Biomedical subjects

G Heiss

Publications and source records attributed to G Heiss.

At least 37 records · Page 2Linked to original sources

PubMed2001

Genome-wide linkage analysis of lipids in the Hypertension Genetic Epidemiology Network (HyperGEN) Blood Pressure Study.

Full genome scans were performed for quantitative lipid measurements in 622 African American and 649 white sibling pairs not taking lipid-lowering medications who were ascertained through the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart, Lung, and Blood Institute (NHLBI) Family Blood Pressure Program. Genotypes for 391 markers spaced roughly equally throughout the genome were typed by the NHLBI Mammalian Genotyping Service. Each of the phenotypes was adjusted for covariates within sex and race and then subjected to variance components linkage analysis, which was performed separately within race by using race-specific marker allele frequencies from additional random samples. The highest lod score detected was 2.77 for logarithmically transformed triglyceride (TG) on chromosome 20 (at 28.6 cM) in the African American sibling pairs. The highest score detected in the white sibling pairs was 2.74 for high density lipoprotein cholesterol on chromosome 5 (at 48.2 cM). Although no scores >3.0 were obtained, positive scores were found in several regions that have been reported in other genome scans in the literature. For example, a score of 1.91 for TG was found on chromosome 15 (at 28.8 cM) in white sibling pairs. This score overlaps the positive findings for TG in 2 other genome scans.

Black People↗

PubMed2000

Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.

Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking.

Biomarkers↗

PubMed2000

Familial history of metabolic disorders and the multiple metabolic syndrome: the NHLBI family heart study.

UNLABELLED: A case-control study was conducted to investigate the association between family history of obesity, hypertension, and diabetes and the co-occurrence of metabolic disorders associated with the multiple metabolic syndrome (MMS). Included were 1,448 African and European American men and women aged 48-71 who participated in both the third cohort examination of the Atherosclerosis Risk in Communities study, 1992-1994, and phase I of the Family Heart Study 1993-1995. The joint occurrence of hypertension, dyslipidemia, and diabetes or impaired fasting glucose in an individual determined his/her status of "affected" (MMS: n = 97), while the absence of these three metabolic disorders determined his/her status of "unaffected" ( CONTROL: n = 527). First-degree relatives provided the information to calculate family risk scores (FRSs) for the phenotypes under study: obesity, diabetes and hypertension. Although the majority of cases were obese (76.3%), family history of obesity was associated only weakly with the MMS, while family history of diabetes, or hypertension was associated significantly with the MMS (controlling for age, race, gender, and sampling group). Obesity of cases and controls modified the strength of these associations-odds ratios were 2.5(95% CI:1.1-6.1) and 2.9(95% CI:1.2-7.0) for the diabetes and hypertension FRSs in the non-obese, while in obese individuals the respective odds ratios were 1.6(95% CI:0.9-2.8) and 1.7(95% CI:0.9-3.1). These results may imply that obesity, whether familial or environmental in nature, is associated with the development of the MMS, while in non-obese individuals a family history of diabetes, hypertension, or obesity is a marker of genetic predisposition to components of the MMS.

Aged↗

PubMed2000

Race and gender differences in cord blood lipoproteins.

Race and gender differences in lipoproteins and apolipoproteins have repeatedly been demonstrated in adults. The same disparities have been observed in children of different race and gender, implying that these differences may be influenced by genetic factors. To further explore this hypothesis, cord blood concentrations of both lipoproteins and apolipoproteins were examined in black and white neonates of both sexes. Results were controlled for the observed effects of gestational age and growth parameters. Similar patterns of lipoprotein differences to those observed in adults and children were also detected between black and white, and between male and female neonates. These findings support the concept that the aetiology of the difference in lipoprotein concentration observed between race and gender groups includes a significant genetic component.

Apolipoproteins↗

PubMed2000

Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease.

Cancer studies suggest that the null polymorphisms of glutathione S-transferase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has not been studied in humans. A case-cohort study was conducted to test the hypotheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n=400) accrued during 1987-1993 and a cohort-representative sample (n=924) were selected from a biracial cohort of 15792 middle-aged men and women in four US communities. A significantly higher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in whites (GSTM1-0=47.1%, GSTT1-0=16.4%) than in African-Americans (AAs) (GSTM1-0=17.5%, GSTT1-0=25.9%). A smoking-GSTM1-0 interaction for the risk of CHD was statistically significant on an additive scale, with ever-smokers with GSTM1-0 at a approximately 1.5-fold higher risk relative to ever-smokers with GSTM1-1 and a approximately 2-fold higher risk relative to never-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked >/=20 pack-years and GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and >/=20 pack-years of smoking was approximately three times greater than the risk given exposure to >/=20 pack-years of smoking alone, and approximately four times greater than the risk given exposure to GSTT1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT1 suggests that chemicals in cigarette smoke that are substrates for glutathione S-transferases may be involved in the etiology of CHD.

