To assess secular trends in serum lipid levels in Finnish children and young adults, the authors examined a total of 3,517, 2,769, 2,392, 352, and 880 subjects who had complete data on serum lipids ...in 1980, 1983, 1986, 1989, and 1992, respectively, in a longitudinal follow-up study. Trend analyses were carried out among subjects aged 15 (n = 1,835) or 18 (n = 1,562) years to exclude the confounding effect of age on the study variables. Data on obesity, physical activity, smoking, and alcohol use were available from each study year, and data on diet were available for the study years 1980, 1986, and 1992. Between 1980 and 1992, mean total cholesterol levels decreased from 4.88 to 4.47 mmol/liter (from 189 to 173 mg/dl), and low density lipoprotein cholesterol levels decreased from 3.06 to 2.85 mmol/liter (from 119 to 110 mg/dl). The mean high density lipoprotein cholesterol levels decreased by 19%, from 1.43 to 1.15 mmol/liter (55.2 to 44.6 mg/dl). During 1986-1992, triglyceride levels increased by 15%, from 0.88 to 1.01 mmol/liter (78.2 to 89.9 mg/dl). During 1980-1992, body mass index values increased from 20.8 to 21.8 kg/m2, parallel to increases in skinfold thickness. In the diet, the ratio of polyunsaturated to saturated fatty acids increased from 0.26 to 0.39. Alcohol and oral contraceptive use became more frequent, and the subjects tended to become less physically active. In conclusion, a change in the lipid profile in Finnish adolescents aged 15 and 18 years and young adults during 1980-1992 was observed, characterized by a decrease in low density lipoprotein cholesterol and high density lipoprotein cholesterol levels and an increase in triglyceride level. Possible determinants for these changes include alterations in diet and a trend toward increased obesity.
The authors studied the occurrence of common lifestyle risk factors, namely, nonprudent diet, smoking, physical inactivity, and frequent inebriation by alcohol in a cohort of young adults aged 18, ...21, and 24 years (n = 484) as part of the Cardiovascular Risk in Young Finns Study in 1986. Risk habits showed significant clustering; the number of subjects was greater than expected in groups with zero and three of four risk habits and less than expected in the group with only one or two risk habits. Stepwise logistic regression analysis was used to find independent determinants for this clustering from a set of socioeconomic, demographic, and behavioral (type A components) determinants. The logistic model suggested several independent risk factors for risk habit clustering. These included male sex, aggressiveness, and past unemployment. Paying a lot of attention to health habits, higher education (being a student), good self-perceived health, and a high sense of responsibility seemed to be protective factors against risk habit clustering. The accumulation of risk habits was also associated with an atherogenic lipid and blood pressure profile (clustering of high density lipoprotein cholesterol/total cholesterol ratio, triglycerides, and diastolic blood pressure in their extreme tertiles). These findings show that common risk habits cluster among young adults. Knowledge about the determinants of this clustering will aid in the planning of future preventive strategies against cardiovascular diseases in young people.
