Biomedical subjects

A Richey Sharrett

Publications and source records attributed to A Richey Sharrett.

At least 19 recordsLinked to original sources

PubMed2007

The association of the ankle-brachial index with incident coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001.

BACKGROUND: Peripheral arterial disease (PAD), defined by a low ankle-brachial index (ABI), is associated with an increased risk of cardiovascular events, but the risk of coronary heart disease (CHD) over the range of the ABI is not well characterized, nor described for African Americans. METHODS: The ABI was measured in 12186 white and African American men and women in the Atherosclerosis Risk in Communities Study in 1987-89. Fatal and non-fatal CHD events were ascertained through annual telephone contacts, surveys of hospital discharge lists and death certificate data, and clinical examinations, including electrocardiograms, every 3 years. Participants were followed for a median of 13.1 years. Age- and field-center-adjusted hazard ratios (HRs) were estimated using Cox regression models. RESULTS: Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95% CI) for PAD (ABI<0.90) was 2.81 (1.77-4.45) for men and 2.05 (1.20-3.53) for women. In African Americans, the HR for men was 4.86 (2.76-8.47) and for women was 2.34 (1.26-4.35). The CHD risk increased exponentially with decreasing ABI as a continuous function, and continued to decline at ABI values > 1.0, in all race-gender subgroups. The association between the ABI and CHD relative risk was similar for men and women in both race groups. A 0.10 lower ABI increased the CHD hazard by 25% (95% CI 17-34%) in white men, by 20% (8-33%) in white women, by 34% (19-50%) in African American men, and by 32% (17-50%) in African American women. CONCLUSION: African American members of the ARIC cohort had higher prevalences of PAD and greater risk of CHD associated with ABI-defined PAD than did white participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at high (>1.3) ABI values. We conclude that at this time high ABI values should not be routinely considered a marker for increased CVD risk in the general population. Further research is needed on the value of the ABI at specific cutpoints for risk stratification in the context of traditional risk factors.

Black or African American↗

PubMed2007

LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Previous studies showing that smaller low-density lipoprotein (LDL) size is associated with greater atherosclerotic risk did not adequately control for small and large LDL particle correlation. METHODS AND RESULTS: We studied the association of lipoproteins measured by proton nuclear magnetic resonance spectroscopy with carotid intima-media thickness (IMT) in apparently healthy individuals (N = 5538, 38% White, 28% African American, 22% Hispanic, 12% Chinese). Small and large LDL particle concentrations (LDL-p) were inversely correlated (r = /-0.63, P < 0.0001). Controlling for risk factors but not for LDL subclass correlation, LDL size and small LDL-p separately were associated with IMT (-20.9 and 31.7 microm change in IMT per 1-S.D., respectively, both P < 0.001), but large LDL-p was not (4.9 microm, P = 0.27). When LDL subclasses were included in the same model, large and small LDL-p were both associated with IMT (36.6 and 52.2 microm higher IMT per 1-S.D., respectively, both P < 0.001; 17.7 and 11.6 microm per 100 nmol/L, respectively). LDL size was not significant after accounting for LDL subclasses and risk factors (P = 0.10). CONCLUSION: Both LDL subclasses were significantly associated with subclinical atherosclerosis, with small LDL confounding the association of large LDL with atherosclerosis. Future studies of LDL size should account for the strong inverse correlation of LDL subclasses.

