Cardiovascular Risk Factors in Childhood and Adulthood and Cardiovascular Disease in Middle Age.

Importance: Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels. Objective: To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach. Design, Setting, and Participants: This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023. Main Outcomes and Measures: The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs. Results: A total of 10 634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period. Conclusions and Relevance: In this cohort study of 10 634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.

Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study.

Background: Studies have shown that cardiovascular health (CVH) is related to depression. We aimed to identify gene networks jointly associated with depressive symptoms and cardiovascular health metrics using the whole blood transcriptome. Materials and methods: We analyzed human blood transcriptomic data to identify gene co-expression networks, termed gene modules, shared by Beck's depression inventory (BDI-II) scores and cardiovascular health (CVH) metrics as markers of depression and cardiovascular health, respectively. The BDI-II scores were derived from Beck's Depression Inventory, a 21-item self-report inventory that measures the characteristics and symptoms of depression. CVH metrics were defined according to the American Heart Association criteria using seven indices: smoking, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol, and fasting glucose. Joint association of the modules, identified with weighted co-expression analysis, as well as the member genes of the modules with the markers of depression and CVH were tested with multivariate analysis of variance (MANOVA). Results: We identified a gene module with 256 genes that were significantly correlated with both the BDI-II score and CVH metrics. Based on the MANOVA test results adjusted for age and sex, the module was associated with both depression and CVH markers. The three most significant member genes in the module were YOD1, RBX1, and LEPR. Genes in the module were enriched with biological pathways involved in brain diseases such as Alzheimer's, Parkinson's, and Huntington's. Conclusions: The identified gene module and its members can provide new joint biomarkers for depression and CVH.

Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study.

BACKGROUND: Lifestyle factors may affect cancer risk. This study aimed to identify whether the American Heart Association ideal cardiovascular health (ICH) score and its individual variables in youth are associated with subsequent cancer incidence. METHODS: This study comprised participants of the Cardiovascular Risk in Young Finns Study free of cancer at the analysis baseline in 1986 (n = 1,873). The baseline age was 12 to 24 years, and the follow-up occurred between 1986 and 2018. RESULTS: Among 1,873 participants (mean age 17.3 ± 4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4 ± 3.4 years). Baseline ICH score was not associated with future cancer risk (HR, 0.96; 95% confidence interval, 0.78-1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence [age- and sex-adjusted HR, 0.45 (0.23-0.88) per 1-category change (nonideal/ideal)] and remained significant in the multivariable-adjusted model, including body mass index, smoking, diet, and socioeconomic status. A continuous PA index at ages 9 to 24 years and moderate-to-vigorous PA in youth were also related to decreased cancer incidence (P < 0.05). Body mass index, smoking, diet, total cholesterol, glucose, and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (P = 0.023). CONCLUSIONS: These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association's ICH score in youth does not. IMPACT: This finding supports efforts to promote a healthy lifestyle and encourages PA during childhood, yielding a subsequent healthier life.

Gene Set Based Integrated Methylome and Transcriptome Analysis Reveals Potential Molecular Mechanisms Linking Cigarette Smoking and Related Diseases.

Advanced integrative analysis of DNA methylation and transcriptomics data may provide deeper insights into smoke-induced epigenetic alterations, their effects on gene expression and related biological processes, linking cigarette smoking and related diseases. We hypothesize that accumulation of DNA methylation changes in CpG sites across genomic locations of different genes might have biological significance. We tested the hypothesis by performing gene set based integrative analysis of blood DNA methylation and transcriptomics data to identify potential transcriptomic consequences of smoking via changes in DNA methylation in the Young Finns Study (YFS) participants (n = 1114, aged 34-49 years, women: 54%, men: 46%). First, we performed epigenome-wide association study (EWAS) of smoking. We then defined sets of genes based on DNA methylation status within their genomic regions, for example, sets of genes containing hyper- or hypomethylated CpG sites in their body or promoter regions. Gene set analysis was performed using transcriptomics data from the same participants. Two sets of genes, one containing 49 genes with hypomethylated CpG sites in their body region and the other containing 33 genes with hypomethylated CpG sites in their promoter region, were differentially expressed among the smokers. Genes in the two gene sets are involved in bone formation, metal ion transport, cell death, peptidyl-serine phosphorylation, and cerebral cortex development process, revealing epigenetic-transcriptomic pathways to smoking-related diseases such as osteoporosis, atherosclerosis, and cognitive impairment. These findings contribute to a deeper understanding of the pathophysiology of smoking-related diseases and may provide potential therapeutic targets.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

The associations of childhood psychosocial factors with cognitive function in midlife-The young finns study.

