MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome.

Meckel syndrome (MKS) is a severe fetal developmental disorder reported in most populations. The clinical hallmarks are occipital meningoencephalocele, cystic kidney dysplasia, fibrotic changes of the liver and polydactyly. Here we report the identification of a gene, MKS1, mutated in MKS families linked to 17q. Mks1 expression in mouse embryos, as determined by in situ hybridization, agrees well with the tissue phenotype of MKS. Comparative genomics and proteomics data implicate MKS1 in ciliary functions.

Mutant CHUK and severe fetal encasement malformation.

We report an autosomal recessive lethal syndrome characterized by multiple fetal malformations, the most obvious anomalies being the defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. We identified the molecular defect that causes this syndrome, using a combined strategy of gene-expression arrays, candidate-gene analysis, clinical studies, and genealogic investigations. A point mutation in two affected fetuses led to the loss of the conserved helix­loop­helix ubiquitous kinase (CHUK), also known as IκB kinase α. CHUK has an essential role in the development of skin epidermis and its derivatives, along with various other morphogenetic events. (Funded by the Academy of Finland and others.).

A balanced translocation truncates Neurotrimin in a family with intracranial and thoracic aortic aneurysm.

BACKGROUND: Balanced chromosomal rearrangements occasionally have strong phenotypic effects, which may be useful in understanding pathobiology. However, conventional strategies for characterising breakpoints are laborious and inaccurate. We present here a proband with a thoracic aortic aneurysm (TAA) and a balanced translocation t(10;11) (q23.2;q24.2). Our purpose was to sequence the chromosomal breaks in this family to reveal a novel candidate gene for aneurysm. METHODS AND RESULTS: Intracranial aneurysm (IA) and TAAs appear to run in the family in an autosomal dominant manner: After exploring the family history, we observed that the proband's two siblings both died from cerebral haemorrhage, and the proband's parent and parent's sibling died from aortic rupture. After application of a genome-wide paired-end DNA sequencing method for breakpoint mapping, we demonstrate that this translocation breaks intron 1 of a splicing isoform of Neurotrimin at 11q25 in a previously implicated candidate region for IAs and AAs (OMIM 612161). CONCLUSIONS: Our results demonstrate the feasibility of genome-wide paired-end sequencing for the characterisation of balanced rearrangements and identification of candidate genes in patients with potentially disease-associated chromosome rearrangements. The family samples were gathered as a part of our recently launched National Registry of Reciprocal Balanced Translocations and Inversions in Finland (n=2575), and we believe that such a registry will be a powerful resource for the localisation of chromosomal aberrations, which can bring insight into the aetiology of related phenotypes.

Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle.

Meckel syndrome (MKS) is a lethal malformation disorder characterized classically by encephalocele, polycystic kidneys, and polydactyly. MKS is also one of the major contributors to syndromic neural tube defects (NTDs). Recent findings have shown primary cilia dysfunction in the molecular background of MKS, indicating that cilia are critical for early human development. However, even though four genes behind MKS have been identified to date, they elucidate only a minor proportion of the MKS cases. In this study, instead of traditional linkage analysis, we selected 10 nonrelated affected fetuses and looked for the homozygous regions shared by them. Based on this strategy, we identified the sixth locus and the fifth gene, CC2D2A (MKS6), behind MKS. The biological function of CC2D2A is uncharacterized, but the corresponding polypeptide is predicted to be involved in ciliary functions and it has a calcium binding domain (C2). Immunofluorescence staining of patient's fibroblast cells demonstrates that the cells lack cilia, providing evidence for the critical role of CC2D2A in cilia formation. Our finding is very significant not only to understand the molecular background of MKS, but also to obtain additional information about the function of the cilia, which can help to understand their significance in normal development and also in other ciliopathies, which are an increasing group of disorders with overlapping phenotypes.

Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?

