Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital and the Medical School at the University of Tampere, 33014 Tampere, Finland. firstname.lastname@example.org
Individuals suffering from ATH (adult-type hypolactasia), defined by the LCT (gene encoding lactase-phlorizin hydrolase) C/C(-13910) genotype (rs4988235), use less milk and dairy products and may have higher plasma HDL (high-density lipoprotein) and lower triacylglycerol (triglyceride) concentrations than their counterparts without ATH. To investigate the effects of ATH status on the early markers of atherosclerosis, we examined its association with CIMT (carotid intima-media thickness), CAC (carotid artery compliance) and brachial artery FMD (flow-mediated dilation) in a young population-based cohort of otherwise healthy individuals. As part of the Cardiovascular Risk in Young Finns Study, we performed CIMT, CAC and FMD analyses, LCT C/T(-13910) genotyping and risk factor determination in 2109 young subjects 24-39 years of age (45% males) at the time of the examination. The consumption of both milk and dairy products was lowest and the consumption of alcohol highest in subjects with the C/C(-13910) genotype (P
Atherosclerosis begins early in life and is the major underlying cause of cardiovascular morbidity and death. Yet, population-based information on age and sex differences in the extent and morphology of atherosclerosis throughout life is scarce. Carotid atherosclerosis can be visualized with B-mode ultrasound and is a marker of atherosclerosis elsewhere in the circulation. We assessed both the prevalence and the morphology of carotid atherosclerosis by B-mode ultrasound in 3016 men and 3404 women, 25 to 84 years old, who participated in a population health survey. The participation rate was 88%. Plaque morphology was graded according to whether a plaque was predominantly soft (echolucent) or hard (echogenic). Atherosclerotic plaques were found in 55.4% of the men and 45.8% of the women. In men, there was a linear increase with age in the prevalence of carotid atherosclerosis, whereas in women, there was a curvilinear age trend, with an inflection in the prevalence rate of women at approximately 50 years of age. The male predominance in atherosclerosis declined after the age of 50 years, the plaque prevalence being similar in elderly men and women. Men had softer plaques than women; this sex difference in plaque morphology increased significantly (P=0.005) with age. The sex difference in the prevalence of atherosclerosis and the female age trend in atherosclerosis show significant changes at the age of approximately 50 years, suggesting an adverse effect of menopause on atherosclerosis. The higher proportion of soft plaques in men compared with women increases with age and may partly account for the prevailing male excess risk of coronary heart disease in the elderly despite a similar prevalence of atherosclerosis in elderly men and women.
The authors analyse herein the reasonable use of ultrasonographic methods of examination of carotid arteries for diagnosis of stenosing pathology in hypertensive patients. At the stage of primary medical care of the city of Chelyabinsk, a non-selective referral of patients presenting with elevated arterial pressure to duplex ultrasonography of the carotid artery is not uncommon. Doubtful criteria of selecting the hypertensive patients who really require undergoing ultrasonography of the carotid artery result in low efficacy of the examination.
Apolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).
B-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p=0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p=0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p=0.008), triglycerides (p=0.006), remnant lipoprotein-cholesterol (RLP-C) (p=0.023), and lipoprotein(a) [(Lp(a)] (p=0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p=0.041).
ApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.
Exposure to cardiovascular risk factors during childhood and adolescence may be associated with the development of atherosclerosis later in life.
To study the relationship between cardiovascular risk factors measured in childhood and adolescence and common carotid artery intima-media thickness (IMT), a marker of preclinical atherosclerosis, measured in adulthood.
Population-based, prospective cohort study conducted at 5 centers in Finland among 2229 white adults aged 24 to 39 years who were examined in childhood and adolescence at ages 3 to 18 years in 1980 and reexamined 21 years later, between September 2001 and January 2002.
Association between cardiovascular risk variables (levels of low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides; LDL-C/HDL-C ratio; systolic and diastolic blood pressure; body mass index; smoking) measured in childhood and adulthood and common carotid artery IMT measured in adulthood.
In multivariable models adjusted for age and sex, IMT in adulthood was significantly associated with childhood LDL-C levels (P =.001), systolic blood pressure (P
Comment In: JAMA. 2003 Nov 5;290(17):2320-214600192
BACKGROUND AND PURPOSE: Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). METHODS: IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. RESULTS: During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex. CONCLUSIONS: In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.
