Biomedical subjects

Samer S Najjar

Publications and source records attributed to Samer S Najjar.

16 recordsLinked to original sources

PubMed2006

Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction.

OBJECTIVES: The purpose of this study was to identify cardiovascular features of patients with heart failure with preserved ejection fraction (HFpEF) that differ from those in individuals with hypertensive left ventricular hypertrophy (HLVH) of similar age, gender, and racial background but without failure. BACKGROUND: Heart failure with preserved ejection fraction often develops in HLVH patients and involves multiple abnormalities. Clarification of changes most specific to HFpEF may help elucidate underlying pathophysiology. METHODS: A cross-sectional study comparing HFpEF patients (n = 37), HLVH subjects without HF (n = 40), and normotensive control subjects without LVH (n = 56). All subjects had an EF of >50%, sinus rhythm, and insignificant valvular or active ischemic disease, and groups were matched for age, gender, and ethnicity. Comprehensive echo-Doppler and pressure analysis was performed. RESULTS: The HFpEF patients were predominantly African-American women with hypertension, LVH, and obesity. They had vascular and systolic-ventricular stiffening and abnormal diastolic function compared with the control subjects. However, most of these parameters either individually or combined were similarly abnormal in the HLVH group and poorly distinguished between these groups. The HFpEF group had quantitatively greater concentric LVH and estimated mean pulmonary artery wedge pressure (20 mm Hg vs. 16 mm Hg) and shorter isovolumic relaxation time than the HLVH group. They also had left atrial dilation/dysfunction unlike in HLVH and greater total epicardial volume. The product of LV mass index and maximal left atrial (LA) volume best identified HFpEF patients (84% sensitivity, 82% specificity). CONCLUSIONS: In an urban, principally African American, cohort, HFpEF patients share many abnormalities of systolic, diastolic, and vascular function with nonfailing HLVH subjects but display accentuated LVH and LA dilation/failure. These latter factors may help clarify pathophysiology and define an important HFpEF population for clinical trials.

Age Distribution↗

PubMed2006

Heritability of cardiovascular and personality traits in 6,148 Sardinians.

In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits.

Adolescent↗

PubMed2006

Relation of angiotensin-converting enzyme inhibitor treatment to insulin-like growth factor-1 serum levels in subjects >65 years of age (the InCHIANTI study).

Observational studies have shown that the use of angiotensin-converting enzyme (ACE) inhibitors is associated with the maintenance of greater muscle strength and physical performance in older subjects. However, the mechanism that underlies these beneficial effects remains poorly understood. Because ACE inhibitors block the production of angiotensin II, which is a potent inhibitor of insulin-like growth factor-1 (IGF-1) production, it was hypothesized that treatment with ACE inhibitors is associated with higher levels of IGF-1. This hypothesis was tested in 745 subjects (417 women, 328 men) enrolled in the Invecchiare in Chianti study. Of these, 160 were receiving ACE inhibitors. The association between ACE inhibitor use and serum IGF-1 was tested by linear regression models. After adjusting for multiple potential confounders, serum levels of total IGF-1 were significantly higher in participants receiving ACE inhibitors (mean +/- SD 129.0 +/- 56.1 ng/ml) compared with the rest of the study population (mean +/- SD 116.5 +/- 54.8 ng/ml) (p <0.001). Participants with short (<3 years) and long (3 to 9 years) treatment durations had higher serum IGF-1 levels than participants who were not receiving ACE inhibitor treatment, but the difference was statistically significant only for the short-duration group (p <0.05). In conclusion, in older subjects, treatment with ACE inhibitors for <3 years is associated with significantly higher levels of IGF-1. This may be 1 of the mechanisms by which ACE inhibitors might slow the decreases in muscle strength and physical function that are often observed in older subjects.

Aged↗

PubMed2006

Echocardiographic findings in classical and hypermobile Ehlers-Danlos syndromes.