Aged↗

PubMed2007

Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine the association of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and all-cause mortality. DESIGN: Population-based prospective cohort study. PARTICIPANTS: From the Atherosclerosis Risk in Communities Study (n = 12 536; age range, 49-73 years). METHODS: Participants had retinal photographs of one eye taken between 1993 and 1995. Photographs were evaluated for the presence of early and late AMD signs according to the Wisconsin grading system. Incident CHD events (acute myocardial infarction, silent myocardial infarction, fatal CHD, and cardiac revascularization procedures) and all-cause mortality were identified prospectively using standardized methods. MAIN OUTCOME MEASURES: Incident CHD events and all-cause mortality. RESULTS: Of 11,414 persons at risk of CHD, there were 555 (4.9%) with AMD at baseline, of whom 540 were early AMD and 15 were late AMD cases. Over a 10-year follow-up, 922 persons developed an incident CHD event. After controlling for age, gender, race, systolic and diastolic blood pressure, pack-years of cigarette smoking, and other variables, early AMD was not associated with incident CHD (relative risk, 1.08; 95% confidence interval, 0.82-1.42). However, individuals with late AMD were significantly more likely to have an incident CHD event, with 4 CHD events among the 15 participants with late AMD at baseline (10-year cumulative incidence, 30.9%) as compared with 918 CHD events among the 11 399 participants without late AMD (incidence of 10.0%; P = 0.049, Fisher exact test). In the full cohort (n = 12 536), early AMD was not significantly associated with all-cause mortality. However, individuals with late AMD were more likely to die (10-year cumulative mortality rate, 23.5%) than those without late AMD (mortality rate, 8.9%; P = 0.088, Fisher exact test). CONCLUSIONS: These data provide no evidence of an association between early AMD signs with incident CHD and all-cause mortality in middle-aged persons. Individuals with late AMD appear to have a higher rate of CHD events than those without late AMD, but due to a small number of late AMD cases, this finding should be interpreted cautiously.

Aged↗

PubMed2007

Measurement of retinal vascular caliber: issues and alternatives to using the arteriole to venule ratio.

PURPOSE: The arteriole to venule ratio (AVR) is widely used in studies of the associations of retinal microvascular disease with systemic and ocular outcomes. This is a discussion of the limitations of AVR; a comparison of its predictive information with that of its components, arteriolar and venular caliber; and a description of a suggested alternative method of modeling arteriolar and venular calibers directly. METHODS: Data from the population-based Blue Mountains Eye Study were used to compare the predictive information in models using AVR with models using arteriolar and venular calibers directly. Determination was made of how the apparent relationship between vessel caliber and two systemic outcomes (blood pressure [BP] and white blood cell count [WBC]) was influenced by the choice of regression model. These findings were interpreted with reference to the known biological relationship among vessel calibers, BP, and WBC. RESULTS: Models using arteriolar and venular calibers directly had more predictive information than models using AVR. The apparent relationship of vessel caliber to BP and WBC differed substantially, depending on the model chosen. For example, after adjustment for age, sex, and other covariates, decreasing venular caliber was associated with higher systolic BP when modeled separately, but was associated with lower systolic BP when modeled simultaneously with arteriolar caliber. CONCLUSIONS: The findings suggest AVR provides less information with regards to predicting systemic outcomes than its two components. Modeling arteriolar and venular calibers separately could be biased by confounding, while modeling both simultaneously appears to provide unbiased, biologically plausible results. The use of this approach is recommended in future research relating retinal vascular caliber to systemic or ocular outcomes.

Aged↗

PubMed2006

Is diabetic retinopathy an independent risk factor for ischemic stroke?

BACKGROUND AND PURPOSE: The relationship between diabetic retinopathy and ischemic stroke is uncertain and examined in this study. METHODS: A population-based, prospective cohort study of 1617 middle-aged persons with diabetes. Diabetic retinopathy signs were ascertained from retinal photographs, and incident ischemic stroke events were prospectively identified and validated. RESULTS: Over an average follow-up of 7.8 years, there were 75 ischemic stroke events. After adjustment for age, gender, race, center, 6-year mean arterial blood pressure, anti-hypertensive treatment use, fasting glucose, insulin treatment, duration of diabetes, high-density lipoprotein and low-density lipoprotein cholesterol levels and cigarette smoking status, diabetic retinopathy was associated with an increased risk of ischemic stroke (hazard rate ratio, 2.34; 95% CI, 1.13 to 4.86). CONCLUSIONS: Diabetic retinopathy predicts incident ischemic stroke in people with diabetes, independent of other risk factors.

Brain Ischemia↗

PubMed2006

Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

Aged↗

PubMed2006

Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study.

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.

