Serum non-esterified fatty acid levels and hip fracture risk: The Cardiovascular Health Study.

Among elderly participants from the Cardiovascular Health Study, we found that non-esterified trans fatty acid levels had a significant prospective association with hip fracture risk. Other non-esterified fatty acid classes were not associated with hip fracture risk. INTRODUCTION: Serum non-esterified fatty acids (NEFAs) are bioactive metabolic intermediates that can be taken up by bone tissue. Their associations with hip fracture risk have not been previously examined. METHODS: Thirty-five individual NEFAs in five classes (saturated [SFA], mono-un-saturated [MUFA], poly-unsaturated n-6 and n-3 [PUFA], and trans-FA) were measured in Cardiovascular Health Study participants (n = 2139, mean age 77.8 years) without known diabetes. The multivariable associations of NEFA levels with hip fracture risk were evaluated in Cox hazards models. RESULTS: We documented 303 incident hip fractures during 11.1 years of follow-up. Among the five NEFA classes, total trans FA levels were positively associated with higher hip fracture risk (HR 1.17 [95% CI, 1.04, 1.31; p = 0.01] per one standard deviation higher level). The SFA lignoceric acid (24:0) was positively associated with higher risk (HR 1.09 [1.04, 1.1]; p < 0.001), while behenic (22:0) and docosatetraenoic (22:4 n6) acids were associated with lower risk (HR 0.76 [0.61, 0.94]; p = 0.01; 0.84 [0.70, 1.00]; p = 0.05, respectively). CONCLUSION: Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.

Assessing risk factors of non-fatal outcomes amid a competing risk of mortality: the example of hip fracture.

The Fine-Gray method is often used instead of Cox regression to account for competing risks of death in time-to-event analyses for non-fatal outcomes. A series of examples using well-known risk factors of hip fracture in an older cohort with substantial competing mortality demonstrates that the Fine-Gray approach can yield estimates that implausibly contradict long-established associations, while Cox regression preserves them. Cox regression is generally preferred for risk factor-outcome associations even in the presence of competing risk of death. INTRODUCTION: Factors like age, sex, and race are associated not only with risk of hip fracture but also with mortality. Substantial misunderstanding remains regarding the appropriate statistical approach to account for the competing risk of mortality. METHODS: In the Cardiovascular Health Study, an ongoing cohort study of 5888 older adults, we followed participants for incident hip fracture from their 1992-1993 visit through June 2014. We contrasted the conventional cause-specific Cox analysis, which censors individuals at the time of death, with the Fine-Gray (FG) approach, which extends participant follow-up even after death, to estimate the association of well-established demographic and clinical factors with incident hip fracture. RESULTS: For age, current smoking and sex, Cox and FG methods yielded directionally concordant but quantitatively different strengths of association. For example, the Cox hazard ratio (HR) for a 5-year increment in age was 1.74 (95% CI, 1.61-1.87), while the corresponding FG HR was 1.16 (1.09-1.24). In contrast, the FG approach estimated a stronger association of hip fracture with sex. The two approaches yielded nearly identical results for race. For diabetes and kidney function, the estimates were discordant in direction, and the FG HRs suggested effects that were in the opposite direction of well-understood and widely accepted associations. CONCLUSIONS: Cause-specific Cox models provide appropriate estimates of hazard for non-fatal outcomes like hip fracture even in the presence of competing risk of mortality. The Cox approach estimates hazard in the population of individuals who have not yet had an incident hip fracture and remain alive, which is typically the group of clinical interest. The Fine-Gray method estimates hazard in a hypothetical population that can yield misleading inferences about risk factors in populations of clinical interest.

The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD. INTRODUCTION: Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain. METHODS: We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7 ± 5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing. RESULTS: There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk. CONCLUSION: Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.

Soluble CD14 and fracture risk.

