The purpose of this study was to examine the roles of adolescence risk factors in predicting coronary artery calcium (CAC).
Elevated coronary heart disease risk factor levels in adolescence may predict subsequent CAC independently of change in risk factor levels from adolescence to adulthood.
CAC was assessed in 589 subjects 40 to 46 years of age from the Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in 1980 (12 to 18 years) and in 2007.
The prevalence of any CAC was 19.2% (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack-years of smoking in adulthood were higher among subjects with CAC than those without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood independently of 27-year changes in these risk factors. The multivariable odds ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95% confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL-C and systolic BP, respectively. Exposure to both of these risk factors in adolescence (defined as values at or above the age- and sex-specific 75th percentile) substantially increased the risk of CAC (multivariable odds ratio: 3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus both risk factors.
Elevated adolescence LDL-C and systolic BP levels are independent predictors of adulthood CAC, indicating that adolescence risk factor levels play an important role in the pathogenesis of coronary heart disease.
Comment In: J Am Coll Cardiol. 2012 Oct 9;60(15):1371-322981554
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
The purpose of this study was to evaluate the hypothesis that high serum levels of ADMA, an indicator of endothelial dysfunction, are associated with an elevated risk of acute coronary events in middle-aged men. To test the hypothesis that lipid lowering medication with statins lowers circulating ADMA levels, we also investigated the effect of simvastatin and atorvastatin treatment on plasma ADMA concentration. In a prospective nested case-control study in 150 middle-aged non-smoking men from Eastern Finland, those who were in the highest quartile for serum ADMA (>0.62 micromol/l) had a 3.9-fold (95% CI: 1.25-12.3, P=0.02) increase in risk of acute coronary events compared with other quartiles. In an 8-week randomised double-blind placebo-controlled trial, plasma ADMA concentrations remained unchanged in simvastatin 80 mg/day (n=16), atorvastatin 40 mg/day (n=16) and placebo (n=16) groups over the study period. Our findings indicate that high serum levels of ADMA, a potential marker for endothelial dysfunction, may increase the risk of acute coronary syndromes. However, aggressive treatment with either simvastatin or atorvastatin did not reduce plasma ADMA levels.
The single nucleotide polymorphism (SNP) rs2995300 in the metalloproteinase-disintegrin gene ADAM8 has been shown to affect the areas of complicated coronary plaques and the risk of fatal myocardial infarction (MI) in men. This study was set up to further investigate the role of ADAM8 in MI.
To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk.
Samples from the Finnish cardiovascular study (FINCAVAS, N=2156) and the angiography and genes study (ANGES, N=1000) were genotyped. Serum sADAM8 concentrations were determined with ELISA (N=443). ADAM8 mRNA levels in atherosclerotic plaques were analysed from the tampere vascular study (TVS, N=53) samples.
A significantly increased MI risk for carriers of the rs2995300C allele and the rs2275725 A allele was revealed in the meta-analysis of the ANGES and FINCAVAS patient data (OR=1.42, P
Using participants (N?=?1733) drawn from the nationally representative longitudinal Young Finns Study (YFS) we estimate the effect of education on depressive symptoms. In 2007, when the participants were between 30 and 45?years old, they reported their depressive symptoms using a revised version of Beck's Depression Inventory. Education was measured using register information on the highest completed level of education in 2007, which was converted to years of education. To identify a causal relationship between education and depressive symptoms we use an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. The genetic risk score was based on 74 genetic variants, which were associated with years of education in a genome-wide association study (GWAS). Because the genetic variants are randomly assigned at conception, they induce exogenous variation in years of education and thus identify a causal effect if the assumptions of the MR approach are met. In Ordinary Least Squares (OLS) estimation years of education in 2007 were negatively associated with depressive symptoms in 2007 (b?=?-0.027, 95% Confidence Interval (CI)?=?-0.040, -0.015). However, the results based on Mendelian randomization suggested that the effect is not causal (b?=?0.017; 95% CI?=?-0.144, 0.178). This indicates that omitted variables correlated with education and depression may bias the linear regression coefficients and exogenous variation in education caused by differences in genetic make-up does not seem to protect against depressive symptoms.
The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization.
Participants (N=2011) were from the on-going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m2) measurements in 2007 and 2011 and genetic information were linked to comprehensive register-based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization and used a genetic score as an instrument for education. The genetic score was based on 74 genetic variants that genome-wide association studies (GWASs) have found to be associated with the years of education. Because the genotypes are randomly assigned at conception, the instrument causes exogenous variation in the years of education and thus enables identification of causal effects.
The years of education in 2007 were associated with lower BMI in 2007/2011 (regression coefficient (b)=-0.22; 95% Confidence Intervals [CI]=-0.29, -0.14) according to the linear regression results. The results based on Mendelian randomization suggests that there may be a negative causal effect of education on BMI (b=-0.84; 95% CI=-1.77, 0.09).
The findings indicate that education could be a protective factor against obesity in advanced countries.
We examined whether quantification of T-wave alternans (TWA) enhances this parameter's capacity to evaluate the risk for total and cardiovascular mortality and sudden cardiac death (SCD).