Meckel syndrome (MKS) is a lethal malformation syndrome that belongs to the group of disorders that are associated with primary cilia dysfunction. Total of five genes are known to be involved in the molecular background of MKS. Here we have systematically analyzed all these genes in a total of 29 MKS families. Seven of the families were Finnish and the rest originated from elsewhere in Europe. We found 12 novel mutations in 13 families. Mutations in the MKS genes are also found in other syndromes and it seems reasonable to assume that there is a correlation between the syndromes and the mutations. To obtain some supportive information, we collected all the previously published mutations in the genes to see whether the different syndromes are dictated by the nature of the mutations. Based on this study, mutations play a role in the clinical phenotype, given that the same allelic combination of mutations has never been reported in two clinically distinct syndromes.

Hydrolethalus syndrome: neuropathology of 21 cases confirmed by HYLS1 gene mutation analysis.

Hydrolethalus syndrome is a lethal malformation syndrome with a severe brain malformation, most often hydrocephaly and absent midline structures. Other frequent findings are micrognathia, polydactyly, and defective lobation of the lungs. Hydrolethalus syndrome is inherited in an autosomal recessive manner and is caused by a missense mutation in the HYLS1 gene. Here, we report the neuropathologic features of 21 genetically confirmed cases. Typically, 2 separated cerebral hemispheres could be identified, but they lacked midline and olfactory structures and were situated basally with a massive accumulation of cerebrospinal fluid. Temporal and occipital lobes were hypoplastic, and normally developed hippocampi were not found. Primitive thalami and basal ganglia were fused in the midline. A hypothalamic hamartoma was a frequent finding, and brainstem and cerebellum were hypoplastic. Three cases were hydranencephalic, and 1 was anencephalic. A midline "keyhole" defect in the skull base was a constant finding. Histologically, the cortex was dysplastic. This pattern of brain pathology, clearly belonging to the midline patterning defects, seems to be unique for the hydrolethalus syndrome and combines features of disturbed neurulation, prosencephalization, and migration. Despite variation in the clinicopathologic phenotype, all cases in the series carried the same homozygous missense mutation in HYLS1.

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease.

BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein.

OBJECTIVE: Ageing, plasma circulating C-reactive protein (CRP), oxidized low-density lipoprotein (OxLDL) and homocysteine (Hcy) are associated with atherosclerosis. The aim of this study was to evaluate the relationship between age, inflammatory and oxidative stress-related markers with functional and structural changes of the arteries in asymptomatic persons. METHODS: CRP, OxLDL and Hcy were measured in 175 clinically healthy subjects, aged 40-70 years. Ultrasonography and pulse wave analysis were used to measure carotid intima-media thickness (IMT) and augmentation index (AIx). RESULTS: OxLDL was correlated with IMT (r = 0.24, P = 0.003), whereas CRP was correlated with AIx (r = 0.21, P = 0.005). No correlation was detected between Hcy and AIx or age-adjusted IMT. There was a significant association between AIx and age 50 years (r = 0.40; P = 0.001). In stepwise regression analysis age, weight, white blood cell count, OxLDL, heart rate and timing of the reflected waveform adjusted for height were significantly and independently associated with IMT (R = 0.41; P < 0.001). At the same time, AIx as the dependent variable correlated positively with age, gender, CRP and mean arterial pressure, and negatively with heart rate, weight and height, in stepwise regression analysis (R = 0.63; P < 0.001). CONCLUSION: The results of the present study showed that CRP, OxLDL, Hcy and age are not similarly related to AIx and IMT in asymptomatic persons. The results suggest that CRP and younger age are related to arterial stiffness, whereas OxLDL and older age become more important determinants of structural changes of the arteries in asymptomatic persons.

Decreased high-density lipoprotein (HDL) particle size, prebeta-, and large HDL subspecies concentration in Finnish low-HDL families: relationship with intima-media thickness.