Structural cardiovascular alterations in the classical and hypermobile forms of Ehlers-Danlos syndrome(EDS) warrant investigation. We have examined a cohort of 38 patients with hypermobile and classical EDSs using two-dimensional echocardiography. The cohort includes 7 males and 31 females, with an age range from 12-60 years. Altered echocardiographic parameters were seen in the initial cross-sectional data analysis in 24/38 patients. Five of the 38 participants had mildly dilated aortic root (AR) or sinuses of Valsalva (SV), and an additional 7 patients had an abnormal pouching of the SV, although the absolute dimensions did not exceed the normal range. Ten patients had mild mitral, tricuspid, or aortic regurgitation, and only one patient had mitral valve prolapse (MVP). Three patients had low normal systolic function; three had evidence of mildly elevated pulmonary pressures, and two patients had mild concentric left ventricular hypertrophy (LVH). Five patients had evidence of impaired left ventricular relaxation (LVR) based on mitral valve E to A velocity ratio. Interestingly, 26/38 subjects demonstrated a prominent right coronary artery (RCA) easily visualized by trans-thoracic echocardiography, and 10/38 had an elongated cardiac silhouette on the 4-chamber apical views. The "pouching" shape of the SV was more common in hypermobile type than in the classical type of EDS. The study is ongoing and will accrue longitudinal data on 100 subjects with classical and hypermobile EDSs at 2-year intervals.

Adolescent↗

PubMed2006

Rapid titration of carvedilol in patients with congestive heart failure: a randomized trial of automated telemedicine versus frequent outpatient clinic visits.

BACKGROUND: Because of potential side effects and logistical difficulty of titrating medications, outpatients with congestive heart failure rarely receive appropriate doses of carvedilol or other beta-blockers. To address these obstacles, we studied if an automated telemedicine system named TeleWatch (TW) could facilitate carvedilol titration in outpatients with left ventricular systolic dysfunction. METHODS: Forty-nine patients with New York Heart Association class II and III left ventricular systolic dysfunction, who were tolerating appropriate afterload-reducing therapy and not receiving beta-blockers, were enrolled into a 3-month study. Patients were randomized to have clinic-only (CO) (n = 24) carvedilol titration or titrations which combined clinic visits with TW monitoring (n = 25). All patients were seen in clinic biweekly, and those in the TW group were remotely monitored daily. Using a predefined algorithm, patients in the CO and TW groups were eligible for carvedilol titration on a biweekly or weekly basis, respectively, by physicians blinded to group assignment. RESULTS: There was no statistical difference in the mean final daily dose of carvedilol between the CO and TW groups (39.4 vs 36.2 mg/d, P = .52). Because remote telemedicine titrations were as successful as titrations in the clinic, the time to reach the final dose of carvedilol was significantly shorter in the TW group (33.6 vs 63.7 days, P < .0001). There were 5 serious adverse events in the study, 4 of which were in the TW group (P = .29); however, TW prospectively detected 2 adverse events. CONCLUSIONS: Remote monitoring with an automated telemedicine system can successfully facilitate titration of carvedilol in outpatients with New York Heart Association class II and III congestive heart failure.

Adrenergic beta-Antagonists↗

PubMed2006

Suppressed anger is associated with increased carotid arterial stiffness in older adults.

BACKGROUND: Anger and hostility have been implicated in the pathogenesis of heart disease, but the extent to which the large conduit arteries play an intermediate role in this relationship remains to be clarified. The present study investigated associations of anger frequency and expression style with carotid artery intima-media thickness (IMT) and stiffness in healthy adults older than 50 years. METHODS: Two hundred participants (95 men) in the Baltimore Longitudinal Study of Aging completed the Spielberger Anger Expression Inventory, which assesses anger frequency (trait anger), anger expression (anger-out), and anger suppression (anger-in). The carotid artery IMT was assessed by ultrasonography. Carotid stiffness was determined from the log of systolic over diastolic blood pressure (BP) as a function of carotid distensibility. RESULTS: In univariate correlational analysis, a significant positive association of anger-in with stiffness was observed (P < .01), together with a less significant association of anger-in with carotid artery IMT (P < .05). Neither anger-out nor trait anger was significantly associated with carotid artery IMT or stiffness. Moreover, none of the anger measures was significantly associated with resting BP in this normotensive sample. As expected, carotid artery IMT, stiffness, and systolic BP were all positively associated. In multivariate analysis, anger-in remained a determinant of stiffness independent of BP, and a marginally significant determinant of carotid artery IMT. CONCLUSIONS: This is the first known finding that high anger-in is a significant independent determinant of carotid artery stiffness. These results suggest that high anger-in can potentiate the effects of age on stiffening of the central arteries.

Aged↗

PubMed2005

Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements.