UNLABELLED: Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture. INTRODUCTION: Soluble CD14, a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts. The purpose of this study was to examine the relationship between sCD14 levels and osteoporotic fractures. METHODS: In the Cardiovascular Health Study, 5462 men and women had sCD14 levels measured at baseline. Incident hip fractures (median follow-up time 12.5 years) and incident composite fractures (defined as the first hip, pelvis, humerus, or distal radius fracture, median follow-up 8.6 years) were identified from hospital discharge summaries and/or Medicare claims data. Cox proportional hazards models were used to model the association between sCD14 levels and time to incident hip or composite fracture, overall and as a function of race and gender. RESULTS: In unadjusted models, there was a positive association between sCD14 levels (per 1 standard deviation increase, i.e., 361.6 ng/mL) and incident hip (HR, 1.26; 95 % CI, 1.17, 1.36) and composite (HR, 1.20; 95 % CI, 1.12, 1.28) fractures. When models were fully adjusted for demographics, lifestyle factors, and medication use, these associations were no longer significant. However, in whites, the association of sCD14 levels with hip fractures remained significant in fully adjusted models (HR, 1.11; 95 % CI, 1.01-1.23). Associations of sCD14 levels with hip and composite fracture did not differ between men and women. CONCLUSIONS: In this large cohort of community-dwelling older adults, higher sCD14 levels were associated with an increased risk of incident hip fractures in whites.

Fibrosis markers, hip fracture risk, and bone density in older adults.

UNLABELLED: We examined whether blood levels of two markers of fibrosis (transforming growth factor beta one (TGF-ß1) and procollagen type III N-terminal propeptide (PIIINP)) are related to hip fracture risk and to bone mineral density (BMD). TGF-ß1 levels were associated with lower hip fracture risk in women and with lower BMD in men. PIIINP levels were not associated with either outcome. INTRODUCTION: TGF-ß1 serves several roles in bone formation and resorption. A consequence of TGF-ß1 activation is the production of PIIINP, a marker of collagen III deposition. Here, we explore whether these two biomarkers are related to incident hip fracture and bone mineral density (BMD) and whether their associations are modified by systemic inflammation, as measured by C-reactive protein (CRP) levels. METHODS: Participants were from the Cardiovascular Health Study (mean age 78 years; mean follow-up 8.3 years). We included 1681 persons with measured levels of TGF-ß1 (149 hip fractures) and 3226 persons with measured levels of PIIINP (310 hip fractures). RESULTS: Among women, higher TGF-ß1 levels were associated with lower hip fracture risk (HR, per doubling, 0.78 [95 % CI 0.61, 0.91]). Among men, TGF-ß1 levels were associated with hip fracture risk in a non-linear manner, but among those with elevated CRP levels, doubling was associated with increased risk of fracture (HR 2.22 [1.20, 4.08]) (p = 0.02, interaction between low and high CRP and TGF-ß1 on fracture risk). TGF-ß1 levels had no significant association with total hip or total body BMD in women but were significantly associated with lower BMD in men. There were no associations of PIIINP levels with hip fracture risk or BMD in men or women. CONCLUSIONS: TGF-ß1 levels appear to be associated with bone-related phenotypes in a sex-specific manner. The reasons for these differences between men and women regarding TGF-ß1 levels and hip fracture risk and bone density require further investigation.

Systemic markers of microvascular disease and bone mineral density in older adults : The cardiovascular health study.

Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders. INTRODUCTION: Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together. METHODS: BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors. RESULTS: AWMD was associated with lower hip, spine, and total body BMD in women (ß -3.08 to -4.53; p < 0.01 for all) and lower hip and total body BMD in men (ß -2.90 to -4.24; p = 0.01-0.03). Albuminuria was associated with lower hip (ß -3.37; p = .05) and total body (ß -3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women. CONCLUSION: AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies.

Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study.

UNLABELLED: The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men. INTRODUCTION: The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30 mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78 years. METHODS: From the Cardiovascular Health Study (41 % male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5 years. BMD was performed in a subset of 1,208 participants. RESULTS: There were 313 hip fractures during follow-up (7.7 % of men; 11.7 % of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95 % CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009 g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women. CONCLUSIONS: In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

The c-fos proto-oncogene in murine 3LL carcinoma clones controls the expression of MHC genes.

