Biomedical subjects

G Heiss

Publications and source records attributed to G Heiss.

At least 19 recordsLinked to original sources

PubMed2006

Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

AIMS/HYPOTHESIS: To evaluate the role of oxidative stress and inflammation in the aetiology of type 2 diabetes, we examined the association of oxidised LDL (ox-LDL) and soluble intercellular adhesion molecule-1 (sICAM-1) levels with type 2 diabetes incidence over 9 years in the Atherosclerosis Risk in Communities Study. MATERIALS AND METHODS: In a large, prospective, case-cohort design, ox-LDL and sICAM-1 were measured in stored plasma samples collected at baseline in stratified samples of 581 diabetes cases and 572 non-cases selected from 10,275 middle-aged men and women without prevalent diabetes at baseline. RESULTS: Compared with non-cases, diabetes cases had significantly higher mean baseline levels of ox-LDL and sICAM-1. Elevated ox-LDL and sICAM-1 were both associated with increased risk of incident diabetes after adjustment for age, sex, race and centre, with hazard ratios for the highest vs lowest tertiles of 1.68 (95% CI 1.25-2.24) and 1.91 (95% CI 1.45-2.50), respectively. After additional adjustment for fasting glucose, waist circumference, HDL-cholesterol, triacylglycerol, hypertension and C-reactive protein, only sICAM-1 remained an independent predictor of incident diabetes (hazard ratio 1.50; 95% CI 1.02-2.23). CONCLUSIONS/INTERPRETATION: In this community-based cohort of middle-aged US adults, elevated plasma ox-LDL and sICAM-1 levels were associated with increased risk of type 2 diabetes. Measurement of ICAM-1 or ox-LDL, or other measures related to inflammation or oxidative stress, may be helpful in identifying those patient populations in which to test whether novel therapies that inhibit specific pathways related to inflammation or oxidative stress are beneficial in the prevention of diabetes in humans.

Black or African American↗

PubMed2006

QTL-specific genotype-by-smoking interaction and burden of calcified coronary atherosclerosis: the NHLBI Family Heart Study.

BACKGROUND: Calcified coronary plaque (CCP) is a complex trait influenced by both genes and environment, and plausibly an interaction between the two. Because the familial aggregation of CCP has been demonstrated and smoking is a significant, independent predictor of CCP, we assessed the evidence for genotype-by-smoking interaction and conducted linkage analysis of quantitative Agatston CCP scores in participants of the NHLBI Family Heart Study (FHS). METHODS: During standardized clinical exams smoking habits were ascertained and CCP was quantified with cardiac computed tomography (CT). Among 4387 relationship pairs from 2128 Caucasian examinees variance component analysis was implemented in SOLAR to examine: (1) additive genotype-by-smoking status interaction using a variance component approach; (2) linkage analysis in the full sample and among smoking subsets defined by individual smoking exposure; (3) QTL-specific genotype-by-smoking interaction in the regions that appeared to differentiate between smoking strata. RESULTS: The prevalence of CCP (and median Agatston score) was 75% (184.6) in men and 48% (51.0) in women. We detected four genome-wide significant logarithm of odds (LOD) scores in samples stratified by individual smoking exposure: chromosome 4 at 122cM (nearest marker D4S2297; robust adjusted LOD=3.1; q=0.053), chromosome 6 at 99cM (nearest marker D6S1056; robust adjusted LOD=3.3; q=0.053), chromosome 11 at 19cM (nearest marker D11S199; robust adjusted LOD=4.0; q=0.02) and chromosome 13 at 77cM (nearest marker D13S892; robust adjusted LOD=3.1; q=0.053). Additive and QTL-specific genotype-by-smoking interaction was detected on chromosomes 4, 6, 11 and 13; all P<0.05. Three of the four QTLs identified in this report have been previously linked to atherosclerosis and harbor interesting candidate genes. CONCLUSIONS: These findings demonstrate the importance of considering complex interactions in the search for genes that influence the pathogenesis of CCP.

Adult↗

PubMed2006

Leptin and incident type 2 diabetes: risk or protection?

AIMS/HYPOTHESIS: The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance. SUBJECTS AND METHODS: We conducted a case-cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA. RESULTS: In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6-5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23-0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32-1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both). CONCLUSIONS/INTERPRETATION: High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin's described protective effects against diabetes.

Adiponectin↗

PubMed2006

The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial.

