucose intolerance were striking among fasting women (n = 1218; 9% had a blood glucose > or = 126 mg/dL and 43% had a blood glucose > or = 100 mg/dL). In adjusted logistic regression models, women with a waist circumference > or = 35 inches were more likely to have blood pressure > or = 140/90 (OR = 1.9, p < 0.0001), total cholesterol > or = 200 mg/dL (OR = 1.2, p = 0.006), HDL-cholesterol < 50 mg/dL (OR = 2.5, p < 0.0001), fasting glucose > or = 100 mg/dL (OR = 2.0, p < 0.0001), and Framingham global risk score > or = 10%, CVD or diabetes (OR = 2.0, p < 0.0001). Waist circumference was significantly correlated with Framingham global risk (r = 0.24, p < 0.001) and number of risk factors (r = 0.24, p < 0.0001). Increased clustering of risk factors was predictive of waist size > or = 35 inches vs. < 35 inches in logistic models (p for trend > 0.0001). Among a subsample of women who underwent standardized screening for stress and depression, 62% had stress levels associated with increased cardiac risk, and 27% met criteria for clinical depression. CONCLUSIONS: Hypertension, dyslipidemia, and/or impaired fasting glucose were newly identified in approximately half the women screened. Waist size significantly correlated with clustering of risk factors, global Framingham risk score, CVD and diabetes, suggesting it may be an easily measured surrogate for women at increased risk of future cardiovascular clinical events who may benefit from further assessment and intervention.

Association of blood pressure indices and stroke mortality in isolated systolic hypertension.

BACKGROUND AND PURPOSE: Isolated systolic hypertension (ISH), systolic blood pressure (BP) > or =160 mm Hg and diastolic BP (DBP) <90 mm Hg, is associated with stroke; however, the correlation between specific BP indices and stroke mortality in ISH is not defined. METHODS: In a pooled analysis of 9 epidemiological studies, we examined whether pulse pressure (PP) was more predictive of stroke mortality than systolic BP (SBP), DBP, or mean BP (MAP) in persons with ISH. Subjects (n=682; 29% male; 77% white; mean age 63.6 years) with ISH, free of cardiovascular disease, and not on antihypertensive drug therapy at baseline were followed a mean of 13.0+/-7.3 years, and 54 stroke deaths occurred. The relative importance of each BP index was compared by the decrease in the -2 log likelihood (a measure of model agreement with data) because of the addition of 1 or a combination of BP indices to a Cox regression model. Hazards ratios (HRs) for fatal stroke for a 1-SD in BP index were determined. RESULTS: PP was the best predictor of stroke mortality based on the decrease in the -2 log likelihood (10.65; P=0.001; HR=1.52), followed by SBP (7.19; P=0.007; HR=1.40), DBP (2.76; P=0.10; HR=0.80), or MAP (0.39; P=0.39; HR=1.10). Any combination of BP indices did not exceed a decrease in the -2 log likelihood of 10.72. CONCLUSIONS: These data suggest that in persons with ISH, PP is a better predictor of fatal stroke than SBP, DBP, or MAP.

Prevalence of breast arterial calcifications in an ethnically diverse population of women.

PURPOSE: Breast arterial calcifications (BAC) identified on routine mammography have been associated with coronary heart disease (CHD) risk factors including diabetes and hypertension, angiographically defined CHD, and increased cardiovascular mortality. Accumulating evidence suggests that the mammogram may be an important tool to identify women at risk for CHD, however, the epidemiology of BAC has been poorly defined and previous studies limited to white populations. METHODS: The mammograms of 1905 consecutive women (51.2% Hispanic, 25.8% white, 15.3% black, 5.4% other, 2.2% Asian, ages 35-92 years) were evaluated for the presence of BAC and the number of calcified arteries. RESULTS: The overall prevalence of BAC was 29.4% and was significantly higher for Hispanics compared with whites (34.5% vs. 24.0%, p=0.0002) and lower for Asians compared with whites (7.1% vs. 24.0%, p < 0.02). Among BAC-positive women aged 65 years or less, blacks had more calcified arteries than whites (p < 0.01). The presence of BAC increased with age (p for trend < 0.0001). In age-adjusted models, older Hispanics were more likely to be BAC-positive than whites of similar age (p < 0.02). CONCLUSION: These results indicate that BAC varies significantly by age and race/ethnicity. These findings should be taken into consideration when designing future studies of BAC and CHD.