Case-Control Studies↗

PubMed2000

Haemostasis and carotid artery wall thickness in non-insulin dependent diabetes mellitus.

The purpose of this study was to examine the associations of carotid artery intima-media wall thickness (IMT) with hemostatic proteins and cardiovascular risk factors (CVRFs) in participants with and without non-insulin dependent diabetes mellitus (NIDDM). IMT measurements were determined by high resolution B-mode ultrasound imaging of the carotid arteries in 921 participants with NIDDM and 11,964 non-diabetic participants aged 45-64 years. Fasting glucose, serum lipids and activated partial thromboplastin time, factor VIII fibrinogen, factor VII, antithrombin III, protein C, and von Willebrand factor measurements were made. Compared to non-diabetic participants, participants with NIDDM had a more adverse pattern of CVRFs and a more procoagulatory profile. Participants with NIDDM had 0.06 mm (8.1%) higher mean IMT compared to non-diabetic participants after adjusting for age and gender (P < 0.001). However, only plasma fibrinogen concentrations showed statistically significant positive associations with IMT in both groups. After adjusting for CVRFs and fibrinogen, mean IMT remained 0.04 mm (5.4%) higher in diabetic compared to non-diabetic participants. Despite the more procoagulatory profile in participants with NIDDM, only plasma fibrinogen concentrations were independently associated with mean IMT. The association of NIDDM with mean IMT was only partly explained by CVRFs.

Age Distribution↗

PubMed2000

Hypertension and arterial stiffness: the Atherosclerosis Risk in Communities Study. ARIC Investigators.

Our objective was to describe the relationship of arterial stiffness and hypertension in a large, population-based sample of men and women. Hypertension-related increases in arterial stiffness may reflect the distending pressure and/or structural alterations in the artery. Included were 10,712 participants, ages 45 to 64 years, of the Atherosclerosis Risk in Communities Study, free of prevalent cardiovascular disease. Hypertension was classified as systolic or diastolic blood pressure (BP) > or =140/90 mm Hg, respectively, or the current use of antihypertensive medications. Common carotid arterial diameter change was measured using B-mode ultrasound and an electronic device that utilized radio frequency signals to track the motion of the arterial walls. Using statistical models to control for diastolic BP and pulse pressure, arterial diameter change was calculated separately in normotensive/ nonmedicated and medicated hypertensives. Hypertension was associated with a smaller adjusted diameter change (ie, greater stiffness) in comparison to optimal blood pressure (BP < 120/80 mm Hg): normotensive/nonmedicated men, 0.33 versus 0.43 mm (P < 0.001); medicated men, 0.34 versus 0.42 mm (P < 0.001); normotensive/ nonmedicated women, 0.34 versus 0.40 mm (P < 0.001), and medicated women, 0.33 versus 0.40 mm (P < 0.001). The relationship between pulse pressure and diameter change (ie, the slope of pulse pressure and diameter change) did not differ between hypertensives and normotensives. These cross-sectional data suggest that hypertension is associated with carotid arterial stiffness; however, these differences in the calculated stiffness appear to be the effect of distending pressure rather than structural changes in the carotid artery.

Age Distribution↗

PubMed2000

Association between the alpha-adducin gene and hypertension in the HyperGEN Study.

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the alpha-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that alpha-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the alpha-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.

Alleles↗

PubMed2000

NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network.