AIMS/HYPOTHESIS: Recent clinical trials have found that the combination of conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect on the incidence of type 2 diabetes. To determine the effect of CEO alone on the incidence of diabetes mellitus in postmenopausal women, we analysed the results of the Women's Health Initiative oestrogen-alone trial. METHODS: The Women's Health Initiative is a randomised, double-masked trial comparing the effect of daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739 postmenopausal women who were aged 50-79 years and had previously had a hysterectomy. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin and lipoproteins were measured in an 8.6% random sample of study participants, at baseline and at 1, 3 and 6 years. RESULTS: The cumulative incidence of treated diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow-up, a significant fall in insulin resistance (homeostasis model assessment of insulin resistance) in actively treated women compared with the control subjects (Year 1 baseline between-group difference -0.53) was seen. However, there was no difference in insulin resistance at the 3- or 6-year follow-up. CONCLUSIONS/INTERPRETATION: Postmenopausal therapy with oestrogen alone may reduce the incidence of treated diabetes. The effect is smaller than that seen with oestrogen plus progestin. CEO should not, however, be used with the intention of preventing diabetes, as its well-described adverse effects preclude long-term use for primary prevention.

Aged↗

PubMed2005

Genome-wide scans for heritability of fasting serum insulin and glucose concentrations in hypertensive families.

AIMS/HYPOTHESIS: The heritability of fasting serum insulin and glucose concentrations in non-diabetic members of multiplex hypertensive families is unknown. METHODS: We calculated the familial aggregation of fasting serum glucose and insulin concentrations and performed a genome-wide scan to assess whether quantitative trait loci contribute to these phenotypes in 2,412 non-diabetic individuals from 1,030 families enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN) in the Family Blood Pressure Program. RESULTS: The heritability (+/-SE) of fasting serum insulin was 0.47+/-0.085 in European Americans and 0.28+/-0.08 in African Americans (p<0.0001 for both), after adjusting for age, sex, and BMI. A genome-wide scan for fasting serum insulin yielded a maximum log of the odds (LOD) score of 2.36 on chromosome 5 at 20 cM (p=0.0004) in European Americans, and an LOD score of 2.28 on chromosome 19 at 11 cM (p=0.0004) in African Americans. The heritability of fasting serum glucose was 0.5109+/-0.08 in the former and 0.29+/-0.09 in the latter (p<0.0003 for both) after adjusting for age, sex and BMI. A genome-wide scan for fasting serum glucose revealed a maximum LOD score of 2.07 on chromosome 5 at 26 cM (p=0.0009) in European Americans. CONCLUSIONS/INTERPRETATION: These analyses demonstrate the marked heritability of fasting serum insulin and glucose concentrations in families enriched for the presence of members with hypertension. They suggest that genes associated with fasting serum insulin concentration are present on chromosomes 19 and 5, and that genes associated with fasting serum glucose concentration are on chromosome 5, in families enriched for hypertension.

Adult↗

PubMed2004

Association of the Lewis genotype with cardiovascular risk factors and subclinical carotid atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVES: To evaluate the relationship of Lewis genotypes with major cardiovascular risk factors and the intima-media thickness (IMT) of carotid arteries. Lewis genotyping included four major mutations of the Lewis (FUT3) gene at nucleotide positions 59, 1067, 202 and 314. DESIGN: Two complementary population-based cross-sectional studies. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. SUBJECTS: The relationship between Lewis genotype and major cardiovascular risk factors was studied in 761 men and women aged 45-64 years without known clinical atherosclerotic disease; 577 were Caucasians and 184 were African-Americans. The association of Lewis genotype and subclinical carotid atherosclerosis was studied in 419 individuals with, and 819 controls without carotid IMT of >1.0 mm, measured by B-mode ultrasound. MAIN OUTCOME MEASURES: Mean values of cardiovascular risk factors by Lewis genotype. Lewis genotype frequencies in subclinical carotid atherosclerosis cases and controls. RESULTS: Individuals with Lewis genotypes consistent with lack of alpha(1,3/1,4)-fucosyltransferase activity (i.e. Lewis-negative genotype) had statistically significantly lower fasting glucose, factor VIIIc, von Willebrand factor and diastolic blood pressure compared with their counterparts with Lewis-positive genotypes. The distribution of Lewis genotypes and haplotypes was not significantly different between individuals with carotid IMT of >1.0 mm (cases) and their controls. The odds of carotid atherosclerosis in carriers of the Lewis-negative genotype was 1.23 (95% confidence interval 0.70-2.16) compared to individuals with Lewis-positive genotype, controlling for age, gender and race/ARIC field centre. CONCLUSION: The lack of a statistically significant association between Lewis 'genotype' and subclinical atherosclerosis in our data suggests that earlier studies reporting associations at the 'phenotypic' level may reflect aspects of the biology of the Lewis system other than an inherent genetic property.

