Carotid Intima-media Wall Thickness Research Articles

Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population.

Atherosclerosis can be viewed as a low grade inflammatory process, and genetic polymorphisms within cytokines are candidate risk factors for the development of atherosclerosis. We examined the association of a common functional variant in the IL-6 gene with carotid intimal-medial wall thickness (IMT) and the presence of plaques in a randomly selected, cross-sectional Australian population. B-mode carotid ultrasound was performed on 1109 subjects aged 27-77 years, who were genotyped for the IL-6 polymorphism (-174G>C) and assessed for conventional cardiovascular risk factors. The frequency of the IL-6 -174C allele was 0.41. Initial univariate analysis showed no association of the IL-6 -174G>C polymorphism with carotid IMT. Multivariate analysis however showed an association of the IL-6 -174C allele with increased IMT in subjects older than the median age of 53 years (P=0.005). Initial univariate analysis of the IL-6 -174G>C polymorphism and carotid plaque showed no association in the whole sample. In multivariate analysis the -174C allele was independently associated with an increased risk of carotid plaque in the whole sample (CC vs GG, OR=2.22, 95% CI=1.32 to 3.73, P=0.003). This study shows that the IL-6 -174G>C variant is independently associated with carotid plaque formation in the whole population and an increased carotid IMT in older subjects within a randomly selected, cross-sectional Australian population.

The relationship between carotid atherosclerosis and platelet aggregation in elderly

The aim of this study is to assess the relationship between the carotid wall intima media thickness (IMT) and atheroma plaques due to atherosclerosis and platelet aggregation among elderly. The first stage of the study was performed by analyzing platelet aggregation in a total of 28 elderly patients divided into two groups. The first group consisted of 14 cases with carotid atheroma plaque (Patient group I) and the second group of patients were without carotid atheroma plaque (Control group I). At the second stage of the study, the cases were regrouped according to the carotid IMT. Patients with IMT above 1 mm (Patient group II, n=10) and under 1 mm (Control group II, n=14) were compared regarding platelet aggregation. Platelet aggregation was induced in the platelet-rich plasma using 5 μM ADP, 0.2 mg/ml collagen and 1.2 mg/ml ristocetin. Between patients with and without atheroma, no difference was noted in terms of platelet aggregation. Between platelet aggregation results of patients with intimal thickness above and under 1 mm, no significant difference was also noted. Between elderly cases with or without atherosclerosis, there was no difference with respect to platelet aggregation. Platelet aggregation measurements cannot be used as a marker of atherosclerosis in elderly population.

Multi-Ethnic Study of Atherosclerosis: objectives and design.

The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.

Westernization of lifestyle markedly increases carotid intima-media wall thickness (IMT) in Japanese people

To illustrate the impact of westernization of lifestyle on the development of pre-clinical atherosclerosis in Japanese people, we compared risk factors for atherosclerosis such as serum lipids, blood pressure, BMI, insulin resistance, and smoking habits between non-diabetic native Japanese and non-diabetic Japanese Americans. Two hundred and twenty two non-diabetic Japanese Americans living in Hawaii and 271 non-diabetic Japanese living in Hiroshima, Japan were studied. Carotid intima-media wall thickness (IMT) was measured in all subjects by one physician. For all measurements the same ultrasound instrumentation was used. Although no significant differences were seen in serum total cholesterol (TC), triglycerides, or LDL-cholesterol (LDL-C) levels between the two groups in the 1998 study, previous to 1998 these three parameters were significantly higher in Japanese Americans than native Japanese in our study which has spanned the past 20 years. IMT was significantly greater in Japanese Americans than native Japanese (1.20±0.03 mm vs. 0.98±0.03 mm, (mean±S.E.) respectively; P<0.0001). Moreover Japanese Americans reach an IMT of 1.1 mm at age 50, whereas the native Japanese reach this value at age 70. These observations indicate more rapid atherosclerosis progression in Japanese Americans. Based on our IMT measurements, the status and the estimated progression of atherosclerosis in Japanese Americans is increased. Since IMT is a validated endpoint for assessment of atherosclerotic disease risk, it can be concluded that Japanese Americans are at increased risk for cardiovascular disease.

Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound.

Recent studies have suggested increased cardiovascular disease among patients with rheumatoid arthritis (RA). We undertook this study to obtain morphologic evidence of subclinical atherosclerosis in RA patients. We used high-resolution B-mode ultrasound to compare carotid artery intima-media wall thickness (IMT) between 53 postmenopausal women with RA and 53 controls matched by age, sex, and menopause status. No subject in either group had a history of atherosclerosis or its complications. We investigated the association between IMT and relevant clinical and therapeutic variables, including the impact of low-dose corticosteroid therapy (< or = 10 mg/day prednisolone). The mean +/- SD IMT of the left and right common carotid arteries in RA patients was significantly greater than that in controls (0.77 +/- 0.09 mm versus 0.68 +/- 0.14 mm; P < 0.001). Early RA (duration < or = 1 year) was associated with lesser IMT than was RA of longer duration (0.72 +/- 0.03 mm versus 0.78 +/- 0.01 mm; P < 0.04). Prednisolone use was not associated with increased IMT (0.78 +/- 0.02 mm in nonusers versus 0.76 +/- 0.01 mm in users; P = 0.38). Our data indicate that RA patients have an ultrasonic marker of early atherosclerosis consistent with an increased risk for atherosclerosis.

The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: the atherosclerosis risk in communities study

Purpose The aim of this report is to describe the prevalence of retinopathy and its associations with atherosclerosis and vascular risk factors in people with diabetes. Design Cross-sectional study. Participants Persons with diabetes, having gradable fundus photographs, from a biracial population-based cohort of adults (ages 51–72 years), and living in four United States communities (Forsyth County, North Carolina; the city of Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland) were studied from 1993 to 1995. Methods Lesions typical of diabetic retinopathy were detected by grading a 45° color fundus photograph of one eye of each participant, using a modification of the Airlie House classification system. Main outcome measure Severity of diabetic retinopathy (none, minimal nonproliferative, moderate nonproliferative, severe nonproliferative, and proliferative) and macular edema. Results Retinopathy was detected in 328/1600 (20.5%) of those with diabetes; 114/1724 (6.6%) had hard exudate, 28/1600 (1.8%) had proliferative diabetic retinopathy, and 27/1662 (1.6%) had macular edema. The prevalence of diabetic retinopathy was higher in blacks (27.7%) compared with whites (16.7%). Controlling for duration of diabetes, serum glucose, systolic blood pressure, and type of diabetes medications taken, severity of retinopathy was associated with carotid artery intima-media wall thickness (odds ratio [OR]/0.1-mm thickness 1.09; 95% confidence interval [CI], 1.01, 1.17; P = 0.01), serum albumin (OR/0.1 g/dl 0.94; 95% CI, 0.88, 0.99; P = 0.02), but not race (OR blacks versus whites,1.24; 95% CI, 0.88, 1.75; P = 0.21). Severity of diabetic retinopathy was not associated with coronary artery disease or stroke history or any of the plasma lipids studied. Controlling for age, gender, duration of diabetes, serum glucose, and type of diabetes medications taken, the presence of retinal hard exudates was associated with plasma low-density lipoprotein cholesterol (OR/10 mg/dl 1.18; 95% CI, 1.09, 1.29; P < 0.001), and plasma Lp(a) (OR/10 mg/dl 1.02; 95% CI, 1.00, 1.05; P = 0.04) but not race or blood pressure. Conclusions These data suggest that plasma lipids are associated with the presence of hard exudate and that carotid artery intima-media wall thickness is associated with retinopathy, but other manifestations of atherosclerosis and most of its risk factors are not associated with severity of diabetic retinopathy.

Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes

Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes. B-mode carotid ultrasound was performed among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.

