Trends in cardiovascular risk factor levels in Finnish children and young adults from the 1970s: The Cardiovascular Risk in Young Finns Study

OBJECTIVES: The Cardiovascular Risk in Young Finns Study is an ongoing multicentre study of atherosclerosis precursors in Finnish children and young adults. The aim of the present report is to describe the secular trends in cardiovascular risk factors between 1980 and 2001 in children and young adults. METHODS: Data on cardiovascular risk factors were collected in a cohort of subjects (original n=3596) that were followed with serial cross-sectional studies from childhood to adulthood. The study was initiated in 1980, and the latest follow-up (after 21 years) was performed in 2001 (with n=2285 participants). To assess secular trends up to the year 2001, selected risk variables were analyzed (ie, total cholesterol, low density lipoprotein [LDL] cholesterol, high density lipoprotein [HDL] cholesterol, triglycerides, apolipoproteins A1 and B, blood pressure, body mass index [BMI] and daily intake of energy and quality of fat) in subjects with complete data for the years 1980, 1986 and 2001 (n=1758). RESULTS: From 1980 to 1986, LDL-cholesterol concentrations decreased 0.32 mmol/L (P<0.0001) in subjects aged 15 to 18 years. From 1986 to 2001, LDL concentrations did not change in 24-year-old subjects (delta=-0.12 mmol/L, P>0.05). HDL-cholesterol concentrations decreased 0.28 mmol/L (P<0.0001) from 1986 to 2001. Triglyceride concentrations increased 0.21 mmol/L (P<0.0001) from 1980 to 1986 and 0.26 mmol/L (P<0.0001) from 1986 to 2001. In female subjects, BMI increased both from 1980 to 1986 (delta=0.5 kg/m(2), P=0.03) and from 1986 to 2001 (delta=1.7 kg/m(2), P=0.0002). Systolic blood pressure levels decreased 3.7 mmHg (P<0.0001) from 1980 to 1986 and 7.0 mmHg (P<0.0001) from 1986 to 2001 in all subjects. CONCLUSION: The authors conclude that between 1986 and 2001, the decreases in LDL-cholesterol concentrations among young adults in Finland stopped. During the same time, HDL-cholesterol concentrations started to decrease, and triglyceride concentrations continued to decrease, and in female subjects, BMI continued to increase. However, also during this time, blood pressure levels continued to decrease in all subjects.     

The prevalence of the metabolic syndrome in young adults. The Cardiovascular Risk in Young Finns Study

OBJECTIVES: The prevalence of the metabolic syndrome is increasing worldwide. We studied its prevalence in Finnish young adults. Three definitions were applied: National Cholesterol Education Program (NCEP), European Group for the Study of Insulin Resistance (EGIR) and International Diabetes Federation (IDF) criteria. We also investigated the secular trend in the metabolic syndrome amongst 24-year-old adults from 1986 to 2001. DESIGN: Population-based follow-up study. SUBJECTS: 2182 healthy young adults (1007 men; 1175 women) aged 24-39 years. MAIN OUTCOME MEASURES: Metabolic syndrome and its components. RESULTS: The prevalence of the metabolic syndrome was 13.0% with NCEP criteria, 9.8% with EGIR criteria and 14.3% with IDF criteria. With NCEP and IDF criteria, the prevalence increased with age in both sexes, but more dramatically in men. There was over sixfold increase in the metabolic syndrome from 4.0% to 25.2% (P < 0.0001) in men between ages 24 and 39 years using the IDF criteria. Increases in obesity and serum triglycerides accounted much for the increase in the prevalence by age. The significant secular trend was seen between years 1986 and 2001 in 24-year-old subjects. The prevalence of the metabolic syndrome increased significantly from 1.0% to 7.5% (P < 0.0001) in 15 years. CONCLUSIONS: There is a substantial increase in the prevalence of the metabolic syndrome in healthy young adults between ages 24 and 39 driven mostly by the increase in obesity. The prevalence of the metabolic syndrome is higher amongst Finnish young adult men compared with women. The secular trend between 1986 and 2001 suggest a dramatic increase in the prevalence of the metabolic syndrome in 24-year-old young adults. Condensed abstract The prevalence of the metabolic syndrome may be increasing in young people. We studied the prevalence of the metabolic syndrome in 2182 young Finnish adults aged 24-39 years using NCEP, EGIR and IDF criteria. The prevalence of the metabolic syndrome was higher amongst Finnish men than women and increased dramatically with age. There was also a dramatic increase in the prevalence of the metabolic syndrome in 24-year-old adults between 1986 and 2001.     

Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study.

AIMS: To study the relations between the metabolic syndrome (MS) and subclinical atherosclerosis in young adults. METHODS AND RESULTS: International Diabetes Federation (msIDF), National Institute of Health Adult Treatment Panel III (msNCEP), and European Group for the Study of Insulin Resistance (msEGIR) definitions of MS were related to carotid artery intima-media thickness (cIMT), brachial flow-mediated dilatation (FMD), and carotid artery compliance (CAC) in 2163 Finnish adults (aged 32 +/- 5years). All definitions associated with increased cIMT and decreased CAC in both sexes. The cIMT values (mean+/-SD) were 0.576 +/- 0.088 mm in subjects without the syndrome, 0.615 +/- 0.102 mm in msIDF, 0.617 +/- 0.104 mm in msNCEP, and 0.607 +/- 0.097 mm in msEGIR (P < 0.0001). Corresponding CAC values were 2.26 +/- 0.72, 1.76 +/- 0.66, 1.73 +/- 0.66, 1.72 +/- 0.66%/10 mmHg (P < 0.001). Impaired brachial FMD was not related to MS but it modified the relations between MS and cIMT: MS correlated with increased cIMT in subjects with an impaired FMD response (P = 0.003) but not in subjects with an enhanced FMD response (P = 0.75). CONCLUSION: All current definitions of MS identify a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis.     

Cardiovascular risk factors and increased carotid intima-media thickness in healthy young adults: the Atherosclerosis Risk in Young Adults (ARYA) Study

BACKGROUND: The relation between cardiovascular risk factors and extent of atherosclerosis in middle-aged and elderly populations is well established. Autopsy studies have suggested that similar associations may be present at a young age. We evaluated the relationship between conventional risk factors and increased carotid intima-media thickness (CIMT) in 750 healthy young adults, aged 27 to 30 years. METHODS: All participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasonographic examination of both common carotid arteries to assess common CIMT (CCIMT). RESULTS: Age (11.2 micro m/SD), body mass index (10.3 micro m/SD), pulse pressure (5.0 micro m/SD), sex (4.8 micro m/SD), and low-density lipoprotein cholesterol level (4.3 micro m/SD) were independent determinants of increased CCIMT in young adults (R2 = 0.36). Total pack-years of smoking, adjusted for age and sex, showed a linear trend with increased CCIMT (P =.02), which attenuated after further adjustment for body mass index. Common CIMT increased gradually and significantly with the number of cardiovascular risk factors present. The estimated absolute risk, based on the Framingham risk function, for development of coronary heart disease within 20 years was 2.5 times higher in individuals with mean CCIMT in the highest quartile compared with those in the lowest quartile of the distribution. CONCLUSIONS: An unfavorable cardiovascular risk profile is associated with a marked increase in CCIMT in young adulthood. Efforts to change modifiable risk factors early in life may retard atherosclerosis development and hence delay the onset of clinical cardiovascular disease later in life.     

Apolipoprotein B is related to arterial pulse wave velocity in young adults: the Cardiovascular Risk in Young Finns Study

ObjectiveLimited data are available regarding the relationship of apolipoproteins B (ApoB) and A-1 (ApoA-1) with arterial stiffness. We conducted the present study to determine whether adulthood ApoB and ApoA-1 are related to arterial pulse wave velocity (PWV). Moreover, we examined whether ApoB and ApoA-1 measured in young adulthood are predictive of PWV assessed 6 years later.MethodsThe study population consisted of 1618 apparently healthy Finnish young adults (aged 30–45 years, 44.9% males) whose apolipoproteins, other cardiovascular risk factors and PWV were measured in 2007. In a sub-sample population, apolipoproteins and other cardiovascular risk factors had also been measured in 2001 (n = 1264). PWV measurements were performed using a whole-body impedance cardiography device.ResultsApoB (p < 0.001) and the ApoB/ApoA-1 ratio (p < 0.001) were directly associated with PWV. ApoB and the ApoB/ApoA-1 ratio measured in young adulthood were also predictive of PWV measured 6 later (p < 0.001 for both). These relations remained significant (p < 0.006) in models adjusted for non-lipid risk factors. The areas under the receiver-operating characteristic (ROC) curves (AUC) were similar for ApoB and non-HDL cholesterol (2001: p for AUC comparison = 0.15; 2007: p for AUC comparison = 0.07) in detecting subjects with increased PWV (PWV ≥ 90th percentile).ConclusionThe present study suggests that elevation of ApoB or non-HDL cholesterol is associated with increased arterial stiffness in young adults.     