The c-fos proto-oncogene and H-2K class I major histocompatibility antigens are differentially expressed in low-metastatic Lewis lung carcinoma clones, but not in high-metastatic clones. Interferons induce mRNA expression of fos and H-2 in non-expressor cells and elevate mRNA steady state levels of expressor cells. Transfection of non-expressor cells by v-fos or c-fos genes induces the transcription of H-2K mRNA and elevates the levels of H-2 proteins, but not of other gene products. These results, correlated with observations in other cell systems, suggest that the c-fos proto-oncogene controls the expression of MHC genes coding for class 1 antigens.

Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy.

Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study. From an inception cohort of patients with juvenile-onset IDDM that now has 15-21 yr diabetes duration, the patients with PDR (cases, n = 74) were selected for study along with a random sample of the patients in the cohort without PDR (control subjects, n = 88). The risk of PDR was associated with poor glycemic control during the first 12 yr of diabetes. Relative to patients in the first quartile of the index of hyperglycemia, those in higher quartiles and nonattenders had a four- to fivefold risk of developing PDR. A striking relationship with cardiovascular autonomic neuropathy (CAN) was found. Relative to patients without CAN, patients with significant and mild CAN had odds ratios of 77.5 and 34.6, respectively. Patients with albumin excretion rates greater than 30 micrograms/min had moderately increased risk of PDR (ranging from 4-fold for microalbuminuria to 7-fold for proteinuria). In contrast, patients with impaired renal function had an extremely high risk of PDR. All 20 of these patients were cases, therefore the odds ratio was infinite. All three factors (poor glycemic control, CAN, and various stages of nephropathy) were associated with PDR in multiple logistic regression analysis. However, in models including glycemic control, the association between microalbuminuria or proteinuria and PDR was weakened. In conclusion, our findings are consistent with a hypothesis that the level of glycemia is a primary determinant of early-onset PDR.(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.

Expression of major histocompatibility class I genes in differentiating leukemic cells is temporally related to activation of c-fos proto-oncogene.

The relationship between the expression of the c-fos proto-oncogene and the expression of the class I major histocompatibility (MHC) antigens during the early stages of induced differentiation in three different leukemic cell lines was examined. In the U937 histiocytic lymphoma line TPA induced an increase in mRNA and cell surface MHC expression which followed induction of c-fos. In contrast, in the murine erythro-leukemia cell line, DMSO induced declining constitutive c-fos levels that were accompanied by declining mRNA and cell surface MHC expression. In the pluripotent HL60 promyelocytic line induction of macrophage differentiation with TPA led to c-fos induction and rising MHC levels, whereas induction of granulocyte differentiation with DMSO did not induce c-fos expression and was followed by declining MHC levels. Taken together, the results suggest that the c-fos proto-oncogene might be involved in the control of class I MHC antigen expression during differentiation.

Benign and malignant tumors in patients with acromegaly.

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.

Increased expression of Fc gamma receptor in cancer patients and tumor bearing mice.

In this study we report on some lines of ongoing research performed in our laboratory, in relation to the increased expression of FcR on tumor cells, as well as on cells present in the tumor-bearing host, and its possible role in tumor progression. In a previous study we have shown that a Polyoma virus (PyV)-induced anaplastic carcinoma (SEYF-a tumor) contained an FcR-expressing subpopulation of tumorigenic cells. We tested the effect of in vivo passaging of FcR-expressing and of non-FcR-expressing sub-populations of SEYF-a tumor cells on the expression of FcR, as revealed by the ability of these cells to bind the 2.4G2 monoclonal antibody, which is directed against mouse Fc gamma 2b/gamma 1R. It was found that upon in vivo passaging these two sub-populations became practically identical in their ability to bind anti-Fc gamma R antibody. On the other hand, in vitro passaging of FcR-expressing SEYF-a cells resulted in a gradual decrease in the expression of Fc gamma R. These results, indicating that the expression of Fc gamma R on tumor cells, per se, is dependent on a factor present in the in vivo environment were confirmed using 3T3 cells transformed in vitro by PyV (C) and forming tumors at first injection to mice (CTC). C cultures of various clones did not express Fc gamma R, while CTC cultures (cultures from tumors) became positive. We also detected an increase in the level of a soluble form of Fc gamma 2b/gamma 1R in the circulation of mice bearing PyV induced tumors. This increase paralleled the appearance of palpable tumors. A similar pattern of increase was observed in mice inoculated with the c-H-ras transformed tumorigenic clone 8/F/5, but not in mice inoculated with non-tumorigenic 3T3 cells. Data published by us show that metastatic breast cancer patients had significantly elevated Fc gamma R levels on their peripheral blood mononuclear cells (PBMC). Experiments presented here indicate a direct correlation between increased Fc gamma R levels on PBMC and tumor mass in colon, ovary and lung metastatic carcinoma patients. The possibility that malignantly transformed cells have the potential to cause proliferation of Fc gamma R expressing T cells was tested. It was found that extract derived from r-H-ras transformed 3T3 cells triggers the proliferation of a T cell hybridoma expressing Fc gamma R.