OBJECTIVE: An adverse psychosocial environment in childhood may harm cognitive development, but the associations for adulthood cognitive function remain obscure. We tested the hypothesis that adverse childhood psychosocial factors associate with poor cognitive function in midlife by leveraging the prospective data from the Young Finns Study. METHOD: At the age of 3-18 years, the participants' psychosocial factors (socioeconomic and emotional environment, parental health behaviors, stressful events, child's self-regulatory behavior, and social adjustment) were collected. In addition to the separate psychosocial factors, a score indicating their clustering was created. Cognitive function was measured at the age of 34-49 years with a computerized test addressing learning and memory (N = 1,011), working memory (N = 1,091), sustained attention and information processing (N = 1,071), and reaction and movement time (N = 999). RESULTS: We observed an inverse association between the accumulation of unfavorable childhood psychosocial factors and poorer learning and memory in midlife (age, sex, education, adulthood smoking, alcohol drinking, and physical activity adjusted ß = -0.032, SE = 0.01, p = .009). This association corresponded approximately to the effect of 7 months aging. Specifically, poor self-regulatory behavior (ß = -0.074, SE = 0.03, p = .032) and social adjustment in childhood (ß = -0.111, SE = 0.03, p = .001) associated with poorer learning ability and memory 30 years later. No associations were found for other cognitive domains. CONCLUSIONS: The findings suggest an association of childhood psychosocial factors with midlife learning ability and memory. If these links are causal, the results highlight the importance of a child's self-regulation and social adjustment as plausible determinants for adulthood cognitive health. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Use of antibiotics and risk of type 2 diabetes, overweight and obesity: the Cardiovascular Risk in Young Finns Study and the national FINRISK study.

PURPOSE: To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity. METHODS: The study sample comprised 2209 (110 with incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24-39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (N = 24,674, 1866 with incident diabetes). RESULTS: Prior antibiotic exposure (> 5 versus 0-1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33-3.96) and FINRISK (HR 1.73; 95%CI 1.51-1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013-1.074) and FINRISK (HR 1.022; 95%CI 1.016-1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m2) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019-1.068) and in FINRISK (OR 1.023; 95%CI 1.018-1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings. CONCLUSION: Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.

Long-term cardiovascular prognosis of patients with type 1 diabetes after myocardial infarction.

BACKGROUND: To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. METHODS: Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005-2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). RESULTS: Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74-2.17; p < 0.0001). Probabilities of cardiovascular death (sHR 1.81; p < 0.0001), recurrent MI (sHR 1.91; p < 0.0001), ischemic stroke (sHR 1.50; p = 0.0003), and heart failure hospitalization (sHR 1.98; p < 0.0001) were higher in patients with type 1 diabetes. Incidence of MACE was higher in diabetes patients than in controls in subgroups of men and women, patients aged < 60 and ≥ 60 years, revascularized and non-revascularized patients, and patients with and without atrial fibrillation, heart failure, or malignancy. CONCLUSIONS: Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.

Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: The relationship between childhood tobacco smoke exposure and cardiac structure and function in midlife is unclear. We investigated the association between parental smoking with cardiac structure and function in adulthood. METHODS: 1250 participants (56.5% female) from the Cardiovascular Risk in Young Finns Study who had data on parental smoking and/or serum cotinine, a biomarker of exposure to tobacco smoke, at baseline 1980 (age 3-18 years) and echocardiography performed in 2011. Parental smoking hygiene (i.e., smoking in the vicinity of children) was categorized by parental smoking and serum cotinine levels in offspring. Dimensions of the left ventricle, diastolic and systolic function, and cardiac remodeling were used as outcomes. Analyses were adjusted for sex, age, and covariates (blood pressure (BP), serum lipids, body mass index, socioeconomic status, smoking (only in adulthood)) in childhood and adulthood. RESULTS: Parental smoking was not associated with systolic or diastolic function in adulthood. Participants exposed to parental smoking (odds ratio (OR) 1.90, 95%CI 1.23-2.92), hygienic parental smoking (OR 1.74, 95%CI 1.12-2.71), and non-hygienic parental smoking (OR 1.88, 95%CI 1.02-3.45) had higher odds of concentric remodeling (relative wall thickness >85th sex-specific percentile without left ventricular hypertrophy). These associations were attenuated after adjustment for child and adult covariates in the non-hygienic parental smoking group. CONCLUSIONS: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population.

Major Lower Limb Amputations and Amputees in an Aging Population in Southwest Finland 2007-2017.