The gender gap in coronary heart disease mortality: is there a difference between blacks and whites?

BACKGROUND: The gender difference (gender gap) in mortality due to coronary heart disease (CHD) decreases with age. This relationship has not been well characterized in diverse populations. METHODS: To examine the gender gap in CHD mortality across age groups and to compare the age dependency of the gender gap between blacks and whites, we conducted a prospective cohort study combining data from 9 U.S. epidemiological studies (Atherosclerosis Risk in Communities Study [ARIC], Charleston Heart Study, Evans County Study, Framingham Heart Study [original and offspring cohorts], National Health Examination Follow-up Study [NHEFS], Rancho Bernardo Study, San Antonio Heart Study, and Tecumseh Community Health Study). Baseline examinations were performed between 1958 and 1990 (depending on the study), and mean follow-up was 13.7 years in general communities in several U.S. geographic areas. We included 39,614 subjects >30 years and free of cardiovascular disease (CVD) at baseline (18% blacks, 37% men). Completion of follow-up was >97% for all studies. As the main outcome measures, age-specific CHD mortality rates and male/female CHD mortality hazard ratios were calculated using Cox hazards regression. RESULTS: During 542,605 person-years of follow-up, 2,812 CHD deaths were observed (18% in blacks, 46% in men). At age 45, white men were at a 6-fold increased risk compared with white women (95% confidence interval [95% CI] 4.6-7.9), whereas black men had a 2-fold increased risk of fatal CHD compared with black women (1.4-3.6). At age 95, men and women were at equal risk in both whites (0.9-1.4) and blacks (0.7-1.6). The difference in the age dependency of the gender gap between blacks and whites was significant (p < 0.0001). CONCLUSIONS: The gender difference in CHD mortality was more pronounced in whites than in blacks at younger ages. This discrepancy was not explained by adjustment for CHD risk factors and suggests that other factors may be responsible for the ethnic variation in the gender gap.

The association between educational level and risk of cardiovascular disease fatality among women with cardiovascular disease.

BACKGROUND: The inverse relation of socioeconomic status with incident cardiovascular diseases (CVDs) has been well established. However, few data are available describing this relation among ethnically diverse women with prevalent CVD. Using education as a proxy for socioeconomic status, we examined its relation to CVD mortality among women with established CVD. SUBJECTS: Data from 2,157 women with CVD at baseline, who participated in nine long-term U.S. cohort studies, were pooled. METHODS: Cox regression models adjusted for history of diabetes mellitus, total cholesterol, systolic and diastolic blood pressure, body mass index, smoking, race/ethnicity, and age at baseline were used to estimate hazard ratios for CVD mortality between non-high school graduates and high school graduates. RESULTS: During a mean follow-up time of 11.5 years, 615 CVD deaths were observed. There was an age-dependent (p = .003) inverse association between education and CVD mortality among women with CVD. At age 60, the risk of dying due to CVD among non-high school graduates was more than twice greater than that of high school graduates (hazard ratio = 2.34; 95% CI 1.27-4.29). At age 65, the hazard ratio decreased to 1.31 (95% CI 1.00-1.71). By age 70, there was no difference in the hazard of dying between high school graduates and nongraduates (hazard ratio = 1.01; 95% CI .85-1.21). CONCLUSIONS: Our results show that among women with CVD, educational level was a significant, and age-dependent, predictor of fatal CVD independent of other traditional risk factors. These women are an important high-risk population to target secondary prevention and educational efforts.

Is diabetes mellitus a cardiovascular disease risk equivalent for fatal stroke in women? Data from the Women's Pooling Project.