Blood Pressure↗

PubMed2002

Distribution of Lewis (FUT3)genotype and allele: frequencies in a biethnic United States population.

The objective of the study was to examine the prevalence and distribution of four major single nucleotide polymorphisms (SNPs) (T59G, T1067G, T202C, and C314T) of the Lewis ( FUT3)gene in a biethnic United States population. This population-based cross-sectional study was based on data from the Atherosclerosis Risk in Communities (ARIC) Study, which included 761 males and females aged 45-64 years, who had no known/detected clinical atherosclerotic disease (577 Caucasians, 184 African Americans). The main outcome measures were prevalence of the Lewis genotype and allele frequencies for four SNPs of the FUT3gene. The most common genotype was the "wild type" at all four nucleotide positions ( WWWW), which was found to be present in 46.9% of ARIC participants. At least one mutant allele was detected in 51.7% of Caucasians, and 56.7% of African Americans ( P=0.59). The frequencies of mutant alleles ranged from 6.3% to 18.4% at the four FUT3gene sites examined. The distribution of the Lewis genotype and allele frequencies differed significantly by ethnicity at sites 59, 202, and 314. The prevalence of the Lewis genotype suggesting a lack of alpha(1,3/1,4) fucosyltransferase activity was 11.6% in Caucasians and 9.9% in African Americans ( P=0.67). Four specific SNPs of the Lewis genotype are common in the population at large. However, these four SNPs seem to fail to explain the majority of Lewis-negative phenotype in African Americans, given that Lewis-negative genotype prevalence was about one-third of what was expected. Use of rapid DNA sequencing and simultaneous Lewis phenotype determination could avoid the problems associated with haplotype determination and Lewis genotype grouping. Further studies testing SNPs of the Lewisgene are warranted, in particular among African Americans.

Age Factors↗

PubMed2002

Association between the blood pressure response to a change in posture and the 6-year incidence of hypertension: prospective findings from the ARIC study.

The association between the blood pressure response to a change from the supine to the standing position and the 6-year incidence of hypertension was studied in a bi-ethnic, middle-aged cohort of 6951 normotensive men and women free of coronary heart disease at baseline. Postural change in systolic blood pressure (SBP) was categorized into deciles, and the middle four deciles served as the referent (no change) group. In unadjusted analyses, the incidence of hypertension was higher among both those with SBP increases and decreases relative to those in the referent group. Associations were modestly attenuated after controlling for age, ethnicity, and gender and cardiovascular disease risk factors. However, after adjustment for baseline, seated SBP, a modest association with incident hypertension persisted only for SBP decreases. Orthostatic hypotension (upon standing) was associated with incident hypertension and isolated systolic hypertension and, unexpectedly, this increased risk was highest among those with the lowest levels of baseline, resting SBP.

Cohort Studies↗

PubMed2001

Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. METHODS AND RESULTS: After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins (apo) A-I or B. Despite strong univariate associations, apoB did not contribute to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high apoB relative to LDL-C. CONCLUSIONS: Optimal LDL-C values are <100 mg/dL in both women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.

Apolipoprotein A-I↗

PubMed2001

Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: the NHLBI family heart study.

Decreased serum bilirubin levels have been associated with coronary heart disease (CHD). It is believed that bilirubin acts as an antioxidant, preventing formation of oxidized LDL and subsequent atherosclerosis. Serum bilirubin also segregates as a major gene, with the rarer genotype associated with elevated bilirubin levels and occurring in about 12% of the population. Using a large population-based study of random and CHD high risk families, this analysis was designed to replicate the association of lower serum bilirubin levels with early CHD (onset by age 55 for males and 65 for females) using 328 case/control samples and the major gene segregation of bilirubin levels in 555 families. There were significant differences in plasma bilirubin levels between 188 males (12.5 micromol/l) and 140 females (9.3 micromol/l, P<0.0001). Higher serum albumin and lower HDL-C significantly correlated with higher plasma bilirubin levels in females but not males. In sex-specific logistic regression models of early CHD (148 cases and 180 controls), lower plasma bilirubin was associated with increased prevalence of CHD in males with borderline significance (odds ratio=0.93 for a 1 micromol/l increase in bilirubin, P=0.056) but not in females. Bilirubin was found to segregate as a major gene using all 555 families consisting of 1292 individuals, with estimates replicating those in the previously published study. The most parsimonious model was a recessive model for high bilirubin levels that occurred in about 23% of the population. The means were separated by 1.7 standard deviations and there was a significant polygenic effect (h2=0.33, P=0.0009). We conclude that decreased bilirubin is mildly related to CHD in males but not in females. Because of an inverse correlation between HDL-C and bilirubin, the protective high HDL-C levels may have counteracted the CHD risk associated with lower bilirubin levels in females. The inferred major gene for bilirubin may protect against CHD, since elevated levels, rather than lower levels, were associated with this inferred gene.