Familial combined hyperlipidemia (FCHL) is characterized by different lipid phenotypes (IIa, IIb, IV) and elevated apolipoprotein B (apo B) levels in affected family members. Despite intensive ...research, the genes involved in the expression of this complex disorder have not been identified, probably because of problems associated with phenotype definition, unknown mode of inheritance, and most probably genetic heterogeneity. To explore the genetics of FCHL in the genetically homogeneous Finnish population, we collected 14 well-documented Finnish pedigrees with premature coronary heart disease and FCHL-like dyslipidemia. The lipolytic enzymes lipoprotein lipase (LPL), hepatic lipase (HL), and hormone-sensitive lipase (HSL) were selected as initial candidate genes because of their central roles in apo B and triglyceride metabolism. On the basis of the pedigree structures, a dominant mode of inheritance was adopted for linkage analyses, and serum total cholesterol and/or triglyceride levels exceeding the 90th percentile level were set as diagnostic criteria (criterion 1). In pairwise linkage analyses with intragenic markers, no evidence for linkage was found. Instead, the significantly negative LOD scores suggested exclusion of all three loci for single major gene effect. LOD scores were -14.63, -5.03, and -5.70 for the three LPL polymorphisms (theta=0.00); -9.40, -6.30, and -4.74 for the three HL polymorphisms (theta=0.00); and -15.29 for the HSL polymorphism (theta=0.00). The results were very similar when apo B levels over the 90th percentile were used as criteria for affected status (criterion 2). Also, when linkage calculations were carried out using an intermediate or recessive mode of inheritance, the results of pairwise linkage analysis remained negative. Furthermore, when haplotypes were constructed from multiple polymorphisms of the LPL and HL genes, no segregation with the FCHL phenotype could be observed in the 14 Finnish families. Data obtained by the affected sib-pair method supported these findings, suggesting that the LPL, HL, or HSL genes do not represent major loci influencing the expression of the FCHL phenotype.
The associations of life-style variables, namely type of dietary fat, alcohol use, smoking, obesity, physical activity and oral contraceptive use with serum lipids, insulin and blood pressure were ...studied in 1398 adolescents and young adults aged 15-24 years. Smokers were more often physically inactive and regular users of alcohol compared to nonsmokers. In females, smoking and alcohol use were more prevalent among oral contraceptive users. Independent effects of life-style variables on lipids, blood pressure and insulin were assessed with multiple linear regression models. In both sexes, body mass index was positively related to low density lipoprotein cholesterol (LDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure and insulin, and negatively with high density lipoprotein cholesterol (HDL-C). Leisure time physical activity was associated with lower levels of insulin among males. Smoking was related with 0.07 mmol/l lower HDL-C levels and about 0.09 mmol/l higher TG levels in males. In both sexes, smoking was related with lower levels of SBP. In males, alcohol use was associated with 0.05 mmol/l higher level of HDL-C (P = 0.06). In females, alcohol use was associated with lower levels of LDL-C and TG. Oral contraceptive use was associated with approximately 0.15 mmol/l higher levels of TG and about 4.0 mmHg higher SBP. Preferring butter over margarine as dietary fat was associated with 0.26 and 0.19 mmol/l higher levels of LDL-C in males and females, respectively. Accumulation of adverse life-habits contributed to the clustering of an atherogenic lipid profile and high blood pressure. In males, those with 4 selected life-habits present, namely obesity, smoking, inactivity and the use of butter, had 5.5 times greater risk (95% confidence interval 1.4-20.7) of belonging to the group with high LDL-C, low HDL-C and high DBP compared to those with zero or one life-habits present. These data demonstrate that life-habits show clustering in adolescents and young adults. Individuals with many adverse life-style risk factors present are at increased risk of having an atherogenic lipid and blood pressure profile.
Familial combined hyperlipidaemia (FCHL) is one of the most common hereditary disorders predisposing to early coronary death. The affected family members have elevations of serum total cholesterol, ...triglycerides or both. Despite intensive research efforts the genetic and metabolic defects underlying this complex disorder are still unknown. To dissect the metabolism and genetics of FCHL the phenotype of an individual must be precisely defined. We assessed the influence of different diagnostic criteria on the phenotype definition and studied factors affecting the phenotype expression in 16 large Finnish families (
n=255) with FCHL. The fractile cut-points used to define abnormal lipid values had a profound influence on the diagnosis of FCHL. If the 90th percentile cut-point was used, approximately 45% of the family members were affected, in concord with the presumed dominant mode of transmission for FCHL. If the 95th percentile was used only 22% of study subjects were affected. To characterize the metabolic differences or similarities between the different lipid phenotypes, we determined very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) particles separated by ultracentrifugation. In linkage analysis no single ultracentrifugation variable could discriminate reliably affected family members from non-affected family members. Our data emphasizes the need for re-evaluation of FCHL diagnostic criteria. Preferably, the diagnosis should be based on a single, reliable metabolic marker.