Carotid plaque and intima-media thickness (IMT) are recognized as risk factors for ischemic stroke, but their predictive value has been debated and varies between studies. The purpose of this longitudinal population-based study was to assess the risk of ischemic stroke associated with plaque area and IMT in the carotid artery.
IMT and total plaque area in the right carotid artery were measured with ultrasound in 3240 men and 3344 women aged 25 to 84 years who participated in a population health study in 1994 to 1995. First-ever ischemic strokes were identified through linkage to hospital and national diagnosis registries, with follow-up until December 31, 2005.
Incident ischemic strokes occurred in 7.3% (n=235) of men and 4.8% (n=162) of women. The hazard ratio for 1 SD increase in square-root-transformed plaque area was 1.23 (95% CI, 1.09-1.38; P=0.0009) in men and 1.19 (95% CI, 1.01-1.41; P=0.04) in women when adjusted for other cardiovascular risk factors. The multivariable-adjusted hazard ratio in the highest quartile of plaque area versus no plaque was 1.73 (95% CI, 1.19-2.52; P=0.004) in men and 1.62 (95% CI, 1.04-2.53; P=0.03) in women. The multivariable-adjusted hazard ratio for 1 SD increase in IMT was 1.08 (95% CI, 0.95-1.22; P=0.2) in men and 1.24 (95% CI, 1.05-1.48; P=0.01) in women. There were no differences in stroke risk across quartiles of IMT in multivariable analysis.
In the present study, total plaque area appears to be a stronger predictor than IMT for first-ever ischemic stroke.
OBJECTIVE: Circulating oxidized LDL (Ox-LDL) is associated with clinical manifestations of atherosclerosis. However, no previous study has examined the relationship between subclinical atherosclerosis and Ox-LDL. The aims of the present study were to investigate the relationship between clinically silent ultrasound-assessed atherosclerotic changes in the carotid and femoral arteries and Ox-LDL and to explore the relationship between Ox-LDL, C-reactive protein, and the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. METHODS AND RESULTS: The study group (n=391) consisted of clinically healthy, 58-year-old men recruited from the general population. Ox-LDL was measured by using a specific monoclonal antibody, mAb-4E6. The results showed that Ox-LDL was related to intima-media thickness and plaque occurrence in the carotid and femoral arteries. In addition, Ox-LDL was associated with tumor necrosis factor-alpha and C-reactive protein. Circulating Ox-LDL was also associated with LDL cholesterol but not with blood pressure or smoking. When adjusting for other risk factors, both LDL cholesterol and Ox-LDL seemed to be independent predictors of plaque occurrence in the carotid and femoral arteries (odds ratios for quintile 5 versus quintile 1 were 2.17, P=0.049 and 2.25, P=0.050, for LDL cholesterol and Ox-LDL, respectively). CONCLUSIONS: Ox-LDL was associated with both subclinical atherosclerosis and inflammatory variables, supporting the concept that oxidatively modified LDL may play a major role in atherosclerosis development, although no causality can be shown in this cross-sectional study.
The role of the inflammatory mediator C-reactive protein (CRP) in atherosclerosis is recognized although its specific functions are not entirely clear. CRP binds to the Fcgamma receptor2A (FcgammaR2A) and its polymorphism, FCGR2A (Arg131His), strongly influences the binding. We wanted to evaluate the CRP-mediated proatherogenic process on early atherosclerosis and investigated whether CRP and FCGR2A show an interactive effect on carotid intima-media thickness (IMT). Polymorphisms of FCGR2A (Arg131His) and CRP (-717A > G, -286C > T > A, +1059G > C, +1444C > T and +1846G > A) were genotyped and their effects on IMT were analyzed in 2260 young adults participating in the Cardiovascular Risk in Young Finns Study. CRP haplotypes were constructed based on the CRP polymorphisms. The FCGR2A(Arg131His) polymorphism did not have an independent effect on IMT but a significant gene-gene interaction, epistasis, between FCGR2A and CRP genetics on IMT was found. The epistatic effect was seen in men at haplotype and genotypic level; both CRP haplotype GCGCG (-717, -286, +1059, +1444 and +1846) and CRP-717A > G polymorphism interacted with FCGR2A(Arg131His) on IMT. After adjustment with classical risk factors the P-values for interaction were P = 0.013 and P = 0.010, respectively. No associations were observed in women. In conclusion, this study showed that the effect of CRP genetics on early atherosclerotic changes is modulated by the FCGR2A genetics.
Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P