PURPOSE: Hypertension is a common precursor of serious disorders including stroke, myocardial infarction, congestive heart failure, and renal failure in whites and to a greater extent in African Americans. Large genetic-epidemiological studies of hypertension are needed to gain information that will improve future methods for diagnosis, treatment, and prevention of hypertension, a major contributor to cardiovascular morbidity and mortality. METHODS: We report successful implementation of a new structure of research collaboration involving four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six universities and the NHLBI who seek to identify and characterize genes promoting hypertension. Blood samples and clinical data were projected to be collected from a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships (half African-American) with two or more affected persons. Nonparametric sibship linkage analysis of over one million genotype determinations (20 candidate loci and 387 anonymous marker loci) was projected to have sufficient power for detecting genetic loci promoting hypertension. For loci showing evidence for linkage in this study and for loci reported linked or associated with hypertension by other groups, genotypes are compared in hypertensive cases versus population-based controls to identify or confirm genetic variants associated with hypertension. For some of these genetic variants associated with hypertension, detailed physiological and biochemical characterization of untreated adult offspring carriers versus non-carriers may help elucidate the pathophysiological mechanisms that promote hypertension. RESULTS: The projected sample size of 2244 hypertensive participants was surpassed, as 2407 hypertensive individuals (1262 African-Americans and 1145 whites) from 917 sibships were examined. Detailed consent forms were designed to offer participants several options for DNA testing; 94% of participants gave permission for DNA testing now or in the future for any confidential medical research, with only 6% requesting restrictions for tests performed on their DNA. Since this is a family study, participants also are asked to list all first degree relatives (along with names, addresses, and phone numbers) and to indicate for each relative whether they were willing to allow study staff to make a contact. Seventy percent gave permission to contact some relatives; about 30% gave permission to contact all first degree relatives; and less than 1% asked that no relatives be contacted. Successes after the first four years of this study include: 1) productive collaboration of eight centers from six different locations; 2) early achievement of recruitment goals for study participants including African-Americans; 3) an encouraging rate of consent for DNA testing (including future testing) and relative contacting; 4) completed analyses of genetic linkage and association for several candidate gene markers and polymorphisms; 5) completed genotyping of random markers for over half of the full sample; and 6) early sharing of results among the four Family Blood Pressure Program networks for candidate and genome search analyses. CONCLUSIONS: Experience after four years of this five-year program (1995-2000) suggests that the newly initiated NHLBI Network Program mechanism is fulfilling many of the expectations for which it was designed. It may serve as a paradigm for future genetic research that can benefit from large sample sizes, frequent sharing of ideas among laboratories, and prompt independent confirmation of early findings, which are required in the search for common genes with relatively small effects such as those that predispose to human hypertension.

Adult↗

PubMed2000

Fibrinogen, other putative markers of inflammation, and weight gain in middle-aged adults--the ARIC study. Atherosclerosis Risk in Communities.

PURPOSE: Weight gain is an important risk factor for the development of the metabolic syndrome, and inflammatory mediators are strongly associated with this syndrome. Our aim was to investigate whether inflammation predicts the development of weight gain in populations. RESEARCH METHODS AND PROCEDURES: We investigated selected markers of inflammation in the prediction of weight gain over an approximately 3-year period in a biethnic cohort of 13,017 men and women, 45 to 64 years of age, using multiple linear and logistic regression modeling. RESULTS: In adjusted models, those in the highest quartile of fibrinogen gained, during the first 3 years of follow-up, an estimated 0.23 kg/year more than those in the lowest quartile (p < 0.001). Adjusted odds of a large (greater than the 90th percentile) weight gain for those in the highest quartile of fibrinogen were 1.65 (95% confidence interval [CI], 1.38 to 1.97) times those in the lowest quartile. Similarly adjusted odds ratios for a large weight gain for those with high levels of white blood cell count, factor VIII, and von Willebrand factor were 1.38 (1.14 to 1.67), 1.28 (1.08 to 1.53), and 1.28 (1.08 to 1.51), respectively. DISCUSSION: Fibrinogen and other putative markers of inflammation predict weight gain in middle-aged adults. Given the known links between the inflammatory response and intermediary metabolism and the methodological strengths of the Atherosclerosis Risk in Communities (ARIC) cohort, these findings, though without immediate clinical applicability, suggest that inflammatory processes play a role in the development of the metabolic syndrome and cardiovascular disease in part through stimulation of weight gain.

Arteriosclerosis↗

PubMed2000

Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI family heart study.

OBJECTIVES: To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. DESIGN: A population-based cross-sectional study. SETTING: Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. SUBJECTS: All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. MAIN OUTCOME MEASURES: The prevalence of examined mutations by Lewis phenotype. RESULTS: The examined mutations were common and strongly associated with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). CONCLUSIONS: Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.

Arteriosclerosis↗

PubMed2000

Building bridges between populations and samples in epidemiological studies.