Circulating testosterone levels (T) decrease with age in men. Low T has been associated with coronary disease and with risk factors for atherosclerosis. This study examines the relationship in men between androgenic hormones and arterial stiffness, a major risk factor for cardiovascular events. T, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) were measured longitudinally over 33 yr (follow-up 11.8 +/- 8.3 yr) in 901 men from the Baltimore Longitudinal Study of Aging, of whom 206 (68.1 +/- 13.7 yr) underwent carotid duplex ultrasonography. The 901 men were used to characterize age-associated hormone levels by means of mixed-effects models. Hormone values were estimated for the 206 men at the time of ultrasonography. Free T index (FTI) was calculated by dividing T by SHBG. The arterial stiffness index was calculated from peak systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure. T, FTI, and DHEAS were correlated negatively with age, pulse pressure (PP), and stiffness index (each P < 0.01), whereas SHBG was correlated positively with age and stiffness index (P < 0.01). However, T was the only hormone that predicted the stiffness index after adjustment for age, PP, fasting plasma glucose, body mass index, and total cholesterol. T values 5-10 yr before the carotid study also predicted the stiffness index (P < 0.05). Thus the adverse influence of low T on the cardiovascular system in men may be mediated in part via the effects of T on vascular structure and function.

Adult↗

PubMed2005

Arterial aging: is it an immutable cardiovascular risk factor?

Age is the dominant risk factor for cardiovascular diseases. However, until recently, convincing mechanistic or molecular explanations for the increased cardiovascular risks conferred by aging have been elusive. Aging is associated with alterations in a number of structural and functional properties of large arteries, including diameter, wall thickness, wall stiffness, and endothelial function. Emerging evidence indicates that these age-associated changes are also accelerated in the presence of cardiovascular diseases, and that these changes are themselves risk factors for the appearance or progression of these diseases. In this review, the evidence demonstrating that arterial aging is accelerated in cardiovascular diseases and that accelerated arterial aging is a risk factor for adverse cardiovascular outcomes is briefly reviewed, and selected advances in vascular biology that provide insights into the mechanisms that may underlie the increased risks conferred by arterial aging are summarized. Remarkably, a host of biochemical, enzymatic, and cellular alterations that are operative in accelerated arterial aging have also been implicated in the pathogenesis and progression of arterial diseases. These vascular alterations are thus putative candidates that could be targeted by interventions aimed at attenuating arterial aging, similar to the lifestyle and pharmacological interventions that have already been proven effective. Therefore, the notion that aging is a chronological process and that its risky components cannot be modulated is no longer tenable. It is our hope that a greater appreciation of the links between arterial aging and cardiovascular diseases will stimulate further investigation into strategies aimed at preventing or retarding arterial aging.

Aging↗

PubMed2005

Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults.

BACKGROUND: Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. METHODS AND RESULTS: aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. CONCLUSIONS: Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Aged↗

PubMed2005

apoE4 allele and the natural history of cardiovascular risk factors.

The aims of the present study were to compare the longitudinal changes in traditional cardiovascular (CV) risk factors (blood pressure, BMI, total and HDL-cholesterol, triglycerides, and blood glucose) in men with and without the apolipoprotein (apo)E4 allele. Three hundred six men from the Baltimore Longitudinal Study of Aging, ranging in age from 20 to 92 yr, were studied. Repeated measurements of CV risk factors were performed over a median follow-up time of 7 yr (maximum 14.3 yr) for men. Longitudinal changes in these CV risk factors were analyzed by linear mixed-effects models. The prevalence of the apoE4 allele was 25.5%. apoE4 was independently associated with accelerated changes over time in fasting plasma glucose (+9.5% vs. no change in those without apoE4 in the 6th age-decade over 10 yr). No significant effect of apoE4 on longitudinal changes in total or HDL-cholesterol, triglycerides, or blood pressures was observed. In conclusion, apoE4 influences fasting plasma glucose and its changes over time. This could explain, in part, the increased CV risk associated with the apoE4 genotype observed in men.

Adult↗

PubMed2005

Sex differences in left ventricular function in older persons with mild hypertension.