Serum amyloid A is independently associated with metabolic risk factors but not with early atherosclerosis: the Cardiovascular Risk in Young Finns Study

Background. Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce. We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis. Methods. Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men). Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima‐media thickness (IMT) and carotid artery compliance, was evaluated with risk‐factor adjusted models. Results. Serum amyloid A correlated directly and independently of BMI with C‐reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men. Use of combined oral contraceptives and intrauterine device was also associated with SAA levels. Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men. SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis. Conclusions. Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance. Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP.     

Distribution and determinants of serum high-sensitive C-reactive protein in a population of young adults: The Cardiovascular Risk in Young Finns Study

OBJECTIVES. Elevated C-reactive protein (CRP) is a suggested risk marker for cardiovascular disease. We aimed at investigating the distribution and determinants of CRP levels in young adults. DESIGN. Population-based study. SUBJECTS. A total of 2,120 participants aged 24-39 years. Main outcome measures. Distribution of CRP, and the relationship between CRP and risk factors. RESULTS. CRP concentration (mean+/-SD) was 1.43+/-3.26 mg L(-1) in men, 1.36+/-2.36 mg L(-1) in women who did not use oral contraceptives (OC) and 3.69+/-6.01 mg L(-1) in women who used OCs. In total, 8.8% of men, 10.3% of non-OC user women and 35.3% of OC user women had CRP concentration >3 mg L(-1) (recommended cut-off point of high risk for cardiovascular disease). In univariate analysis, CRP was associated with obesity indices and physical activity amongst both sexes. In men, the multivariate correlates of CRP included waist circumference (P<0.0001), smoking (<0.0001) and HDL cholesterol (P=0.024) (inverse association). These three variables explained 21.9% (model R(2)) of the total variation in CRP, waist circumference having the greatest influence (partial R(2)=19.6%). In women, the multivariate correlates of CRP included OC use (P<0.0001), body mass index (BMI) (P<0.0001), triglycerides (<0.0001) and physical activity (P=0.025) (inverse association). These four variables explained 38.2% (model R(2)) of the total variation in CRP, with OC use (partial R(2)=18.4%) and BMI (partial R(2)=18.0%) having the greatest influence. CONCLUSIONS. The determinants of CRP level include obesity and smoking in men, and obesity, OC use and physical activity in women. About one in three of healthy women who use OCs have CRP concentration exceeding 3 mg L(-1).     

CYBA C242T gene polymorphism and flow-mediated vasodilation in a population of young adults: the Cardiovascular Risk in Young Finns Study

OBJECTIVE: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion that contributes to decreased nitric oxide bioavailability in the vasculature. The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. We examined the relationship of the C242T polymorphism with endothelial-dependent brachial artery flow-mediated vasodilatation (FMD) in a population-based sample of young healthy adults. METHODS: FMD, defined as the increased percentage in brachial artery diameter after reactive hyperemia, was assessed by ultrasound and the C242T polymorphism using a 5' nuclease assay in 2058 subjects aged 24-39 years. RESULTS: The mean values of brachial artery FMD were 8.0 +/- 4.4% in all study subjects (n = 2058), and 7.8 +/- 4.4, 8.2 +/- 4.5, and 8.7 +/- 4.5% in subjects with the CC (n = 1362), CT (n = 616), and TT (n = 80) genotypes of the C242T CYBA polymorphism, respectively (P = 0.02 for trend). The association remained significant (P = 0.019) in multivariate analyses adjusted for age, sex, obesity indices, smoking habits, blood pressure, serum glucose, lipids, and C-reactive protein. The relationship between FMD and the C242T polymorphism was stronger (P = 0.004) in overweight subjects (body mass index > or = 25 kg/m, n = 895) and ever-smokers (P = 0.008, n = 1082), whereas no relationship was found in normal-weight subjects and non-smokers (P = 0.824 and P = 0.438, respectively). CONCLUSION: The C242T polymorphism of the CYBA gene seems to be related to endothelial function in a population-based sample of young healthy adults. Overweight and smoking status may modify this genetic effect.     