Hyperhomocyst(e)inemia and Hemostatic Factors: The Atherosclerosis Risk in Communities Study

PURPOSE: To determine whether homocyst(e)ine (H(e)) is related to hemostatic factors in a population-based sample without evidence of cardiovascular disease. METHODS: A subsample of 660 participants—67 African-American women, 53 African-American men, 201 white women, and 339 white men—was selected from the Atherosclerosis Risk in Communities Study baseline cohort. This was based on carotid intimal-medial wall thickness above the 90th percentile or below the 75th percentile of the population distribution, assessed by B-mode ultrasonography. Unadjusted and multivariable-adjusted associations between fasting plasma H(e) and the hemostatic factors fibrinogen, factor VII:c, factor VIII:c, protein C antigen, hematocrit, platelet count, β-thromboglobulin (β-TG), tissue plasminogen activator (tPA), PAI-1, D-dimer, and lipoprotein[a] were examined. RESULTS: Mean age-adjusted H(e) was positively, albeit weakly, correlated with β-TG, tPA, hematocrit, D-dimer and PAI-1; inversely correlated with protein C; and was higher in smokers, men and African-Americans. In multivariable regression, β-TG, tPA, and factor VII:c were positively associated with H(e), as well as age, black race, male sex, and current cigarette smoking. CONCLUSIONS: These cross-sectional data for a biracial group of middle-aged individuals suggest that H(e) levels falling below values consistent with homocyst(e)inemia are associated with several prothrombotic factors after adjustment for sociodemographic factors. If H(e) change is antecedent to altered hemostasis, FDA-mandated fortification of grain products with folic acid for prevention of fetal neural tube defects may lead to both reduced plasma H(e) levels and improved hemostatic profiles.

Influence of the extent of westernization of lifestyle on the progression of preclinical atherosclerosis in Japanese subjects.

To clarify the influence of a westernized lifestyle on the risk factors for atherosclerosis and preclinical atherosclerosis in Japanese subjects, we surveyed a Japanese population and Japanese immigrants in the United States. Based on the extent of westernization of their lifestyle, the subjects were classified as Japanese (J), first generation Japanese-Americans (JA-I), and second or later generation Japanese-Americans (JA-II). The consumption of animal fat and simple carbohydrates increased in the order of J, JA-I, and JA-II, while the subjects with strenuous physical activity decreased in the same order. The waist-hip ratio, fasting insulin level, serum cholesterol and triglyceride levels, and prevalence of hypertension increased in the same order as the dietary changes. The carotid intima-media wall thickness and the plaque size, which are indices of preclinical atherosclerosis, also increased in the order of J, JA-I, and JA-II. These data indicate that a westernized lifestyle aggravates the risk factors for atherosclerosis and influences the progression of preclinical atherosclerosis, in correspondence with the extent of westernization.

Antioxidant vitamins and the risk of carotid atherosclerosis: The perth carotid ultrasound disease assessment study (CUDAS)

OBJECTIVESThis study examined whether dietary intake or plasma levels of antioxidant vitamins were independently associated with common carotid artery intima-media (wall) thickness (IMT) or focal plaque, or both, in a large, randomly selected community population.BACKGROUNDOxidation of low-density lipoprotein (LDL) cholesterol is thought to be important in early atherogenesis. Antioxidant micronutrients may therefore protect against lipid peroxidation and atherosclerotic vascular disease.METHODSWe studied 1,111 subjects (558 men and 553 women; age 52 ± 13 years [mean ± SD], range 27 to 77). We measured dietary vitamin intake and fasting plasma levels of vitamins A, C and E, lycopene and alpha- and beta-carotene and performed bilateral carotid artery B-mode ultrasound imaging.RESULTSAfter adjustment for age and conventional risk factors, there was a progressive decrease in mean IMT, with increasing quartiles of dietary vitamin E intake in men (p = 0.02) and a nonsignificant trend in women (p = 0.10). Dietary vitamin E levels accounted for 1% of the variance in measured IMT in men. For plasma antioxidant vitamins, there was an inverse association between carotid artery mean IMT and plasma lycopene in women (p = 0.047), but not in men. None of the other dietary or plasma antioxidant vitamins, nor antioxidant vitamin supplements, were associated with carotid artery IMT or focal carotid artery plaque.CONCLUSIONSThis study provides limited support for the hypothesis that increased dietary intake of vitamin E and increased plasma lycopene may decrease the risk of atherosclerosis. No benefit was demonstrated for supplemental antioxidant vitamin use.