The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 2,119; 1,342 men and 777 women) with a clinically indicated exercise test with bicycle ergometer. TWA (time domain-modified moving average method) was analyzed from precordial leads, and the results were grouped in increments of 10 microV. Hazard ratios (HR) for total and cardiovascular mortality and SCD were estimated for preexercise, routine exercise, and postexercise stages. Cox regression analysis was performed. During follow-up of 47.1 +/- 12.9 months (mean +/- standard deviation [SD]), 126 patients died: 62 were cardiovascular deaths, and 33 of these deaths were sudden. During preexercise, TWA >or= 20 microV predicted the risk for total and cardiovascular mortality (maximum HR >4.4 at 60 microV, P or=50 microV, with 90 microV TWA yielding maximum HRs for total and cardiovascular death of 3.1 (P = 0.03) and 6.4 (P = 0.002), respectively. During postexercise, TWA >or=60 microV indicated risk for total and cardiovascular mortality, with maximum HR of 3.4 at 70 microV (P = 0.01) for cardiovascular mortality. SCD was strongly predicted by TWA levels >or=60 microV during exercise, with maximum HR of 4.6 at 60 microV (P = 0.002), but was not predicted during pre- or postexercise.
Quantification of TWA enhances its capacity for determination of the risk for total and cardiovascular mortality and SCD in low-risk populations. Its prognostic power is superior during exercise compared to preexercise or postexercise.
The performance of exercise electrocardiography (ECG) for the detection of coronary artery disease (CAD) in women has been limited. The recently developed computerized variable, ST-segment depression/heart rate (ST/HR) hysteresis, has been proved to detect CAD in men more accurately than traditional methods. However, the diagnostic performance of ST/HR hysteresis has not been evaluated in women.
The study population comprised 161 female patients from the Finnish Cardiovascular Study (FINCAVAS). All patients were referred for a routine bicycle exercise test. The maximum values of ST/HR hysteresis, ST/HR index, ST-segment depression at peak exercise (STpeak), at the end of one (ST1rec) and three (ST3rec) minutes of post-exercise were determined. Significant CAD was present in 48, while 65 women showed no angiographic CAD. Also a group of 48 women with low likelihood of CAD (LLC) was formed. Diagnostic performance of variables was assessed by receiver operating characteristic (ROC) analysis. Furthermore, sensitivity values at 80% specificity and specificities at 80% sensitivity were determined.
In a comparison between CAD and LLC groups, the ROC areas for ST/HR hysteresis, ST/HR index, STpeak, ST1rec and ST3rec were 0.89, 0.74, 0.65, 0.84 and 0.73, and sensitivities at 80% specificity were 88%, 67%, 52%, 75% and 60%, respectively. Comparing CAD and no-CAD groups, the ROC areas were 0.73, 0.67, 0.56, 0.63 and 0.60, and specificities at 80% sensitivity were 60%, 38%, 27%, 33% and 30%.
ST/HR hysteresis is a more competent method in CAD detection in women than ST-segment depression or ST/HR index.
Because sudden cardiac death (SCD) is due to cardiac electrical instability, we postulated that prediction of this mode of death by exercise capacity will be enhanced by combined assessment with T-wave alternans (TWA), an index of repolarization abnormality.
The Finnish Cardiovascular Study enrolled consecutive patients (n=2,044) with a routine clinically indicated exercise test. Exercise capacity was measured in metabolic equivalents (METs) and TWA by time-domain modified moving average method.
During 47.2+/-12.8-month follow-up (mean+/-SD) 120 patients died; 58 were cardiovascular deaths, and 29 were SCD. In multivariate analysis after adjustment for sex, age, smoking, use of beta-blockers, as well as other common coronary risk factors, the relative risk of patients whose exercise capacity was depressed (MET or =65 microV) yielded relative risks for SCD of 36.1 (6.3-206.0, P
Elevated blood pressure (BP) in childhood has been associated with increased adult arterial stiffness, the independent predictor of cardiovascular and all-cause mortality. The favorable BP change from childhood to adulthood and the risk of high adult arterial stiffness has not been reported. We examined the effect of child and adult BP on pulse wave velocity (PWV) assessed in adulthood among 1540 white adults followed-up for 27 years since baseline (1980, aged 6-18 years). Childhood elevated BP was defined according to the tables from the National High Blood Pressure Education Program. In adulthood, BP was classified as elevated if systolic BP =120 mm Hg, diastolic BP =80 mm Hg, or self-reported use of antihypertensive medications. PWV was measured in 2007 by whole-body impedance cardiography, and high PWV was defined as values at or above the age-, sex-, and heart rate-specific 80th percentile. Individuals with persistently elevated BP and individuals with normal child but elevated adult BP had increased risk of high adult PWV (relative risk [95% confidence interval], 3.18 [2.22-4.55] and 2.64 [1.79-3.88], respectively) in comparison with individuals with normal (both child and adult) BP. In contrast, individuals with elevated BP in childhood but not in adulthood did not have significantly increased risk of high PWV (relative risk [95% confidence interval], 1.26[0.80-1.99]). The results were consistent when different definitions for child and adult elevated BP were applied. These findings highlight the importance of BP control in the primary prevention of cardiovascular diseases.