Age Factors↗

PubMed2006

The effect of novel cardiovascular risk factors on the ethnic-specific odds for peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: The purpose of this study was to: 1) determine the significance and magnitude of associations between novel cardiovascular disease (CVD) risk factors and peripheral arterial disease (PAD) after adjustment for traditional risk factors; and 2) ascertain the extent to which novel risk factors explain the excess or lower risk for PAD in different ethnic groups. BACKGROUND: Previous reports have found a significant difference in the risk of PAD by ethnic group, with some of the risk difference attributed to different levels of traditional CVD risk factors. METHODS: A total of 6,814 individuals free of clinically apparent CVD were enrolled in the MESA (Multiethnic Study of Atherosclerosis) and underwent standardized testing for the presence of PAD by the ankle-brachial index. These subjects also had fasting blood drawn for serum cholesterol, glucose, and a number of novel biomarkers for CVD. Non-Hispanic whites were the largest ethnic group (38%), followed by African Americans (28%), Hispanics (22%), and Chinese (12%). RESULTS: In this cross-sectional analysis, 6,653 subjects with an ankle brachial index <1.40 were analyzed. The mean (SD) age was 62.2 (10.2) years, and 52.9% were women. Interleukin-6, fibrinogen, D-dimer, and homocysteine were significantly associated with PAD after adjustment for traditional CVD risk factors. Compared with non-Hispanic whites and after adjustment for traditional and "novel" risk factors, the odds for PAD were 1.47 (95% confidence interval [CI]: 1.07 to 2.02) times higher in African Americans, while being 0.45 (95% CI: 0.29 to 0.70) and 0.44 (95% CI: 0.24 to 0.78) in Hispanics and Chinese, respectively. CONCLUSIONS: Ethnic associations with PAD remained significant even after adjustment for traditional and novel risk factors. This suggests that unknown factors may account for the residual ethnic differences in PAD.

Black or African American↗

PubMed2006

Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. METHODS AND RESULTS: We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987-1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0; 95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6). CONCLUSIONS: OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Age Factors↗

PubMed2006

Age-related macular degeneration and risk for stroke.

BACKGROUND: Age-related macular degeneration (AMD) affects 7 million persons 40 years of age and older in the United States. Risk factors for the disease are similar to those for stroke. OBJECTIVE: To determine what relationship, if any, exists between AMD and incident clinical stroke. DESIGN: Prospective cohort study. SETTING: The population-based Atherosclerosis Risk in Communities Study, which was conducted in Minnesota, Maryland, Mississippi, and North Carolina. PATIENTS: 10 405 persons between 49 and 73 years of age who had no history of stroke or coronary heart disease. MEASUREMENTS: Participants had retinal photographs taken between 1993 and 1995. A standardized protocol was used to evaluate the photographs for the presence of drusen and other signs of AMD. Incident stroke events were identified and validated by reviewing case records. RESULTS: There were 498 early-stage and 10 late-stage cases of AMD in the cohort (n = 508). Over a 10-year period, 241 persons had an incident stroke event. After adjusting for age, sex, ethnicity, and site, the authors found that persons with early-stage AMD had a higher cumulative incidence of stroke than those without the disease (4.08% vs. 2.14%). The presence of early-stage AMD was associated with a higher adjusted risk for stroke (hazard ratio, 1.87 [95% CI, 1.21 to 2.88]). Further adjustment for systolic blood pressure, diabetes, cigarette smoking, and use of antihypertensive medications did not substantially alter this association (hazard ratio, 1.85 [CI, 1.19 to 2.87]). The authors found that the association between early-stage AMD and stroke varied by study site and patient ethnicity. Multivariable-adjusted hazard ratios were 3.15 and 1.07 in samples of white patients in Minnesota and Maryland, respectively; 3.77 in a sample of African-American patients in Mississippi; and 0.33 in a sample of mostly white patients (91%) in North Carolina. No site included sufficient numbers of both African-American and white patients to determine whether ethnicity contributed to the observed differences by study site. LIMITATIONS: There were few cases of late-stage AMD, and the cohort assembly method prohibited full understanding of variation by ethnicity and site. CONCLUSION: Middle-aged persons with signs of early-stage AMD have a higher risk for stroke independent of traditional stroke risk factors.

Aged↗

PubMed2006

An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study.