OBJECTIVE: High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD. METHODS AND RESULTS: Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL < or =10th Finnish age-sex specific percentile) compared with unaffected family members and control subjects (9.1+/-0.04 nm versus 9.5+/-0.05 nm, P<0.0001, versus 9.8+/-0.03 nm, P<0.0001 [mean+/-SE]). Large HDL2b particles as well as prebeta-HDL concentration were significantly decreased among the affected family members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85+/-0.01 mm versus 0.79+/-0.01 mm; P<0.0001). Age, HDL2b, systolic blood pressure, and prebeta-HDL were significant independent determinants of mean IMT. CONCLUSIONS: The decreased levels of HDL2b and prebeta-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL2b and decreased prebeta-HDL levels correlate with increased IMT.

Association of carotid intima-media thickness with angiographic severity and extent of coronary artery disease.

The present study examined the association between carotid intima-media thickness (IMT) and severity and extent of coronary artery disease (CAD). B-mode ultrasound and quantitative coronary angiography were used to assess carotid and coronary artery atherosclerosis in 108 patients with known or suspected CAD who had been referred for cardiac catheterization. Maximum and mean IMT values of carotid arteries were measured and expressed as mean aggregate values. To evaluate anatomic severity and extent of CAD, several quantitative coronary angiographically derived parameters were incorporated into indexes. These quantitative coronary angiographic measurements reflected CAD severity, extent, and overall "atheroma burden" and were calculated for the entire coronary tree and separately for different coronary segments (i.e., left main, proximal, mid, and distal segments). Maximum and mean IMT values were significantly correlated with CAD severity (p = 0.004 and 0.005, respectively), extent (p = 0.022 and 0.016, respectively), and atheroma burden (p = 0.008 for the 2 values). Further, carotid IMT was correlated with quantitative angiographic indexes for mid and distal segments but not with the proximal segments of coronary vessels. In conclusion, our study shows an association between carotid IMT and severity and extent of CAD as assessed by quantitative coronary angiography. Carotid IMT seems to be a weaker predictor of coronary atherosclerosis in the proximal parts of the coronary tree than in the mid and distal parts.

Serum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease.

OBJECTIVE: The association between serum antibody levels to major periodontal pathogens and coronary heart disease (CHD) was analyzed in a prospective population-based study. METHODS AND RESULTS: The population comprised 1023 men (aged 46 to 64 years) in the Kuopio Ischemic Heart Disease Study. The subjects with CHD at baseline (n=113) were more often seropositive for Porphyromonas gingivalis IgA (38.9% versus 28.5%, P=0.021) and IgG (60.2% versus 46.7%, P=0.007) than those without CHD. During the 10-year follow-up, 109 men free from CHD at baseline experienced an acute myocardial infarction or CHD death. The men with an end point were more often seropositive for Actinobacillus actinomycetemcomitans IgA (15.5% versus 10.2%, P=0.019) than those who remained healthy. In the highest tertile of A. actinomycetemcomitans IgA-antibodies compared with the lowest one, the relative risk (RR) for an end point adjusted for CHD risk factors was 2.0 (95% confidence interval [CI], 1.2 to 3.3). In the Porphyromonas gingivalis IgA-antibody tertiles, the highest RR of 2.1 (1.3 to 3.4) was observed in the second tertile. All antibody levels correlated positively with the carotid artery intima-media thickness. CONCLUSIONS: High-serum antibody levels to major periodontal pathogens are associated with subclinical, prevalent, and future incidence of CHD. Periodontal pathogens or host response against them may contribute to the pathogenesis of CHD.

Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study.

BACKGROUND: Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). METHODS AND RESULTS: The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. CONCLUSIONS: These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

The effects of coffee consumption on lipid peroxidation and plasma total homocysteine concentrations: a clinical trial.