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.

Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness

Aim: our study assessed whether minor or major hormonal deficiency influenced oxidative status and vascular wall structure in menopausal women. Methods: the study series was made up of 62 non hypertensive non diabetic menopausal women (mean age 52.3±4.7 years) divided into two groups depending on duration of menopause (group 1 duration 0–5 years; group 2 duration over 5 years). Total cholesterol (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), malondialdehyde (MDA) and common carotid artery wall intima-media thickness (IMT) were determined in the entire series. Results: mean TC, LDL-C, TG, MDA and IMT values were higher in group 2 than group 1. The intergroup difference between MDA ( P<0.007) and IMT values ( P<0.006) values was statistically significant. Conclusions: the study revealed a close temporal correlation between plasma oxidative stress and carotid wall IMT, jeopardizes vascular wall status as menopause proceeds.

Carotid plaque and intima-media thickness assessed by b-mode ultrasonography in subjects ranging from young adults to centenarians.

BACKGROUND AND PURPOSE-To investigate relationships among plaque formation, increasing intima-media thickness, and age, we examined ultrasonographically carotid arteries of subjects who had no major atherosclerotic risk factors and who ranged in age from young adults to centenarians. We studied 319 healthy subjects (154 men, 165 women; age range, 21 to 105 years) with no history of hypertension, diabetes mellitus, or atherosclerotic disease. Mean intima-media wall thickness (IMT) of common carotid arteries at plaque-free sites and prevalence of plaques were evaluated by B-mode ultrasound. Mean common carotid IMT increased in a linear manner with age for all decades of life, including centenarians [IMT=(0.009xAge)+0.116] (r=0.83). In centenarians (n=30), intima-media complexes were diffusely thickened (mean IMT, 1.01 mm). Plaque prevalence increased up to the tenth decade of life (83.3%, n=30) but decreased in centenarians (60.0%). IMT and plaque prevalence were closely associated in the seventh and eighth decades of life but not at older ages. The present study indicates that increased IMT is a physiological effect of aging that corresponds to diffuse intimal thickening, especially in very elderly persons, and that IMT is distinct from pathological plaque formation.

Homocysteine Predicts Incident Isolated Systolic Hypertension in Older Adults

0019 Untreated isolated systolic hypertension (ISH) indicates arterial stiffening and carries a risk for both stroke and cardiovascular disease. Elevated plasma homocysteine, a metabolite of the essential amino acid methionine, has been linked to vascular stiffness. 187 normotensive (defined as systolic blood pressure (SBP) &lt; 160 mmHg and diastolic blood pressure &lt; 90 mmHg) men and women (mean age 71.29 + 6.3 yrs) were followed for an average of 7 years for incident ISH. ISH was defined as a SBP ≥160 mmHg (while maintaining a DBP of &lt; 90 mmHg) at least one time at 3 year follow-up visits, or the initiation of antihypertensive therapy. The mean baseline systolic and diastolic blood pressures (DBP) were 127 and 69 mmHg, respectively. Over the 7 year period, 59(31.5%) participants developed ISH, 76% qualified by antihypertensive use, and 24% by blood pressure values. The Kaplan Meier Estimate of 7 year survival free from ISH was 67% (95% CI: 61%, 74%). The relationship between incident ISH and the traditional cardiovascular risk factors, creatinine, homocysteine, and carotid artery intima-media wall thickness (IMT) was assessed by Cox proportional hazards regression. The strongest predictor of incident ISH was baseline SBP. For participants with baseline SBPs of &lt; 130, 130-139, and 140+ mmHg, the corresponding 7 year survival free from ISH was 80% (95% CI: 73%, 88% ), 53% (95%CI: 38%, 67%), and 44% (95% CI: 26%, 62%). Factors independently associated with time to ISH were higher triglycerides (upper tertile,RR=2.0, p=0.012), homocysteine levels (&gt; 12.0 μmol/l, RR=2.2, p=0.005), and baseline SBP (per 10 mmHg,RR=1.4, p=0.003). The results were similar when the analysis was restricted to the 157 participants with a baseline SBP of &lt; 140 mmHg. Baseline IMT was found to be univariately related to time to ISH (RR per each 1.0 mm increment=3.0; p=0.016). In multivariate analysis, this association remained independent of triglycerides and homocysteine, but not baseline SBP (RR per each 1.0 mm increment=2.5; p=0.049). In conclusion, among normotensive older adults, 32% can be expected to develop ISH over a 7 year period, and higher triglyceride and homocysteine levels are risk factors.