BACKGROUND: There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models. METHODS: Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15,792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors. RESULTS: The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A(2), vitamin B(6), interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011). CONCLUSIONS: Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Retinal vascular caliber in persons with type 2 diabetes: the Wisconsin Epidemiological Study of Diabetic Retinopathy: XX.

PURPOSE: To describe retinal vascular caliber and correlates in people with type 2 diabetes. DESIGN: Population-based study. PARTICIPANTS: Thirteen hundred seventy persons diagnosed to have diabetes at or after 30 years of age in an 11-county area in south central Wisconsin from 1980 to 1982. METHODS: Retinal photographs of 7 standard fields were taken; light box grading was done to determine retinopathy severity. Computer-assisted grading was done from a digitized image of field 1 to determine the central retinal arteriolar equivalent (CRAE; arteriolar caliber) and central retinal venular equivalent (CRVE; venular caliber). MAIN OUTCOME MEASURES: Retinal arteriolar and venular calibers. RESULTS: In multivariable analyses in persons with panretinal photocoagulation excluded, while controlling for refractive error, CRAE was associated independently with age (per 10 years, beta = -2.0 microm), mean arterial blood pressure (BP) (per 10 mmHg, beta = -2.2 microm), smoking status (current vs. never smoked, beta = 5.6 microm), and intraocular pressure (IOP) (per 1 mmHg, beta = 0.2 microm). The CRVE was associated independently with age (per 10 years, beta = -2.5 microm), mean arterial BP (per 10 mmHg, beta = -2.1 microm), smoking status (current vs. never smoked, beta = 11.6 microm), pack-years smoked (per 10 pack-years, beta = 1.0 microm), body mass index (per kg/m2, beta = 0.3 mm), pulse rate (per 10 beats/minute, beta = 1.5 microm), retinopathy severity (per 1 level, beta = 1.05 microm), and IOP (per 10 mmHg, beta = -0.5 microm). Smaller CRAEs and CRVEs were found in eyes with panretinal photocoagulation treatment than in eyes without such treatment. CONCLUSIONS: In persons with type 2 diabetes, variations in retinal vascular caliber are related to various systemic and ocular factors. Understanding these relationships may provide further insights into early retinal vascular changes in diabetes.

Adult↗

PubMed2006

Apolipoprotein E polymorphisms predict low density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants.

Elevated levels of low density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease, and recent advancements have provided evidence that carotid artery intima-media thickness (IMT) is associated with increased occurrence of cardiovascular events. Apolipoprotein E (ApoE) has been widely studied in regard to its role in lipid transport and metabolism, but the role that ApoE genetic variation plays in relation to carotid artery IMT and risk of incident coronary heart disease remains a subject of debate. In 1987-2001, the authors examined the effect of each ApoE allele (epsilon2, epsilon3, epsilon4) on LDL cholesterol and carotid IMT, as well as the association with coronary heart disease risk, in 12,491 participants of the US Atherosclerosis Risk in Communities Study. ApoE epsilon2, epsilon3, and epsilon4 allele frequencies were determined, respectively, in Whites (0.08, 0.77, 0.15) and African Americans (0.11, 0.67, 0.22). These alleles did not predict incident coronary heart disease in either racial group. The ApoE epsilon2 allele was associated with lower LDL cholesterol and the epsilon4 allele with higher LDL cholesterol in both Whites and African Americans. The ApoE epsilon2 and epsilon4 alleles were associated with carotid IMT measures in both racial groups, but, after adjusting for lipid parameters, only the epsilon4 allele was associated with carotid IMT measures in African Americans.

Apolipoproteins E↗

PubMed2006

Confounding of the relation between homocysteine and peripheral arterial disease by lead, cadmium, and renal function.