BACKGROUND: Epidemiologic studies suggest that women are at increased risk of developing heart failure secondary to hypertension. Other studies have documented sex differences in left ventricular systolic and diastolic function in the presence of pressure overload states such as seen in aortic stenosis and hypertension. It is less clear if sex differences are present among older persons with mild hypertension. METHODS: One hundred seven healthy subjects, aged 55 to 75 years, with blood pressures ranging from 130 to 159 mm Hg systolic and/or 85 to 99 mm Hg diastolic, were examined by standard echocardiography and the newer modalities of tissue Doppler and color M-mode imaging. RESULTS: Women had a lower peak mitral annular systolic velocity (Sm), 8.9 (95% CI 8.4-9.5) cm/s versus 10.2 (95% CI 9.6-11.0) cm/s, (P < .01) than men. Among women, increasing age was associated with a reduction in diastolic function. For every decade of age, peak early mitral annular diastolic velocity (Em) declined by 1.6 cm/s (P < .01), mitral inflow velocity of propagation (Vp) declined by 26% (P < .01), E/Vp ratio increased by 20% (P = .03), and E/Em ratio increased by 11% (P = .04) in women. No age-associated changes were seen in men. CONCLUSIONS: As revealed by newer echocardiographic imaging modalities, women with mild hypertension showed greater reductions in systolic and diastolic function as they aged compared with men. Our findings are consistent with the increased risk older women have of developing heart failure because of hypertension.

Age Factors↗

PubMed2005

The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the Cardiovascular Health Study.

OBJECTIVE: The prevalence of the metabolic syndrome, a potent risk factor for cardiovascular diseases (CVDs), has not been adequately explored in older individuals. Moreover, two sets of criteria have been proposed for the definition of metabolic syndrome, one by the World Health Organization (WHO) and one by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). We therefore investigated the prevalence of this syndrome in a subgroup of older participants from the Cardiovascular Health Study (CHS) who were free of CVD at baseline. We also compared the prognostic significance of the two definitions of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 2,175 subjects from the CHS who were free of CVD at baseline and not taking antihypertensive or lipid-lowering medications were studied. Prevalence of the metabolic syndrome was assessed with both the WHO and ATPIII criteria. The incidence of coronary or cerebrovascular disease was ascertained during a median follow-up time of 4.1 years. RESULTS: Prevalence of the metabolic syndrome was 28.1% by ATPIII criteria and 21.0% by WHO criteria. The two sets of criteria provided concordant classification for 80.6% of participants. Multivariate Cox propotional hazard models showed that the metabolic syndrome defined with the ATPIII criteria, but not with the WHO criteria, was an independent predictor of coronary or cerebrovascular events and was associated with a 38% increased risk (hazard ratio 1.38 [95% CI 1.06-1.79], P < 0.01). CONCLUSIONS: Prevalence of the metabolic syndrome in older individuals is approximately 21-28% (depending on the definition used). The two sets of criteria have 80% concordance in classifying subjects. As defined by the ATPIII criteria, the metabolic syndrome yields independent prognostic information, even after adjusting for traditional cardiovascular risk factors and the individual domains of the metabolic syndrome.

Aged↗

PubMed2005

Effects of a pharmacologically-induced shift of hemoglobin-oxygen dissociation on myocardial energetics during ischemia in patients with coronary artery disease.

BACKGROUND: Conventional strategies to treat myocardial ischemia include interventions that reduce oxygen demand and/or increase myocardial blood flow. Animal experiments suggest that right-shifting the hemoglobin-oxygen dissociation curve may also attenuate the metabolic consequences of myocardial ischemia. We evaluated whether exercise-induced myocardial ischemia can be alleviated in subjects with coronary artery disease (CAD) by enhancing oxygen release with an allosteric modifier of hemoglobin's affinity for oxygen (RSR13). METHODS AND RESULTS: Seven subjects with CAD underwent a randomized, double-blind, cross-over study of the metabolic consequences of RSR13 administration on myocardial ischemia. Myocardial high-energy phosphates were quantified with 31P nuclear magnetic resonance (NMR) spectroscopy before, during, and after isometric handgrip-exercise. Subjects underwent NMR studies at baseline and on two separate occasions following the infusion of RSR13 (100 mg/kg) or placebo. RSR13 infusion significantly increased mean p50 by 8.1 +/- 2.7 mmHg at the end of the infusion, and it was still elevated by 4.9 +/- 3.3 mmHg after the completion of the treadmill tests while placebo had no effect. The myocardial creatine-phosphate (PCr) to adenosine-triphosphate (ATP) ratio decreased during handgrip-exercise in the baseline studies (from 1.39 +/- 0.23 before exercise to 0.95 +/- 0.21 during handgrip-exercise, p = 0.0001) and in the placebo studies (from 1.29 +/- 0.16 to 0.98 +/- 0.37, p = 0.06) but not during administration of RSR13 (from 1.28 +/- 0.18 to 1.02 +/- 0.24, p = 0.12). However, the mean values of cardiac PCr/ATP during handgrip-exercise did not differ significantly among the three measurements (baseline, placebo, RSR13). CONCLUSIONS: A single infusion of RSR13 to subjects with CAD increased mean p50 by 4.9-8.1 mmHg but did not significantly alter myocardial PCr/ATP during exercise. This is the largest right-shift in hemoglobin-oxygen binding affinity achieved in CAD subjects, and it did not provide clear evidence of protection from cardiac ischemia.