Despite extensive research, the cardiovascular effects of coffee consumption in humans remain controversial. Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine (tHcy) concentration in humans. The study consisted of a multiple-dose clinical supplementation trial and a single-dose study. In the long-term trial, 43 healthy nonsmoking men optionally consumed daily either no coffee, 3 cups (450 mL), or 6 cups (900 mL) of filtered coffee for 3 weeks, while in the short-term study 35 subjects consumed a single dose of 0, 1 (150 mL), or 2 cups (300 mL) of coffee. Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid. The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5% of the amount ingested daily. Plasma tHcy concentrations increased nonsignificantly, but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes. In conclusion, the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men. The effect of coffee consumption on tHcy concentrations needs further investigation.

Circulating oxidized low-density lipoprotein and its association with carotid intima-media thickness in asymptomatic members of familial combined hyperlipidemia families.

OBJECTIVE: Oxidized low-density lipoprotein (Ox-LDL)is implicated in the pathogenesis of atherosclerosis. Circulating oxidation-specific epitopes on plasma Ox-LDL has been linked with coronary artery disease, but its determinants and its association with early development of atherosclerosis in familial combined hyperlipidemia (FCHL) has not been very well studied. This study aimed to investigate the determinants of the circulating Ox-LDL and the association between Ox-LDL and carotid intima-media thickness (IMT) in asymptomatic members of FCHL families. METHODS AND RESULTS: Ox-LDL, susceptibility of LDL to oxidation in vitro, plasma 8-isoprostane and antioxidants, lipids and lipoproteins, LDL particle size, and carotid IMT were measured in 150 asymptomatic FCHL family members. Affected FCHL family members had reduced LDL particle size and lag time for LDL oxidation, increased plasma levels of Ox-LDL, increased plasma urate and alpha-tocopherol, and a trend for the increase of 8-isoprostane as compared with nonaffected FCHL. Ox-LDL was independently associated with serum LDL cholesterol, apoB, and 8-isoprostane in multivariate analysis but only univariately correlated with LDL particle size and lag time for LDL oxidation. In addition, Ox-LDL was significantly associated with carotid mean IMT independently of other clinical and biochemical variables in a multivariate model. CONCLUSIONS: Serum LDL cholesterol, apoB levels, and 8-isoprostane were the most important determinants of Ox-LDL. Ox-LDL is independently associated with carotid IMT in asymptomatic FCHL family members and can be used as a marker of early atherosclerosis in FCHL.

Polyphenol-rich phloem enhances the resistance of total serum lipids to oxidation in men.

In humans, polyphenol supplementation studies have resulted in inconsistent findings in lipid peroxidation. Our aim was to investigate the effects of a 4-week consumption of polyphenol-rich phloem on serum lipids and lipid peroxidation in the hydrophilic fraction of serum and on isolated lipoproteins. We conducted a randomized double-blind supplementation study consisting of 75 nonsmoking hypercholesterolemic men. Participants consumed 70 g daily of either rye bread (placebo) or phloem-fortified rye bread containing 31 mg (low polyphenol, LP) or 62 mg (high polyphenol, HP) of catechins. The ex vivo susceptibility of total serum lipids and VLDL and LDL to oxidation after copper induction was measured as a lag time to the maximal oxidation rate at the baseline and after the supplementation. In the HP group, an increase in the oxidation resistance of total serum lipids was observed (11.4%), while no effect was seen in the LP group (-0.8%) or in the placebo group (-1.0%) (p = 0.007). No differences were observed in the oxidation resistance of VLDL and LDL between the study groups. The phloem also increased in vitro oxidation resistance of serum lipids and radical scavenging activity (DPPH.) in a dose-dependent manner. Our results suggest that polyphenols may inhibit lipid peroxidation in the hydrophilic fraction of serum.

Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.

OBJECTIVE: In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. RESEARCH DESIGN AND METHODS: Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. RESULTS: After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. CONCLUSIONS: Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.

Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes.