Homocysteine levels are associated with peripheral arterial disease (PAD) in observational studies. Lead and cadmium are risk factors for PAD that affect thiol metabolism, and they may partly explain the association of homocysteine with PAD. To evaluate the roles of lead and cadmium exposure in confounding the association between homocysteine and PAD, the authors performed a cross-sectional study among 4,447 persons aged > or = 40 years who participated in the 1999-2002 National Health and Nutrition Examination Survey (NHANES). PAD was defined as an ankle-brachial blood pressure index less than 0.90 in at least one leg. After adjustment for sociodemographic variables, the odds ratio for PAD in the highest quintile of homocysteine compared with the lowest was 1.92 (p(trend) = 0.004). Adjusting for blood lead and cadmium levels reduced this odds ratio to 1.37 (p(trend) = 0.13), and further adjusting for estimated glomerular filtration rate and smoking reduced it to 0.89 (p(trend) = 0.87). Adjustment for other risk factors did not affect this association. In the general population, the association of homocysteine level with PAD can be completely explained by confounding due to smoking, increased blood lead and cadmium levels, and impaired renal function. The association of lead and cadmium with PAD risk deserves further investigation.

Adult↗

PubMed2006

Apolipoprotein E gene and early age-related maculopathy: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and early age-related maculopathy (ARM) in middle-aged persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants from the Atherosclerosis Risk in Communities Study (n = 10139; age range, 49-73 years). METHODS: Retinal photography was performed on 1 randomly selected eye, and grading for presence of ARM was carried out using a modification of the Wisconsin ARM Grading System. Early ARM was defined as the presence of either soft drusen alone, retinal pigment epithelial depigmentation alone, or a combination of soft drusen with increased retinal pigment and/or depigmentation. DNA extracted from blood samples of participants were analyzed for common allelic variants of the APOE gene (epsilon2, epsilon3, and epsilon4). MAIN OUTCOME MEASURES: Presence of early ARM on retinal photographs. RESULTS: The prevalence of early ARM was similar in participants with different APOE genotypes: epsilon2/epsilon2 (5.9%), epsilon2/epsilon3 (5.2%), epsilon2/epsilon4 (3.2%), epsilon3/epsilon3 (5.2%), epsilon3/epsilon4 (4.9%), and epsilon4/epsilon4 (4.1%). After controlling for age, gender, race, cigarette smoking, and other factors, early ARM was not associated with APOE genotypes, with an odds ratio (OR) of 1.35 (95% confidence interval [CI], 0.54-3.38) for epsilon2/epsilon2 genotype, an OR of 1.06 (95% CI, 0.80-1.40) for epsilon2/epsilon3 genotype, an OR of 0.63 (95% CI, 0.32-1.24) for epsilon2/epsilon4 genotype, an OR of 0.99 (95% CI, 0.80-1.24) for epsilon3/epsilon4 genotype, and an OR of 0.88 (95% CI, 0.47-1.63) for epsilon4/epsilon4 genotype, as compared with epsilon3/epsilon3 genotype (reference). No associations were found for specific early ARM signs or in analyses stratified by age, gender, race, or cigarette smoking status. CONCLUSIONS: These data provide no evidence of a strong association between the APOE gene and early ARM in middle-aged persons. This suggests that APOE is not likely a major determinant of the early stages of ARM in younger people. However, our study does not exclude the possibility of a weaker association or that APOE may influence only the development of late ARM in older populations, as reported in other studies.

Aged↗

PubMed2006

C-reactive protein is a marker for human immunodeficiency virus disease progression.

BACKGROUND: Limited data on acute-phase C-reactive protein (CRP) levels in human immunodeficiency virus (HIV) infection exist. METHODS: We obtained a single measurement of CRP from 513 HIV-infected men in the Multicenter AIDS Cohort Study to examine the association between CRP and immune suppression and progression to AIDS. We estimated changes in CRP during the course of HIV infection in 81 of these individuals using specimens collected from October 1, 1984, to December 31, 1996. RESULTS: The cross-sectional associations between log(10) CRP were correlated inversely with CD4 lymphocyte counts (r=-0.17; P<.001) and directly with log10 HIV RNA levels (r=0.20; P<.001). Levels of CRP of more than 2.3 mg/L were associated with a decreased time to the development of AIDS (relative time to AIDS, 0.36; P<.001) compared with individuals with CRP levels of 1.2 mg/L or less, which remained significant after adjustment for CD4 lymphocyte counts and HIV RNA and hemoglobin concentrations. Levels of CRP significantly increased over time with mean slopes of 8.5% (95% confidence interval, 4.9%-12.2%) and 4.5% (95% confidence interval CI, 2.1%-6.9%) per year for individuals with and without progression to AIDS, respectively. Individuals had a geometric mean CRP level of 2.5 mg/L in the 6-month interval before progression to AIDS, which was an increase from a nadir of 1.0 mg/L at 6.5 years before progression to AIDS. CONCLUSIONS: Levels of CRP were associated with HIV disease progression independent of CD4 lymphocyte counts and HIV RNA levels. In addition, regardless of progression to AIDS, HIV-infected individuals had a significant increase in CRP over time. This may have implications for cardiovascular disease among HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Diabetic retinopathy in a multi-ethnic cohort in the United States.

