Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls.

Objective We tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythematosus (SLE) compared with healthy controls (HCs). Methods Among 611 women in two age- and race-matched SLE case-control studies, OPG was assayed in stored blood samples (HEARTS: plasma, n cases/controls = 122/124, and SOLVABLE: serum, n cases/controls = 185/180) and CAC was measured by electron beam computed tomography. Results In both studies, SLE patients had higher OPG and CAC levels than HCs. Higher OPG was associated with high CAC (>100 vs.100) among SLE, and with any CAC (>0 vs. 0) among HCs. Multivariable-adjusted OR (95% CI) for OPG tertile 3 vs. 1 was 3.58 (1.19, 10.76), p trend = 0.01 for SLE, and 2.28 (1.06, 4.89), p trend = 0.04 for HCs. Associations were attenuated when age-adjusted, but remained significant for HC women aged ≥ 40 and SLE women aged ≥ 50. ROC analyses identified 4.60 pmol/l as the optimal OPG cutpoint for predicting high CAC (>100) among SLE patients with sensitivity = 0.74 and specificity = 0.61, overall, but 0.92 and 0.52, respectively, for SLE patients aged ≥ 50. Conclusion Our cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.

Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

Association analysis of 33 lipoprotein candidate genes in multi-generational families of African ancestry.

African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21-113, 3,426 relative pairs). All lipoproteins were significantly heritable (P<0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P<0.01) in women than in men (women, 0.62+/-0.18, P<0.01; men, 0.13+/-0.17, P>0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P<0.05) in men than in women (men, 0.79+/-0.21, P<0.01; women, 0.39+/-0.12, P<0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.

Breast cancer study.

In the report "Spacelab-2 plasma depletion experiments for ionospheric and radio astronomical studies" by M. Mendillo et al. (27 Nov., p. 1260), figure 5A (p. 1263) was misplaced with respect to figure 5B so that the scale of figure 5A was incorrectly represented. A correct figure 5 is printed below.

Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression. OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

Coronary heart disease mortality and adjuvant tamoxifen therapy.

BACKGROUND AND PURPOSE: Data from randomized clinical trials in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease. In view of these findings, we examined mortality from coronary heart disease among patients with early stage breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy. METHODS: Deaths occurring among women who were randomly assigned to 5 years of either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to determine the cause. Three categories of heart disease-related death were defined: 1) death from a definite fatal myocardial infarction, 2) death from definite fatal coronary heart disease/possible myocardial infarction, and 3) death from possible fatal coronary heart disease. Comparisons of the findings by treatment group were made on the basis of average annual hazard (i.e., death) rates and the corresponding relative hazard of death. RESULTS: The average annual death rate from coronary heart disease was lower for patients who received tamoxifen than for patients who received placebo, but the difference was not statistically significant. There were eight definite heart-related deaths (i.e., definite fatal myocardial infarction or definite fatal coronary heart disease/possible myocardial infarction) among the patients who received tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were 12 definite heart-related deaths among the patients who received placebo, yielding an average annual rate of 0.94 per 1000. The corresponding relative hazard of death from definite fatal heart disease (tamoxifen versus placebo) was 0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group and 10 deaths in the placebo group were classified as possible cases of fatal coronary heart disease. When these cases and the definite cases were considered together, the average annual death rate for the patients who received tamoxifen was 1.48 per 1000, and the rate for the patients who received placebo was 1.73 per 1000. The corresponding relative hazard of death was 0.85 (95% confidence interval = 0.46-1.58). CONCLUSIONS: The findings from the B-14 trial are consistent with the findings from the Scottish and the Swedish trials, suggesting that tamoxifen treatment reduces coronary heart disease among patients with breast cancer. Continued follow-up of the patients in these trials and in ongoing prevention trials is needed to accumulate enough data so that reliable conclusions can be drawn about the benefits of tamoxifen in preventing heart disease.

Increased blood glucose and insulin, body size, and incident colorectal cancer.

BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer. METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided. RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02). CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.

Bone mass and breast cancer risk in older women: differences by stage at diagnosis.

BACKGROUND: Older women with low bone mineral density (BMD) have a decreased incidence of breast cancer. It is not known whether this association is confined to early-stage, slow-growing tumors. METHODS: We prospectively studied 8905 women who were 65 years of age or older during the period from 1986 through 1988 and had no history of breast cancer. At study entry, we used single-photon absorptiometry to measure each woman's BMD at three skeletal sites: the wrist, forearm, and heel. The women were followed for a mean of 6.5 years for the occurrence of breast cancer. All statistical tests were two-sided. RESULTS: During 57 516 person-years of follow-up, 315 women developed primary invasive or in situ breast cancer. Multivariate analyses that adjusted for age, obesity, and other covariates revealed that the risk of breast cancer for women in the highest quartile of BMD for all three skeletal sites was 2.7 (95% confidence interval [CI] = 1.4 to 5.3) times greater than that for women in the lowest quartile at all three skeletal sites. The magnitude of increased risk associated with high BMD differed by the stage of disease at diagnosis and was greater for more advanced tumors (relative risk [RR] for TNM [i.e., tumor-lymph node-metastasis] stage II or higher tumors = 5.6; 95% CI = 1.2 to 27.4) than for early-stage disease (RR for in situ/TNM stage I tumors = 2.2; 95% CI = 1.0 to 4.8). CONCLUSIONS: Elderly women with high BMD have an increased risk of breast cancer, especially advanced cancer, compared with women with low BMD. These findings suggest an association between osteoporosis and invasive breast cancer, two of the most prevalent conditions affecting an older woman's health.