Cardiovascular Risk In Women With Polycystic Ovary Syndrome

Compared with normal cycling women of similar age, women with polycystic ovary syndrome (PCOS) have an adverse lipid profile and an increased prevalence of Type II diabetes and hypertension. These woman also appear to have greater subclinical atherosclerotic disease, as demonstrated by greater carotid intimamedia wall thickness and higher levels of coronary calcification. Given the high prevalence of PCOS in the female population, this condition may potentially account for a significant proportion of the atherosclerotic heart disease observed in younger women. This article reviews the issues and uncertainties surrounding the PCOS-CHD association.

Insulin resistance and five-year progression of carotid intimal-medial wall thickness:

0026 Insulin resistance (IR) is thought to be an important risk factor for atherosclerosis. It is unclear, however, whether the effect is independent of other cardiovascular (CV) risk factors that cluster with IR, e.g., obesity, hypertension (HTN), and hyperlipidemia. IRAS is a multi-ethnic epidemiologic cohort study investigating the association between IR and CV disease. IR was measured by the frequently sampled intravenous glucose tolerance test with minimal model analysis in 773 non-diabetic persons aged 60 years (range 44 - 75) who participated in the baseline IRAS examination (1992-4). Intimal-medial thickness (IMT) of the carotid arteries was measured by B-mode ultrasonography as an index of atherosclerosis at baseline and at the 5-year follow-up exam (1998-9). Both scans were read at the follow-up time point to eliminate possible reader drift. We modeled change in IMT on IR, adjusting for baseline IMT using a general linear models approach. The models adjusted progressively for demographic variables and CV risk factors. Overall, common carotid (CCA) IMT increased 30 μm (s.e. = 8 μm). Average IR at baseline was 2.2 units (range 0 - 14.2). Adjusting for age, sex, ethnicity, clinic and baseline measurement, CCA IMT increased 20 μm (p=0.007) for a 2 unit increase in IR (change from 25th to 75th percentile). Further adjustment for baseline HDL, LDL, smoking, HTN and glycemia attenuated the effect (17 μm, p=0.05). Adjustment for BMI and waist-hip ratio explained some of the effect (13 μm, p=0.13). No significant association was observed between IR and progression in the internal carotid artery. Analyses incorporating hierarchical measurement error models for IMT were performed to confirm these results. As expected in these analyses, the IR effect was somewhat attenuated, but not eliminated. In summary, IR is associated with progression of carotid atherosclerosis, but this effect may be mediated through the associated cluster of CV risk factors.

Cardiovascular risk factors and cognitive decline in middle-aged adults.

To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale-Revised and the first-letter word fluency (WF) test using letters F, A, and S. In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima-media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Apolipoprotein E and carotid artery atherosclerosis: the Rotterdam study.

Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery atherosclerosis. A population-based cross-sectional study was performed on 5401 subjects. Atherosclerosis was noninvasively assessed by the common carotid artery intima-media wall thickness and the presence of plaques in the carotid arteries. The relationship of the 6 APOE genotypes with these 2 indicators was studied with linear and logistic regression analysis, respectively, with adjustments for age and sex. Carriers of the E2E3 genotype had a thinner intima-media wall thickness (mean difference, -0.02 mm; 95% CI, -0.03 to -0.01 mm) and fewer plaques (odds ratio for >3 plaques at 6 sites, 0.6; 95% CI, 0.4 to 0.8) than the most common group, E3E3. The E4E4 group had slightly more atherosclerosis, but this was not statistically significant. Adjusting for the level of the apolipoprotein E protein (apoE) in serum or total or HDL cholesterol did not essentially change these findings. Our results suggest that APOE*4 is not an important risk factor for carotid artery atherosclerosis. The inverse relationship of E2E3 with carotid artery atherosclerosis seems to be independent of serum apoE and total and HDL cholesterol levels. However, the low frequency, together with the small effects, implies that any protective effect of E2E3 on carotid artery atherosclerosis is limited.