Adenosine Triphosphate↗

PubMed2004

Age and gender affect ventricular-vascular coupling during aerobic exercise.

OBJECTIVES: The goal of this study was to examine the age-associated differences in ventricular-vascular coupling, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (E(LV)I), and its components, at rest and during exercise. BACKGROUND: Ejection fraction (EF) increases during exercise, but the EF reserve decreases with aging. Ejection fraction is inversely related to EaI/E(LV)I, an index of the interaction between arterial and ventricular properties, which is an important determinant of cardiac performance. Thus, age differences in EaI/E(LV)I during exercise, due to age differences in EaI, E(LV)I, or both, may help to explain the age deficit in EF reserve. METHODS: We noninvasively characterized EaI/E(LV)I = end-systolic volume index (ESVI)/stroke volume index (SVI) and its two determinants EaI = end-systolic pressure/SVI, and E(LV)I = end-systolic pressure/ESVI, at rest and during exercise in 239 healthy men and women (age range, 21 to 87 years). Blood pressures were assessed with cuff sphygomanometry, and cardiac volumes with gated blood pool scintingraphy. RESULTS: Resting EaI/E(LV)I was not age related in men or women. In both sexes, EaI/E(LV)I decreased during exercise and declined to a lesser extent in older subjects. There were gender differences in the components of EaI/E(LV)I during exercise: EaI was greater in older versus young women (p = 0.01) but was unaffected by age in men. Left ventricular systolic elastance increased to a greater extent in young versus older subjects (p = 0.0001 for men, p = 0.07 for women). CONCLUSIONS: Age-associated differences in EaI/E(LV)I occur in both genders during exercise. Sub-optimal ventricular-vascular coupling helps to explain the age-associated blunting of maximal exercise EF, and its underlying mechanisms appear to differ between men and women.

Adult↗

PubMed2004

Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness.

OBJECTIVES: We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND: Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS: Carotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS: The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS: Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties.

Adult↗

PubMed2004

Impaired glucose tolerance, but not impaired fasting glucose, is associated with increased levels of coronary heart disease risk factors: results from the Baltimore Longitudinal Study on Aging.

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) identify individuals at high risk for progression to diabetes. Whether IFG and IGT have comparable coronary heart disease (CHD) risk factor profiles, independent of their progression to diabetes, is unclear. We determined CHD risk factor levels in 937 nondiabetic individuals at baseline and biannually over a mean follow-up period of 9.5 years. Subjects had no known CHD at baseline and had > or =2 (mean 4.2) oral glucose tolerance tests during follow-up. We classified glucose tolerance categories using American Diabetes Association diagnostic criteria or modified criteria that redefined IFG as 100-126 mg/dl, creating a similar baseline prevalence of IFG and IGT. Subjects who developed diabetes during follow-up were excluded from our analysis. Baseline CHD risk factors were similar in subjects with normal glucose tolerance (NGT) and IFG, but significantly more atherogenic in those with IGT or IFG + IGT. These findings were unchanged when the modified criteria were used, suggesting that IGT is phenotypically different from IFG and is associated with increased levels of CHD risk factors. Subjects with isolated IFG had similar levels of CHD risk factors as NGT subjects, even when IFG was redefined with a lower threshold. Although CHD risk factors were increased in the IGT group, the incidence of CHD events was not significantly different among groups, perhaps owing to the limited number of events. The differences in CHD risk factors among prediabetic groups may have clinical implications for screening strategies and CHD risk stratification of individuals with IFG and IGT.

Adolescent↗