PURPOSE: To describe the prevalence and risk factors of diabetic retinopathy in a multi-ethnic US population of whites, blacks, hispanics, and chinese. DESIGN: Cross-sectional study of 778 individuals from ages 45 to 85 years with diabetes, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Retinal photographs were obtained with a 45 degrees nonmydriatic digital fundus camera. Presence and severity of diabetic retinopathy were graded at a central reading center on the basis of a modification of the Airlie House classification system. All participants underwent a standardized interview, examination, and laboratory investigations. RESULTS: In this population with diabetes, the prevalence of any retinopathy was 33.2% and macular edema 9.0%. The prevalence of any diabetic retinopathy and macular edema was significantly higher in blacks (36.7% and 11.1%) and hispanics (37.4% and 10.7%) than in whites (24.8% and 2.7%) and chinese (25.7% and 8.9%) (P = .01 and P = .007, comparing racial/ethnic differences for retinopathy and macular edema, respectively). Significant independent predictors of any retinopathy were longer duration of diabetes, higher fasting serum glucose, use of diabetic oral medication or insulin, and greater waist-hip ratio. Race was not an independent predictor of any retinopathy. CONCLUSIONS: This study provides contemporary data on the prevalence of and risk factors for diabetic retinopathy among whites, blacks, hispanics, and chinese participating in the MESA.

Aged↗

PubMed2006

Retinal vascular caliber, cardiovascular risk factors, and inflammation: the multi-ethnic study of atherosclerosis (MESA).

PURPOSE: To describe the relationship of retinal arteriolar and venular caliber with cardiovascular risk factors, including inflammatory biomarkers, in a multiethnic population of whites, blacks, Hispanics, and Chinese. METHODS: A cross-sectional study comprising 5979 persons aged 45 to 84 years residing in six U.S. communities. Retinal vascular caliber was measured and summarized from digital retinal photographs. Standard cardiovascular risk factors, including biomarkers of inflammation (e.g., high-sensitivity C-reactive protein [hsCRP], interleukin [IL]-6, and plasma fibrinogen) and endothelial dysfunction (e.g., soluble intercellular adhesion molecule [sICAM]-1 [, plasminogen activator inhibitor [PAI]-1) were assessed. RESULTS: Mean retinal arteriolar caliber was 144.1+/-14.4 (SD) microm, and venular caliber 214.0+/-22.2 microm. In models controlling for age, gender, race-ethnicity, and center, smaller retinal arteriolar caliber was related to higher systolic and diastolic blood pressure, hypertension status, current alcohol consumption, greater body mass index, and higher levels of total homocysteine; larger retinal arteriolar caliber was related to diabetes, current cigarette smoking, and higher levels of plasma fibrinogen; and larger retinal venular caliber was related to diabetes, current cigarette smoking, greater body mass index and waist-hip ratio, higher levels of serum glucose, plasma triglyceride, plasma LDL-cholesterol, hsCRP, plasma fibrinogen, IL6, sICAM-1, and PAI-1 and lower levels of HDL-cholesterol. In multivariate analyses, blacks and Hispanics had larger retinal arteriolar and venular calibers than did whites and Chinese. CONCLUSIONS: Retinal arteriolar and venular caliber is associated with a range of cardiovascular risk factors, including hypertension, diabetes, measures of obesity, and dyslipidemia. Venular caliber is also associated with systemic inflammation.

Arterioles↗