Clustering and tracking of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C) and diastolic blood pressure were studied in children and young adults. "High-risk" individuals were ...defined as those having these risk factors at the age and sex specific upper tertile (lowest tertile for HDL-C). Among older boys risk factors occurred at adverse levels more often than expected by chance. Cluster-tracking was assessed as the probability of remaining in the extreme tertiles during follow-up. Approximately 25% of subjects initially at "risk" remained there for 6 years. Subjects who became high-risk individuals during the follow-up expressed greater increase in obesity indices, started to consume more saturated fat and cholesterol and became physically active less often compared to those subjects who were initially at risk, but no longer at the follow-up.
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects ...these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesiumintake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001 and insulin -0.020 ln-pmol/L (95% CI:-0.024,-0.017), P < 0.0001. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PUBLICATION ABSTRACT
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects ...these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified
1
) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and
2
) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose β = −0.009 mmol/L (95% CI: −0.013, −0.005),
P
< 0.0001 and insulin −0.020 ln-pmol/L (95% CI: −0.024, −0.017),
P
< 0.0001. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding
TRPM6
showed a nominal association (uncorrected
P
= 0.03) with glucose, and rs11558471 in
SLC30A8
and rs3740393 near
CNNM2
showed a nominal interaction (uncorrected, both
P
= 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of
TRPM6
influence and magnesium interaction with select loci suggests that further investigation is warranted.
Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid disorders. Resistance of adipocytes to the effects of acylation stimulating protein (ASP) may contribute to ...ineffective triglyceride synthesis and thereby prolonged postprandial lipemia and increased fatty acid flux to the liver seen in FCHL patients. Interestingly, ASP is identical to C3a-desArg, fragment of the third component of complement. We examined the relationships between serum levels of complement components C3 and C4 and markers of lipid and glucose metabolism in 11 large FCHL families (
n=53). Median serum C3 levels were 38% higher in affected compared to non-affected male FCHL family members (1.90 g/l vs. 1.38,
P=0.0027). The strongest correlations were observed between serum complement C3 and apolipoprotein B levels, reaching 0.77 in males. These relations were not confounded by obesity or impaired glucose tolerance. In conclusion, serum levels of the main complement components C3 and C4 correlated significantly with serum lipid levels. Further studies are needed to clarify the importance of disturbances in the complement system on the pathogenesis of FCHL and other lipid disorders.
Apolipoprotein E (apo E) determines serum total (TC) and low-density lipoprotein (LDL-C) cholesterol concentrations and is thus associated with coronary heart disease (CHD) risk. We studied if the ...effect of physical activity (PA) on serum TC and LDL-C concentrations varies with apo E phenotype in a population-based sample of children and young adults with regular PA. The study cohort consisted of subjects aged 9, 12, 15, 18, 21, and 24 years in 1986 (N = 1,498) participating in a large multicenter study of cardiovascular risk factors in children and young adults. Serum lipid concentrations were determined enzymatically, and apo E phenotypes by isoelectric focusing and immunoblotting. The composition of the diet was determined by a 48-hour recall method, and a PA index was calculated on the basis of frequency, intensity, and duration of activity assessed by a questionnaire. LDL-C (
P = .0082), TC (
P = .014), and the high-density lipoprotein cholesterol (HDL-C)/TC ratio (
P = .0004) responses to exercise varied with apo E phenotype. The effect of PA on LDL-C, TC, or HDL/TC was not found in apo E phenotype E4/4. A moderate inverse effect of PA on TC and LDL-C and a positive effect on HDL/TC was found in subjects with E4/3 and E3/3 phenotypes. Similar but stronger associations were found between these variables within the group of E3/2 males. The effect of PA on serum lipid levels was strongest within the phenotype E3/2. These associations were not explained by dietary habits. Apo E phenotype partly determines the effect of PA on serum TC and LDL-C in Finnish male children and young adults with regular PA.
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