Aged↗

PubMed2001

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Adult↗

PubMed2001

Association of ventricular premature complexes with electrocardiographic-estimated left ventricular mass in a population of African-American and white men and women (The Atherosclerosis Risk in Communities.

Increased left ventricular (LV) mass is often found in adults and is a powerful predictor of cardiovascular mortality. To test the hypothesis that an electrocardiographic estimate of LV mass--the Cornell voltage--is associated with ventricular premature complexes (VPCs) in free-living adults, a cross-sectional analysis of the predictors of VPCs on a 2-minute rhythm strip in a population-based sample of 13,606 middle-aged, African-American and white men and women from 4 US communities in the Atherosclerosis Risk in Communities Study baseline examinations was performed. In adults without known coronary artery disease, the prevalence of VPCs increases monotonically with increasd Cornell voltages within ethnicity and gender groups. Independent of systemic hypertension, serum electrolytes, age, heart rate, educational attainment, gender, and ethnicity, a millivolt increase in Cornell voltage was associated with a 20% to 30% increase in the prevalence odds ratio of VPCs on the 2-minute electrocardiogram. Thus, Cornell voltage is associated with VPCs on a 2-minute electrocardiogram. The association is consistent in African-Americans, whites, men, and women.

Aged↗

PubMed2001

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts CHD.

The relationship between carotid artery lesions (CALs), with and without acoustic shadowing (AS) as an index of arterial mineralization, and incident coronary heart disease (CHD) was examined in the Atherosclerosis Risk in Communities study cohort. Among 12,375 individuals, ages 45-64 years, free of CHD at baseline, 399 CHD events occurred between 1987-1995. In a 3-cm segment centered at the carotid bifurcation, CALs with and without AS were identified by B-mode ultrasound (US). After adjustment for the major CHD risk factors, the CHD hazard ratio (HR) for women with CAL without AS compared to women without CAL was 1.78 (95% CI: 1.22, 2.60) and the HR comparing women with CAL with AS to women with CAL without AS was 1.73 (95% CI: 1.07, 2.80). Corresponding HRs for men were 1.59 (95% CI: 1.22, 2.07) and 1.04 (95% CI: 0.72, 1.51). CALs predicted CHD events; this association was stronger for mineralized CALs in women, but not men.

Calcinosis↗

PubMed2001

Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study.

Despite the reported association of lipoprotein responses to a fatty meal with atherosclerosis, little is known about the determinants of these responses. Plasma triglyceride, retinyl palmitate, and apolipoprotein B-48 responses to a standardized fatty meal containing a vitamin A marker were measured in 602 Atherosclerosis Risk in Communities (ARIC) study participants. To focus on postprandial responses specifically, which have been reported to be related to atherosclerosis independently of fasting triglycerides, analyses for determinants of postprandial responses were adjusted for fasting triglycerides. Major determinants of fasting triglycerides, namely, diabetes, obesity, other factors related to insulin resistance, and male sex, were not independently associated with postprandial responses. Fasting triglycerides were the strongest predictor of postprandial lipids, but independent of triglycerides, the predictors of postprandial responses were smoking, diet, creatinine, and alcohol. Smokers had substantially increased retinyl palmitate and apolipoprotein B-48 responses, indicators of chylomicrons and their remnants. Persons who consume more calories or omega3 fatty acids had reduced chylomicron responses. Triglyceride responses were associated positively with serum creatinine levels and negatively with moderate alcohol consumption. Thus, determinants of fasting and postprandial lipids differ. The independent atherogenic influence of postprandial lipids may relate more to smoking and diet than to obesity and insulin resistance.

Aged↗

PubMed2001

Alcohol consumption and the incidence of hypertension: The Atherosclerosis Risk in Communities Study.