The Associations of C-Reactive Protein with Serum Levels of Polyunsaturated Fatty Acids and Trans Fatty Acids Among Middle-Aged Men from Three Populations.

BACKGROUND: C-reactive protein (CRP) and many fatty acids (FAs) have been linked to cardiovascular disease. Associations of serum CRP with FAs in different populations have not been established. METHODS: Participants were 926 men aged 40-49 (2002-2006) from a population-based sample; 310 Whites from Pennsylvania, U.S., 313 Japanese from Shiga, Japan, and 303 Japanese Americans from Hawaii, U.S. Serum CRP (mg/L) was measured using immunosorbent assay while serum FAs (%) were measured using capillary-gas-liquid chromatography. RESULTS: Whites had CRP (mg/L) levels higher than Japanese with Japanese Americans in-between (age-adjusted geometric mean "GM" 0.96, 0.38, 0.66, respectively). Whites had also higher levels of total n-6 FAs (%) and trans fatty acids (TFAs) but lower levels of marine-derived n-3 FAs compared to Japanese (41.78 vs. 35.05, 1.04 vs. 0.58, and 3.85 vs. 9.29, respectively). Japanese Americans had FAs levels in-between the other two populations. Whites had significant inverse trends between CRP and tertiles of total n-6 FAs (GM 1.20, 0.91 and 0.80; p=0.002) and marine-derived n-3 FAs (GM 1.22, 1.00 and 0.72; p<0.001) but a significant positive trend with TFAs (GM 0.80, 0.95 and 1.15; p=0.007). Japanese had a significant inverse trend between CRP and only total n-6 FAs (GM 0.50, 0.35 and 0.31; p<0.001). Japanese Americans had CRP associations with n-3 FAs, n-6 FAs, and TFAs similar to but weaker than Whites. CONCLUSIONS: With the exception of consistent inverse association of CRP with total n-6 FAs, there are considerable variations across the three populations in the associations of CRP with different FAs.

Women's Healthy Lifestyle Project: A randomized clinical trial: results at 54 months.

BACKGROUND: The Women's Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause. METHODS AND RESULTS: There were 275 premenopausal women randomized into the assessment only group and 260 women into the intervention group. The mean age of participants at baseline was 47 years, and 92% of the women were white. The mean LDL cholesterol was 115 mg/dL at baseline, and mean body mass index was 25 kg/m(2). The follow-up through 54 months was excellent. By 54 months, 35% of the women had become postmenopausal. At the 54-month examination, there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment-only group (P:=0.009). Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment-only group (P:=0.000). Triglycerides and glucose also increased significantly more in the assessment-only group than in the intervention group. Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment-only group (P:=0.000). CONCLUSIONS: The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol. The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause. The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers.

Coronary artery calcification in older adults to age 99: prevalence and risk factors.

BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied. METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile. CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.

BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (

Sudden cardiac death, genes, and arrhythmogenesis : consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I.

Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.

Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute workshop, Part II.

This is Part II of a 2-part article dealing with malignant ventricular arrhythmias, which are the leading mechanism of death in common cardiac diseases. Genetic population studies directed at discovering common proximal sources of inherited molecular risk most directly linked to arrhythmia initiation and propagation would appear to have considerable potential in helping reduce cardiovascular mortality.

Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women.

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

In light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.

The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study. Mortality results.

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Children's Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U.S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

The Pittsburgh insulin-dependent diabetes mellitus (IDDM) registry. The incidence of insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania (1965-1976).

An insulin-dependent Diabetes Mellitus Registry has been developed in Allegheny County, Pennsylvania, through hospital record review and surveillance of pediatric practices. The yearly incidence ranged from 10/100,000 for nonwhite males to 16/100,000 for white males. There were no temporal trends in incidence for 1965-1976 nor major sex differences. Nonwhites had a slightly lower incidence, primarily in the younger age groups.

Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II.

The prevalence of and interrelationships among all four major complications of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a large epidemiologic study of IDDM subjects diagnosed in childhood. This article focuses on the baseline prevalence of complications in the 657 subjects diagnosed between 1950 and 1980 and currently aged 8-48 yr, with a mean duration of 20 yr. In addition to background retinopathy being virtually universal after 20 yr of diabetes, proliferative retinopathy affects 70% of IDDM subjects after 30 yr duration. As with overt nephropathy, prevalence of proliferative retinopathy is marginally higher in females than in males at short durations; the previously reported male excess is limited to the subjects with IDDM of longer duration (greater than or equal to 25 yr). Somewhat different patterns of microalbuminuria are also seen by sex. Males show a threefold increase in prevalence from 10 to 25 yr duration, whereas females show a more constant prevalence across these durations. A further rise in microalbuminuria is seen in males but not females at greater than or equal to 30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at greater than or equal to 30 yr duration of 84% (males) and 59% (females). Distal symmetrical polyneuropathy shows a constant rise with duration and is only marginally higher in men. Prevalence of cardiovascular (coronary and cerebral) disease shows no sex difference, whereas peripheral vascular disease is particularly common in women after 30 yr duration (greater than 30%) compared with men (11%) when determined by ankle/arm blood pressure ratio less than 0.8 at rest or after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.