The increased use of rigorous population-sampling methods and the analysis of data from those samples in cross-sectional surveys, case-control studies, longitudinal-cohort investigations, and other epidemiological research efforts have raised important statistical issues for health analysts. We describe the origin, implications, and some plausible resolutions for several of these issues. Some of the main issues we consider include (a) establishing whom the sample represents; (b) using sample weights; (c) understanding the role of other important features, such as the use of sampling stratification and the selection of clustered groups of population members; and (d) finding ways to analyze study data with key sampling features in mind. Ultimately, resolution of all of these issues requires that analysts clearly define a reference population and then understand the role of design features in relating sample results to that population.

Bias↗

PubMed2000

Skip patterns in DINAMAP-measured blood pressure in 3 epidemiological studies.

Blood pressure measured by the oscillometric, automated device DINAMAP in 3 large population-based studies sponsored by the National Heart, Lung, and Blood Institute (The Atherosclerosis Risk in Communities Study, The Family Heart Study, and the Hypertension Genetic Epidemiology Network Study) were reviewed to determine an apparent skip pattern in the measurement values. Across the 3 studies, 2 different DINAMAP models were evaluated on >350 000 different blood pressure measurements. Measurements were taken in various positions, on both arm and ankles, and under various conditions (eg, resting and during stress). The following systolic blood pressure values were consistently skipped by the device: 89, 119, 120, 124, 125, 130, 140, 141, 150, 160, 170, 180, 190, and 200 mm Hg. No skip pattern was detected for diastolic blood pressure. Pulse data, which were only available in the Hypertension Genetic Epidemiology Network Study, also showed the following skipped values: 95, 99, 103, 106, and 109 bpm. Consultation with the manufacturer, the Critikon Corporation, indicated that the use of an algorithm designed to improve the accuracy of the DINAMAP device prevents these values from being displayed. Assessment of the extent and direction of bias caused by the skipped values is difficult, given that the algorithm is proprietary. While the implications of the skipped values are not clear, it is important for clinicians and researchers to be aware of this feature.

Blood Pressure↗

PubMed2000

Acute-phase inflammatory response to periodontal disease in the US population.

Moderate elevation of serum C-reactive protein (CRP) is a risk factor for cardiovascular disease among apparently healthy individuals, although factors that create this inflammatory response in the absence of systemic illness have not been clarified. This study aimed to: (1) evaluate associations among periodontal disease, established risk factors for elevated CRP, and CRP levels within the US population; and (2) determine whether total tooth loss is associated with reduced CRP. Data were obtained from the third National Health and Nutrition Examination Survey. A random sample of the US population was interviewed in their homes and examined at mobile examination centers. CRP was quantified from peripheral blood samples and analyzed as a continuous variable and as the prevalence of elevated CRP (> or = 10 mg/L). Some 12,949 people aged 18+ years who had periodontal examinations and an additional 1,817 edentulous people aged 18+ years were included in the analysis. Dentate people with extensive periodontal disease (> 10% of sites with periodontal pockets 4+ mm) had an increase of approximately one-third in mean CRP and a doubling in prevalence of elevated CRP compared with periodontally healthy people. Raised CRP levels among people with extensive periodontal disease persisted in multivariate analyses (P < 0.01), with established risk factors for elevated CRP (diabetes, arthritis, emphysema, smoking, and anti-inflammatory medications) and sociodemographic factors controlled for. However, CRP levels were similarly raised in edentulous people. Furthermore, the established risk factors for elevated CRP modified relationships between oral status and CRP levels. Periodontal disease and edentulism were associated with systemic inflammatory response in the US population, most notably among people who had no established risk factors for elevated CRP.

Acute-Phase Reaction↗

PubMed1999

Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.

BACKGROUND: Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes. METHODS: 12,330 men and women, aged 45-64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin. FINDINGS: 1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 (95% CI 1.6-2.3) for raised white-cell count, 1.3 (1.0-1.5) for low serum albumin, and 1.2 (1.0-1.5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 (2.6-23.7) and 3.7 (1.4-9.8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1.5 [1.3-1.8]), orosomucoid (7.1 [2.1-23.7]), and sialic acid (2.8 [1.0-8.1]) remained significant. INTERPRETATION: Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.

Autoimmunity↗

PubMed1999

Relative importance of various risk factors for asymptomatic carotid atherosclerosis versus coronary heart disease incidence: the Atherosclerosis Risk in Communities Study.