A close relationship between alcohol consumption and hypertension has been established, but it is unclear whether there is a threshold level for this association. In addition, it has infrequently been studied in longitudinal studies and in black people. In a cohort study, 8334 of the Atherosclerosis Risk in Communities (ARIC) Study participants, aged 45 to 64 years at baseline, who were free of hypertension and coronary heart disease had their blood pressures ascertained after 6 years of follow-up. Alcohol consumption was assessed by dietary interview. The type of alcoholic beverage predominantly consumed was defined by the source of the largest amount of ethanol consumed. Incident hypertension was defined as a systolic blood pressure >/=140 mm Hg or diastolic blood pressure >/=90 mm Hg or use of antihypertensive medication. There was an increased risk of hypertension in those who consumed large amounts of ethanol (>/=210 g per week) compared with those who did not consume alcohol over the 6 years of follow-up. The adjusted odds ratios (95% confidence interval) were 1.2 (0.85 to 1.67) for white men, 2.02 (1.08 to 3.79) for white women, and 2.31 (1.11 to 4.86) for black men. Only 4 black women reported drinking >210 g ethanol per week. At low to moderate levels of alcohol consumption (1 to 209 g per week), the adjusted odds ratios (95% confidence interval) were 0.88 (0.71 to 1.08) in white men, 0.89 (0.73 to 1.09) in white women, 1.71 (1.11 to 2.64) in black men, and 0.88 (0.59 to 1.33) in black women. Systolic and diastolic blood pressures were higher in black men who consumed low to moderate amounts of alcohol compared with the nonconsumers but not in the 3 other race-gender strata. Models with polynomial terms of alcohol exposure suggested a nonlinear association in white and black men. Higher levels of consumption of all types of alcoholic beverages were associated with a higher risk of hypertension for all race-gender strata. The consumption of alcohol in amounts >/=210 g per week is an independent risk factor for hypertension in free-living North American populations. The consumption of low to moderate amounts of alcohol also appears to be associated with a higher risk of hypertension in black men.

Alcohol Drinking↗

PubMed2001

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. METHODS: The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986-1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound-detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation. RESULTS: The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men. CONCLUSIONS: B-mode ultrasound-detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.

Brain Ischemia↗

PubMed2001

Relationship of periodontal disease to carotid artery intima-media wall thickness: the atherosclerosis risk in communities (ARIC) study.

Periodontitis has been linked to clinical cardiovascular disease but not to subclinical atherosclerosis. The purpose of this study was to determine whether periodontitis is associated with carotid artery intima-media wall thickness (IMT). Cross-sectional data on 6017 persons aged 52 to 75 years were obtained from the Atherosclerosis Risk in Communities Study 1996 to 1998 examination. The dependent variable was carotid IMT >/=1 mm. Periodontitis was defined by extent of attachment loss >/=3 mm: none/mild (<10%), moderate (10% to <30%), or severe (>/=30%). Covariates included age, sex, diabetes, LDL cholesterol, HDL cholesterol, triglycerides, hypertension, smoking, waist-hip ratio, education, and race/study center. Odds of IMT >/=1 mm were higher for severe periodontitis (OR 2.09, 95% CI 1.73 to 2.53) and moderate periodontitis (OR 1.40, CI 1.17 to 1.67) compared with no periodontitis. In a multivariable logistic regression model, severe periodontitis (OR 1.31, CI 1.03 to 1.66) was associated with IMT >/=1 mm, while adjusting for the other factors in the model. These results provide the first indication that periodontitis may play a role in the pathogenesis of atheroma formation, as well as in cardiovascular events.

Arteriosclerosis↗

PubMed2001

Genome scan for quantitative trait loci linked to high-density lipoprotein cholesterol: The NHLBI Family Heart Study.

We conducted a genome-wide linkage scan for quantitative trait loci influencing total HDL-cholesterol (HDL-C) concentration in a sample of 1027 whites from 101 families participating in the NHLBI Family Heart Study. To maximize the relative contribution of genetic components of variance to the total variance of HDL-C, the HDL-C phenotype was adjusted for age, age(2), body mass index, and Family Heart Study field center, and standardized HDL-C residuals were created separately for men and women. All analyses were completed by the variance components method, as implemented in the program GENEHUNTER using 383 anonymous markers typed at the NHLBI Mammalian Genotyping Service in Marshfield, Wis. Evidence for linkage of residual HDL-C was detected near marker D5S1470 at location 39.9 cM from the p-terminal of chromosome 5 (LOD=3.64). Suggestive linkage was detected near marker D13S1493 at location 27.5 cM on chromosome 13 (LOD=2.36). We conclude that at least 1 genomic region is likely to harbor a gene that influences interindividual variation in HDL cholesterol.

Adolescent↗