Purpose: The aim of the present study was to describe and analyze changes in the incidences of lower extremity amputations (LEAs), patient characteristics, vascular history of amputees and survival in Southwest Finland. Patients and Methods: This is a retrospective patient study in the Hospital District of Southwest Finland. All consecutive patients with atherosclerosis and diabetes-caused LEA, between 1st January 2007 and 31st December 2017, were included. The annual incidences of major LEA patients were statistically standardized. Patients' diagnoses, functional status, previous revascularizations and minor amputations were recorded, and survival was analyzed. Results: During the 11-year-period major LEAs were performed on 891 patients, 118 (13.2%) were urgent operations. The overall incidence of major LEA was 17.2/100 000 and was age-dependent (3.1 for ≤64 years, 34.3 for 65-74 years, 81.5 for 75-84 years, 216 for ≥85 years). A decrease in incidence was detected in the <65 year-age-group (incidence 4.98 in 2007 and 1.88 in 2017; p = 0.0018). Among older age groups, there was no significant change. Half (50.6%) of all amputees were diabetics. Altogether, 472 patients (53.0%) had a history of revascularization before LEA. 80.1% of index amputations were transfemoral and 19.9% transtibial. Re-surgery was performed on 94 (10.5%) patients. The 1-, 3- and 5-year overall survival were 56%, 30%, and 18%, respectively. Conclusion: Our results suggest that in an aging population, despite good availability of vascular services, a significant number of patients are not fit for active revascularization, and LEA is the only feasible treatment for critical limb ischemia.

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study.

BACKGROUND AND OBJECTIVES: Serum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife. METHODS: Since 2001, participants from the Cardiovascular Risk in Young Finns Study were followed up for 10 years. Serum creatinine was measured repeatedly in 2001, 2007, and 2011. Sex-specific longitudinal trajectories for serum creatinine among participants without kidney disease were identified with latent class growth mixture modeling. Overall cognitive function and 4 specific domains-working memory, episodic memory and associative learning, reaction time, and information processing-were assessed with a computerized cognitive test. RESULTS: Four serum creatinine trajectory groups with clinically normal serum creatinine were identified for both men (n = 973) and women (n = 1,204). After 10 years of follow-up, cognitive testing was performed for 2,026 participants 34 to 49 years of age (mean age 41.8 years). In men and women, consistently low serum creatinine was associated with poor childhood school performance, low adulthood education, low adulthood annual income, low physical activity, and smoking. Compared to the men in the low serum creatinine trajectory group, those in the high serum creatinine group had better overall cognitive performance (ß = 0.353 SD, 95% CI 0.022-0.684) and working memory (ß = 0.351 SD, 95% CI 0.034-0.668), while those in the moderate (ß = 0.247 SD, 95% CI 0.026-0.468) or normal (ß = 0.244 SD, 95% CI 0.008-0.481) serum creatinine groups had better episodic memory and associative learning. No associations were found for women. DISCUSSION: Our results indicate that in men, compared to low serum creatinine levels, consistently high levels may be associated with better memory and learning function in midlife.

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.

Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood: the cardiovascular risk in young Finns study.

PURPOSE: There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. MATERIALS AND METHODS: Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3-18 years, females 54.3%) who had risk factor and lifestyle data available since childhood. Systemic hemodynamics were measured in 2007 (aged 30-45 years) by whole-body impedance cardiography. RESULTS: In the multivariable regression analysis, independent predictors of the adulthood SVRI were childhood BMI, blood glucose, vegetable consumption, smoking, and physical activity (p ≤ .046 for all). Vegetable consumption, smoking, and physical activity remained significant when adjusted for corresponding adult data (p ≤ .036 for all). For the CI, independent predictors in childhood were BMI, systolic blood pressure, vegetable consumption, and physical activity (p ≤ .044 for all), and the findings remained significant after adjusting for corresponding adult data (p ≤ .046 for all). The number of childhood and adulthood risk factors and unfavourable lifestyle factors was directly associated with the SVRI (p < .001) in adulthood. A reduction in the number of risk factors and unfavourable lifestyle factors or a favourable change in BMI status from childhood to adulthood was associated with a lower SVRI in adulthood (p < .001). CONCLUSION: Childhood BMI, blood glucose, vegetable consumption, smoking and physical activity independently predict systemic vascular resistance in adulthood. A favourable change in the number of risk factors or BMI from childhood to adulthood was associated with lower vascular resistance in adulthood.

Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?

OBJECTIVES: To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury. METHODS: Pre-pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study. RESULTS: Measures were strongly correlated at pre- and during-pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre-pregnancy and during-pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits. CONCLUSIONS: Pre- and during-pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.

Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study.

BACKGROUND: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse. SUBJECTS AND METHODS: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30-45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases. RESULTS: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (padj) < 0.05) and 15 suggestively significant (padj < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0). CONCLUSION: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases.

Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study.

We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.

Physical inactivity from youth to adulthood and adult cardiometabolic risk profile.

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3-18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53-0.84; Harmonized criteria), obesity (BMI > 30 kg/m2, RR = 0.76;CI95% = 0.59-0.98), high waist circumference (RR = 0.82;CI95% = 0.69-0.98), and high triglyceride (RR = 0.60;CI95% = 0.47-0.75), insulin (RR = 0.58;CI95% = 0.46-0.74) and glucose (RR = 0.77;CI95% = 0.62-0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLC) concentration (RR = 0.78;CI95% = 0.66-0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk.

Association of Non-High-Density Lipoprotein Cholesterol Measured in Adolescence, Young Adulthood, and Mid-Adulthood With Coronary Artery Calcification Measured in Mid-Adulthood.

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the presence of coronary artery calcification (CAC), a marker of heart disease in adulthood. However, the relative importance of non-HDL-C levels at specific life stages for CAC remains unclear. Objective: To identify the relative association of non-HDL-C measured at distinct life stages (adolescence, young adulthood, mid-adulthood) with the presence of CAC measured in mid-adulthood. Design, Setting, and Participants: The Cardiovascular Risk in Young Finns Study is a population-based prospective cohort study that started in 1980 with follow-up over 28 years. Participants from 3 population centers (Kuopio, Tampere, and Turku in Finland) represent a convenience sample drawn from the 3 oldest cohorts at baseline (aged 12-18 years in 1980). Data were collected from September 1980 to August 2008. Analysis began February 2020. Exposures: Non-HDL-C levels were measured at 3 life stages including adolescence (aged 12-18 years), young adulthood (aged 21-30 years), and mid-adulthood (aged 33-45 years). Main Outcomes and Measures: In 2008, CAC was determined from computed tomography and dichotomized as 0 (no CAC, Agatston score = 0) and 1 (presence of CAC, Agatston score ≥1) for analysis. Using a bayesian relevant life course exposure model, the relative association was determined between non-HDL-C at each life stage and the presence of CAC in mid-adulthood. Results: Of 589 participants, 327 (56%) were female. In a model adjusted for year of birth, sex, body mass index, systolic blood pressure, blood glucose level, smoking status, lipid-lowering and antihypertensive medication use, and family history of heart disease, cumulative exposure to non-HDL-C across all life stages was associated with CAC (odds ratio [OR], 1.50; 95% credible interval [CrI], 1.14-1.92). At each life stage, non-HDL-C was associated with CAC and exposure to non-HDL-C during adolescence had the strongest association (adolescence: OR, 1.16; 95% CrI, 1.01-1.46; young adulthood: OR, 1.14; 95% CrI, 1.01-1.43; mid-adulthood: OR, 1.12; 95% CrI, 1.01-1.34). Conclusions and Relevance: These data suggest that elevated non-HDL-C levels at all life stages are associated with coronary atherosclerosis in mid-adulthood. However, adolescent non-HDL-C levels showed the strongest association with the presence of CAC in mid-adulthood, and greater awareness of the importance of elevated non-HDL-C in adolescence is needed.

Childhood and Adulthood Passive Smoking and Nonalcoholic Fatty Liver in Midlife: A 31-year Cohort Study.

INTRODUCTION: Identifying early life risk factors remains key to the prevention of nonalcoholic fatty liver (hereinafter "fatty liver") in adulthood. However, the longitudinal association of childhood passive smoking with adult fatty liver is not studied. We examined the association of childhood and adulthood passive smoking with fatty liver in midlife. METHODS: This was a 31-year prospective cohort study of 1,315 participants. Information on childhood passive smoking (parental smoking) was collected in 1980 (aged 3-18 years) and 1983 and adulthood passive smoking in 2001, 2007, and 2011. Fatty liver was determined by ultrasound in 2011 (aged 34-49 years). RESULTS: The prevalence of fatty liver was 16.3%. Both childhood and adulthood passive smoking were associated with higher risk of fatty liver, adjusting for potential confounders such as age, sex, childhood socioeconomic status, and adulthood physical activity and alcohol consumption (relative risk = 1.41, 95% confidence interval: 1.01-1.97 for childhood; 1.35, 1.01-1.82 for adulthood). Individuals with persistent exposure to passive smoking between childhood and adulthood had the highest risk (relative risk = 1.99, 95% confidence interval: 1.14-3.45) compared with those without passive smoking in either childhood or adulthood. DISCUSSION: Passive smoking in both child and adult lives are associated with increased risk of adult fatty liver, suggesting that the prevention of passive smoking should start as early as possible and maintain throughout lifetime.