OBJECTIVE: The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50-75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA(1c), and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD). RESULTS: Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = -0. 24, P = 0.018) and with maximal IMT (r = -0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS: In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.

Association between carotid intima-media thickness and low-density lipoprotein size and susceptibility of low-density lipoprotein to oxidation in asymptomatic members of familial combined hyperlipidemia families.

BACKGROUND AND PURPOSE: In addition to low-density lipoprotein (LDL) cholesterol, small, dense LDL particles and oxidative modification of LDL have been linked to the pathogenesis of atherosclerosis. The present study was aimed at investigating the association between carotid artery intima-media thickness (IMT) and LDL particle size and susceptibility of LDL to oxidation in vitro in asymptomatic members of familial combined hyperlipidemia (FCHL) families. METHODS: LDL particle size, susceptibility of LDL to oxidation in vitro, and carotid IMT were measured in 148 asymptomatic FCHL family members. RESULTS: LDL particle size and lag time for LDL oxidation were reduced in hyperlipidemic compared with normolipidemic family members. LDL particle size, serum total cholesterol, and alpha-tocopherol in LDL were independently associated with lag time for LDL oxidation in multivariate analysis. LDL particle size was associated with carotid mean IMT independently of clinical, lipid, and antioxidant variables in multivariate analysis. Although the susceptibility of LDL to oxidation in vitro was correlated with mean IMT, it did not have a significant independent contribution to variation in mean IMT in the multivariate model. CONCLUSIONS: We conclude that LDL particle size but not susceptibility of LDL to oxidation in vitro is independently associated with carotid IMT in asymptomatic FCHL family members. These results imply that small, dense LDL as an inherent feature of FCHL is an important diagnostic indicator for coronary artery disease risk in FCHL.

Serum lycopene concentrations and carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies in which high circulating lycopene concentrations were associated with reductions in cardiovascular disease. Lycopene is one of the major carotenoids in the Western diet and is probably one of the protective factors in a vegetable-rich diet. OBJECTIVE: We studied the hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT) would be greater in men with low serum lycopene concentrations. DESIGN: We investigated the relation between serum lycopene concentration and CCA-IMT in 1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in 1991-1993. The subjects were classified into quarters according to serum lycopene concentration. RESULTS: In a covariance analysis with adjustment for covariates, the men in the lowest quarter of serum lycopene concentration had a significantly higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the difference, respectively) than did the other men. The mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. CONCLUSIONS: A low serum lycopene concentration is associated with a higher CCA-IMT in middle-aged men from eastern Finland. This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. Increased thickness of the intima-media has been shown to predict coronary events; thus, lycopene intakes and serum concentrations may have clinical and public health relevance.

A low high density lipoprotein (HDL) level is associated with carotid artery intima-media thickness in asymptomatic members of low HDL families.

Low serum high-density lipoprotein cholesterol (HDL-C) is a strong predictor of coronary heart disease (CHD). The aim of the present study was to evaluate the metabolic parameters predicting the atherosclerotic changes in asymptomatic members of low HDL-C families. We performed carotid B-mode ultrasonography with intima-media thickness (IMT) measurement for 89 asymptomatic members of Finnish low HDL-C families. The family members were categorized as affected or unaffected according to the 10th age-gender specific HDL-C percentile. In the affected group, the most marked decrease of HDL subclasses was observed for HDL2-C when compared with the unaffected (109% difference). In the partial correlation analyses, age and gender showed significant correlations with the mean IMT (for age, r=0.880, P<0.001, and for gender, r=-0.361, P=0.018). Importantly, HDL-C and HDL2-C were significantly inversely related to the mean carotid IMT, also after correction for age (for HDL-C, r=-0.186, P=0.043, for HDL2-C, r=-0.208, P=0.029, when adjusted for age). The correlation for HDL-C was significant also when adjusted for gender. In conclusion, low HDL-C is associated with increased carotid artery IMT in asymptomatic members of low HDL-C families.