Relation of total and free testosterone and sex hormone-binding globulin with cardiovascular risk factors in men aged 24-45 years. The Cardiovascular Risk in Young Finns Study

BackgroundTotal and free testosterone decrease gradually in men with advancing age but it is not completely known how lower levels of testosterone are related with various cardiovascular risk factors. We studied the levels of total testosterone, calculated free testosterone and sex hormone-binding globulin (SHBG), and their relations with cardiovascular risk factors in young Finnish men.MethodsThe study cohort consisted of 24–45-year-old men participating the Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in 2001 (N = 1024) and 2007 (N = 991). Levels of total testosterone, SHBG, lipids, glucose, insulin, blood pressure and anthropometric factors were measured and free testosterone was calculated.ResultsIn multivariable analyses adjusted for age, body mass index and life-style factors (alcohol consumption, smoking and physical activity), total and calculated free testosterone were inversely correlated with triglycerides (both P < 0.0001), insulin (P = 0.0004 and P = 0.01), systolic blood pressure (P = 0.007 and P = 0.01), and directly with high-density lipoprotein (HDL) cholesterol (P < 0.0001 and P = 0.003). SHBG was inversely correlated with triglycerides and insulin, and directly with HDL-cholesterol (all P < 0.001). In longitudinal analyses, lower levels of testosterone and SHBG were associated with higher levels of triglycerides and insulin six years later (all P < 0.01). Baseline level of SHBG was directly associated with HDL-cholesterol (P < 0.0001).ConclusionIn young and middle-aged men, higher levels of testosterone and SHBG are associated with favourable cardiovascular risk profile characterized by lower levels of triglycerides, insulin and systolic blood pressure, and higher levels of HDL-cholesterol.     

Association of Pathobiologic Determinants of Atherosclerosis in Youth risk score and 15-year change in risk score with carotid artery intima-media thickness in young adults (from the Cardiovascular Risk in Young Finns Study)

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of autopsy findings in subjects 15 to 34 years of age developed a risk score using coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia) to estimate the probability of advanced atherosclerotic lesions in the coronary arteries. The Cardiovascular Risk in Young Finns Study measured coronary heart disease risk factors in a population-based cohort in 1986 and 2001 and measured carotid artery intima-media thickness (IMT) with ultrasonography in 2001. We computed the PDAY risk score from risk factors measured in 1,279 subjects who were 12 to 24 years of age in 1986 and 27 to 39 years of age in 2001. The PDAY risk score early in life (i.e., 1986) and the change in risk score in the following 15 years (i.e., 1986 through 2001) were independent predictors of carotid artery intima-media thickness; the multiplicative effect of 1 point in the 1986 risk score was 1.008 (95% confidence interval 1.005 to 1.012) and the multiplicative effect of a 1-point increase between the 1986 and 2001 risk scores was 1.003 (95% confidence interval 1.001 to 1.006; multiplicative effect of 0.997 for a 1-point decrease). In conclusion, the change in risk score over time (decrease or increase) during adolescence and young adulthood, as well as the risk score early in life, are important predictors of atherosclerosis.     

Associations between serum uric acid and markers of subclinical atherosclerosis in young adults. The cardiovascular risk in Young Finns study

Background and methodsSerum uric acid (SUA) is a suggested biomarker for established coronary artery disease, but the role of SUA in early phases of atherosclerosis is controversial. The relations of SUA with vascular markers of subclinical atherosclerosis, including carotid artery intima-media thickness (cIMT), carotid plaque, carotid distensibility (Cdist) and brachial flow-mediated dilatation (FMD) were examined in 1985 young adults aged 30–45 years. In addition to ordinary regression, we used Mendelian randomization techniques to infer causal associations.ResultsIn women, the independent multivariate correlates of SUA included BMI, creatinine, alcohol use, triglycerides, glucose and adiponectin (inverse association) (Model R² = 0.30). In men, the correlates were BMI, creatinine, triglycerides, C-reactive protein, alcohol use, total cholesterol and adiponectin (inverse) (Model R² = 0.33). BMI alone explained most of the variation of SUA levels both in women and men (Partial R² ～ 0.2). When SUA was modeled as an explanatory variable for vascular markers, it directly associated with cIMT and inversely with Cdist in age- and sex-adjusted analysis. After further adjustments for BMI or glomerular filtration rate, these relations were reduced to non-significance. No associations were found between SUA and FMD or the presence of a carotid plaque. Mendelian randomization analyses using known genetic variants for BMI and SUA confirmed that BMI is causally linked to SUA and that BMI is a significant confounder in the association between SUA and cIMT.ConclusionSUA is associated with cardiovascular risk markers in young adults, especially BMI, but we found no evidence that SUA would have an independent role in the pathophysiology of early atherosclerosis.