BACKGROUND AND PURPOSE: Diabetes mellitus is an independent risk factor for stroke and is associated with a 1.8- to approximately 6-fold increased risk compared with nondiabetic subjects. Recent guidelines have classified diabetes as a coronary heart disease risk equivalent. Whether diabetes is a cardiovascular disease risk equivalent for stroke is not established. METHODS: Data were pooled from 9 prospective epidemiological studies in the United States. We followed up 27,269 women (8.5% diabetic, 2.9% with prior myocardial infarction, 2.3% with prior stroke) for an average of 8.3 years, during which 238 stroke deaths were observed. RESULTS: Both diabetic subjects without cardiovascular disease and nondiabetic subjects with history of prior stroke had a significantly increased risk of 10-year stroke mortality compared with nondiabetic subjects without prior cardiovascular disease (hazard ratio [HR], 6.77; 95% confidence interval [CI], 4.56 to 10.05; HR, 3.37; 95% CI, 2.38 to 4.77). History of prior myocardial infarction was not associated with long-term stroke mortality (HR, 0.66; 95% CI, 0.27 to 1.61). After adjustment for risk factors, diabetic subjects had similar risk compared with subjects with a history of prior stroke (HR, 1.29; P=0.43). CONCLUSIONS: Diabetic subjects without cardiovascular disease have a fatal stroke risk similar to that of nondiabetic subjects with a history of prior stroke and similar risk factor profile. This suggests that diabetes mellitus may be classified as a stroke risk equivalent and may warrant more aggressive treatment strategies in the future prevention of stroke.

Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.

Plasma lipoprotein [a] (Lp[a]) concentrations are inversely associated with, and largely determined by, apolipoprotein [a] (apo[a]) gene size, a highly polymorphic trait. We studied if, within an individual, the smaller apo[a] isoform always dominated, whether there was interaction between the two alleles, and whether these features differed between Caucasians and African Americans. We determined apo[a] gene sizes, apo[a] protein sizes and relative amounts, and plasma Lp[a] levels in 430 individuals (263 Caucasians and 167 African Americans). Of the 397 heterozygotes with at least one detectable apo[a] isoform (238 Caucasians and 159 African Americans), the larger allele dominated in 28% of Caucasians and 23% of African Americans, while the smaller allele dominated in 56% of Caucasians and 45% of African Americans. In Caucasians, dominance of the smaller allele increased with Lp[a] levels, from 44% at Lp[a] < or = 30 nM to 81% at Lp[a] >100 nM (P < 0.0001). Dominance by the smaller allele increased with increasing size of the larger allele in both groups but with the smaller allele only in African Americans. There was no interaction between apo[a] alleles within genotypes; one apo[a] isoform level was not associated with the other isoform level, and isoform levels were not affected by the difference in size. More of the dominance pattern was explained by Lp[a] level and apo[a] genotype in African Americans than in Caucasians (29% vs. 13%). Thus, genotype influences isoform-specific Lp[a] levels and dominance patterns differently in African Americans and in Caucasians.

Relation of Apo(a) size to carotid atherosclerosis in an elderly multiethnic population.

Lipoprotein(a) [Lp(a)] is a novel risk factor for atherosclerosis, whose role in multiracial populations has been debated. We recently demonstrated a significant association of elevated levels of Lp(a) carried in particles containing small apolipoprotein(a) [apo(a)] isoforms with coronary artery disease in African American and white men. To extend these findings, we investigated the associations between Lp(a) levels, apo(a) size, and maximum internal carotid artery plaque thickness (MPT) in a randomly selected elderly multiethnic population (173 men and 253 women, consisting of 135 African Americans, 146 Hispanics, and 145 whites; mean age 70.5+/-11.4 years). Lp(a) levels were not associated with MPT. Among white men, MPT was associated with a small apo(a) isoform size (P=0.03) as well as with the amount of Lp(a) carrying the small apo(a) size (P=0.04), and the latter showed a borderline association in African American men (P=0.07). Among white women, but not in Hispanic or African American women, MPT was associated with the amount of Lp(a) carrying a small apo(a) isoform size (P<0.01). For all patients, the amount of Lp(a) carrying the small apo(a) size was associated with carotid atherosclerosis when there was control for age, sex, ethnicity, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, diabetes mellitus, hypertension, waist-to-hip ratio, and current smoking status (P=0.03). This association was significant for all men (P=0.03) and for white women (P=0.007). The results suggest that molecular properties of apo(a) are important in determining the atherogenicity of Lp(a).