Major risk factors for coronary heart disease are also associated with early carotid artery thickening, but no studies have yet examined patterns of risk factors to see whether they differ for the two outcomes. Assuming similar pathogenesis for both coronary and carotid atherosclerosis, one could interpret risk factor pattern differences as relating to differences in staging, i.e., early atheroma versus later stenotic or occlusive atherothrombosis. This study included 12,193 Atherosclerosis Risk in Communities Study participants aged 45-64 years who were free of clinical cardiovascular disease in 1987-1989, in whom 420 myocardial infarctions or coronary heart disease deaths occurred over the next 6 years. Plasma low density lipoprotein cholesterol, systolic blood pressure, and smoking were major risk factors for both outcomes. Compared with these factors, triglycerides and high density lipoprotein (HDL) cholesterol were associated only weakly with carotid atherosclerosis but were associated strongly with coronary heart disease incidence. No other risk factors, including those associated with diabetes mellitus, hemostasis, and inflammation, differed in their relative contribution to the two outcomes. These results suggest that the high triglyceride-low HDL cholesterol pattern is involved in the transition from atheroma to atherothrombosis, and that control of this pattern may be important in persons with detectable subclinical disease.

Arteriosclerosis↗

PubMed1999

The relationship between lipids/lipoproteins and atherosclerosis in African Americans and whites: the Atherosclerosis Risk in Communities Study.

PURPOSE: The relationships between lipids/lipoproteins and atherosclerosis were determined in African Americans and whites to assess the consistency of the relationship between these two groups. Differences could suggest varying biological, environmental, or life-style cofactors influencing development of atherosclerosis. METHODS: In the Atherosclerosis Risk in Communities Study, 2966 African Americans and 9399 whites had determinations of LDL, HDL, HDL2, and HDL3 cholesterol, triglycerides, apolipoprotein A1 and B, and lipoprotein (a). Carotid intimal-medial thickening (IMT) was measured using B-mode ultrasound imaging. RESULTS: The associations, using linear regression, between carotid IMT and LDL cholesterol, HDL cholesterol, and other lipid measurements were significantly weaker in African Americans than whites. Averaging men and women, a 1.034 mmol/L (40 mg/dl) difference in LDL cholesterol was associated with a 0.028 mm IMT difference in whites but a 0.019 difference in African Americans. Similarly, for HDL cholesterol, a 0.44 mmol/L (17 mg/dl) difference is associated wth 0.026 mm difference in carotid IMT in whites and 0.011 mm difference in African Americans. The associations are much weaker in African Americans than whites at the bifurcation and internal carotid, the carotid sites most prone to atherosclerosis. Analysis was done stratifying for risk factors that differ between African Americans and whites, but within most, the relationships remained substantially weaker in African Americans. CONCLUSIONS: We have observed a statistically significant difference in the association between many lipids/lipoproteins and carotid IMT between African Americans and whites. Analysis of many potential cofactors have not provided an explanation for the weaker association. Although possible differences in prior levels of these lipids may provide one explanation for the finding, these results need confirmation in other studies.

Arteriosclerosis↗

PubMed1999

Evidence for a major gene accounting for mild elevation in LDL cholesterol: the NHLBI Family Heart Study.

Studies of rare Mendelian disorders of low density lipoprotein cholesterol (LDL-C) metabolism have identified specific genetic mutations in the LDL receptor and apolipoprotein B. Although these rare mutations account for a small proportion of LDL-C variation, twin and adoption studies indicate that at least 50% of the overall LDL-C observed variation is genetically determined. In a heterogeneous sample of 3227 subjects from the NHLBI Family Heart Study collected from four US centres, we find evidence for a common major gene accounting for mild elevations (1.25 standard deviations) in LDL-C. The analysis favored a recessive model with a frequency of 0.52 for the gene influencing elevated LDL-C, phenotypic means of 113 mg/dl for the normal genotypes and 146 mg/dl for the abnormal genotype, and a significant polygenic heritability. This statistically-inferred major gene accounted for 24% of the variation in LDL-C, with polygenes accounting for another 28% of the variation. Using parameters for major gene transmission estimated in the segregation analysis, LDL-C showed no linkage to the LDL receptor gene (LDLR), nor to the apolipoprotein E gene (APOE), nor to the cholesterol 7alpha-hydroxylase gene (CYP7A1), indicating the major gene effect influencing mild elevation in LDL-C is not explained by any of these candidate loci.

Adult↗