Serum ferritin and C282Y mutation of the hemochromatosis gene as predictors of asymptomatic carotid atherosclerosis in a community population.

Serum ferritin and heterozygosity for the C282Y mutation of the hemochromatosis gene have both been associated with an increased risk of cardiovascular events. The purpose of the study was to test whether either is a risk predictor for asymptomatic carotid atherosclerosis. We assessed carotid intima-media wall thickness (IMT) and focal plaque formation by high-resolution B-mode ultrasound, conventional risk factors, serum ferritin levels, and the C282Y mutation of the hemochromatosis gene in a randomly selected community population of 1098 subjects (545 women and 553 men) aged 27 to 77 years. After adjustment for conventional risk factors, serum ferritin was not associated with carotid mean IMT. Women with ferritin values over the first quartile (>34 microg/L) had an adjusted odds ratio of 2.1 (95% CI, 1. 3 to 3.4; P:=0.0016) for carotid plaque compared with the first quartile. Ferritin was not associated with carotid plaque in men. Subjects who were heterozygous for the C282Y mutation constituted 11. 4% of the population, and there was no independent association of this genotype with either carotid IMT or focal plaque formation. We conclude that in our community population, C282Y genotype status was not a risk predictor for either carotid mean IMT or plaque formation. Serum ferritin values in women were independently associated with carotid plaque.

Influence of leisure time physical activity and television watching on atherosclerosis risk factors in the NHLBI Family Heart Study

Physical activity favorably influences atherosclerosis risk factors but only a few studies in adults considered the time watching television (TV) as a measure of physical inactivity. We therefore determined in a population-based sample of 1778 subjects from the NHLBI Family Heart Study (FHS) whether leisure time physical activity and TV watching have independent or interactive associations with cardiovascular disease risk factors and carotid artery intima-media wall thickness (IMT). Subjects were free from diabetes mellitus and clinically-ascertained coronary artery disease and did not take lipid-lowering or antihypertensive drugs. Only 0.7 and 1.3% of the variance in leisure time physical activity in women and men, respectively, was explained by the amount of TV watching. Leisure time physical activity had a clearly favorable, and TV watching an unfavorable association with anthropometric measurements (BMI (body mass index), waist girth, waist-hip ratio, subscapular and triceps skinfold thickness). The odds ratio (95% CI) of being overweight was 0.41 (0.28–0.62) in women and 0.69 (0.46–1.04) in men in the highest quartile of leisure time physical activity compared to the lowest quartile. The odds ratio increased for increasing quartiles of TV watching to 2.12 (1.45–3.10) in women and 1.61 (1.07–2.43) in men. Watching TV only 1 h per day in women with a BMI of 30 kg/m 2 and doing about 75 min of moderate exercise per week was associated with a BMI 1.8 kg/m 2 lower than in women watching TV 3 h per day and doing the same amount of exercise. Those with twice the amount of moderate exercise and watching TV 1 h per day had a BMI 0.45 kg/m 2 lower. Furthermore, leisure time physical activity was negatively associated with concentrations of triglycerides and positively with HDL cholesterol in both genders. TV watching was significantly positively associated with triglycerides and slightly negatively with HDL cholesterol in men. The observed associations of leisure time physical activity and TV watching with atherosclerosis risk factors were independent from each other. Finally, we analyzed the relation between leisure time physical activity, TV watching and the degree of IMT of the carotid arteries. Neither of these two measures was significantly associated with IMT. In summary, TV watching, in addition to leisure time physical activity, shows an independent association with obesity-related anthropometric measurements, HDL and triglycerides. Decreasing the amount of TV watching might be effective as a first step in reducing atherosclerosis risk factors, especially overweight.