Coronary artery disease in diabetic patients with lower-extremity arterial disease: disease characteristics and survival. A report from the Coronary Artery Surgery Study (CASS) registry.

OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.

Lactic acidosis rates in type 2 diabetes.

OBJECTIVE: To provide a context for the interpretation of lactic acidosis risk among patients using metformin, we measured rates of lactic acidosis in patients with type 2 diabetes before metformin was approved for use in the U.S. RESEARCH DESIGN AND METHODS: Using electronic databases of hospital discharge diagnoses and laboratory results maintained by a large, nonprofit health maintenance organization (HMO). we identified possible lactic acidosis events in three geographically and racially diverse populations with type 2 diabetes. We then reviewed hard-copy clinical records to confirm and describe each event and determine its likely cause(s). RESULTS: From >41.000 person-years of experience, we found four confirmed, three possible, and three borderline cases of lactic acidosis. In each case, we identified at least one severe medical condition that could have caused the acidosis. The annual confirmed event rate is similar to published rates of metformin-associated lactic acidosis. CONCLUSIONS: Lactic acidosis occurs regularly, although infrequently, among persons with type 2 diabetes, at rates similar to its occurrence among metformin users. The medical conditions with which both metformin-associated and naturally occurring lactic acidosis co-occur are also its potential causes. The observed association between metformin and lactic acidosis may be coincidental rather than causal. This possibility merits further study

Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort. RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes. RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997. CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.

Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

OBJECTIVE: Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. RESEARCH DESIGN AND METHODS: The Antihypertensive and Lipid-Lowering high-risk hypertensive participants, ages > or = 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002. RESULTS: There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, treatments for the two study outcomes. CONCLUSIONS: The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

Coronary artery disease and coronary artery bypass grafting in diabetic patients aged > or = 65 years (report from the Coronary Artery Surgery Study [CASS] Registry).

A cohort of 317 diabetic patients, aged > or = 65 years, with angiographically proven coronary artery disease, was analyzed and followed for a mean of 12.8 years. Compared with 1,843 age-matched nondiabetic patients, diabetic patients were more likely to (1) have a higher number of coronary occlusions, (2) not be current smokers, (3) have higher systolic but lower diastolic blood pressures, (4) have evidence of peripheral vascular disease, and (5) be women. They did not differ significantly with respect to total cholesterol, family history of coronary artery disease, history of hypertension, or left ventricular hypertrophy. In the total elderly cohort, diabetes was found to be an independent predictor of mortality, conferring a 57.0% increased risk of death. Survival analysis showed that diabetic subjects consistently had higher mortality than nondiabetics. However, the relative survival benefit of coronary artery bypass graft surgery versus medical therapy was comparable in diabetic and nondiabetic patients. Surgical therapy conferred a reduction in mortality of 44%.

Frequency and prognostic significance of high-degree atrioventricular block in patients with a first non-Q-wave acute myocardial infarction. The SPRINT Study Group. Second Prevention Reinfarction Israeli Nifedipine Trial.

Patients with a first non-Q-wave acute myocardial infarction with high-degree atrioventricular block were compared with patients without atrioventricular block. In-hospital complications and mortality were significantly higher among patients with atrioventricular block; atrioventricular block emerged as an important prognostic predictor of early mortality in these patients.