Skip to main content

Advertisement

You are viewing the new article page. Let us know what you think. Return to old version

Research | Open | Published:

Risk factors for cardiovascular disease and type 2 diabetes retained from childhood to adulthood predict adult outcomes: the Princeton LRC Follow-up Study

International Journal of Pediatric Endocrinologyvolume 2012, Article number: 6 (2012) | Download Citation

Abstract

Background

Pediatric risk factors predict adult cardiovascular disease (CVD) and type 2 diabetes (T2DM), but whether they predict events independently of adult risk factors is not fully known.

Objective

Assess whether risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood.

Study design

770 schoolchildren, ages 5–20 (mean age 12), 26-yr prospective follow-up. We categorized childhood and adult risk factors and 26-year changes (triglycerides [TG], LDL cholesterol, BMI, blood pressure [BP] and glucose ≥, and HDL cholesterol < pediatric and young adult cutoffs). These risk factors and race, cigarette smoking, and family history of CVD and T2DM were assessed as predictors of CVD and T2DM at mean age 38.

Results

Children who had high TG and retained high TG as adults had increased CVD events as adults (p = .0005). Children who had normal BMI and retained normal BMI as adults had reduced CVD events as adults (p = .02). Children who had high BP or high TG and retained these as adults had increased T2DM as adults (p = .0006, p = .003).

Conclusions

Risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood and support universal childhood screening.

Background

Recently, an expert panel recommended screening all American children for risk factors for cardiovascular disease (CVD) [1], not just children of parents with known CVD or high risk factors. Pediatric risk factors for atherosclerosis have been shown to associate with young adult atherosclerotic lesions [2], carotid intima-media thickening (CIMT) [3–7], and cardiovascular disease (CVD) events [8]. Moreover, adolescent CVD risk factor status predicts increased adult CIMT, independent of adult risk factors [9, 10], and children with metabolic syndrome (MetS) have 2–3 times greater risk of high CIMT and type 2 diabetes mellitus (T2DM) as adults versus children free of MetS [11]. Obese children who remained obese as adults have increased type 2 diabetes (T2DM), hypertension, dyslipidemia, and increased CIMT, but risks for these outcomes are attenuated in obese children who became non-obese adults, with outcomes similar to those non-obese in both childhood and adulthood [12].

It is not well understood whether childhood risk factors cause adult CVD directly, independent of adult risk factors, or only in those individuals whose risk factors tracked into adulthood, thereby increasing the length of exposure to high risk factors [10, 13]. The best predictor of high blood pressure (HBP) in adulthood has been reported to be adult obesity or change in obesity; pediatric obesity does not predict adult HBP when adult obesity is in the model [13]. However, HBP is itself a risk factor, not a CVD event. Positive associations between childhood BMI and adult CIMT are generally attenuated once adjusted for adult BMI [14]. Child-adult relationships may be dependent on tracking of BMI from childhood to adulthood [14], since risk of events increases with the length of exposure [15, 16]. There is a stepwise increase in the incidence of T2DM with the duration of obesity [15].

In the current study, our specific aim was to assess whether risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood or whether childhood risk factors are attenuated [12] by changes in risk factors from childhood to young adulthood.

Methods

We used data from the NHLBI Princeton Follow-up Study (PFS, 1999–2003), a 22–30 year follow-up of black and white former schoolchildren first studied in the NHLBI Lipid Research Clinics (LRC, 1973–1976) [8, 17]. PFS collected data following a protocol approved by the Children’s Hospital Institutional Review Board, with signed informed consent [17].

Princeton LRC and PFS studies

The Princeton LRC [18] study was a multistage survey of lipids and other CVD risk factors in students in grades 1–12 and a 50% random sample of their parents by household. The student population in LRC was 72% white and 28% black, with a mean age of 12.3 ± 3.4 years. Participation rates did not differ significantly between races.

The PFS [8] was conducted in adults, 22 to 30 years after their initial pediatric LRC sampling to assess relationships of pediatric risk factors to subsequent adult health events. The subjects’ CVD, T2DM and high blood pressure (HBP) status and use of prescribed medications for lipids, diabetes mellitus, and blood pressure were obtained by questionnaire with an interviewer [8].

After an overnight fast, blood was drawn for measurements of plasma triglyceride (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, and glucose in children and their parents at the LRC assessment and at the subsequent PFS study 26 years later. There was no contact with the former schoolchildren or their parents during the 26-year interval between the LRC and PFS studies.

Diagnosis of CVD, type 2 diabetes and impaired fasting glucose

At PFS, CVD was defined as myocardial infarction, coronary artery bypass graft, angioplasty, ischemic stroke, and carotid or peripheral artery bypass surgery [8]. Diagnosis of diabetes (T2DM) was based on World Organization of Health criteria, fasting glucose ≥ 7 mmol/l (126 mg/dl) and/or self-report of diabetes with treatment by a physician [19]. We excluded from these analyses 10 subjects who had reported type 1 diabetes mellitus as children at LRC. However, in PFS we did not have a measurement of C-peptides or diabetes autoantibody levels, the gold standard methods of distinguishing type 1 from type 2 diabetes [19]. Diagnosis of impaired fasting glucose (IFG) was made when fasting blood glucose was ≥ 100 but <126 mg/dl.

Pediatric and young adult risk factor cutoffs

Pediatric risk factor cutoffs included high LDLC (≥110 mg/dl [2.82 mmol/l]) [20], high BMI (≥85th CDC 2000 age-gender specific percentile), high BP (SBP and/or DBP >90th age-height specific percentiles in current cohort), and cutoffs published for pediatric metabolic syndrome [21]: high TG (≥110 mg/dl [1.24 mmol/l]), low HDLC (≤50 mg/dl [1.28 mmol/l] in girls, ≤40 [1.03 mmol/l] in boys), and high glucose (≥100 mg/dl [5.6 mmol/l]).

Risk factor cutoffs at the PFS were those of the NCEP/AHA Metabolic syndrome (waist ≥ 102 cm men, ≥ 88 cm women, SBP ≥ 130 mmHg and/or DBP ≥ 85, TG ≥ 150 mg/dl [1.69 mmol/l], HDLC <40 mg/dl [1.03 mmol/l] men, <50 mg/dl [1.28 mmol/l] women, glucose ≥ 100 mg/dl [5.6 mmol/l]) [22]. BMI and LDLC cutpoints at the PFS respectively were ≥ 30 kg/m2 (CDC, US Obesity Trends, Trends by State 1985–2009), and the current cohort’s gender-race-specific 90th percentile levels.

Statistical methods

CVD risk factor measures in the cohort in childhood (LRC) and adulthood (PFS) were summarized.

To assess for possible selection bias, comparisons were made between the 770 subjects with complete CVD risk factor measures at both the LRC visit and the PFS visit 26 years later, and 695 subjects without complete measures. Comparisons were made by Wilcoxon test or by chi-square test.

Risk factor measures at LRC and PFS were categorized as high vs. not high (for TG, LDLC, BMI, SBP-DBP, and glucose) or low vs. not low (for HDLC) using the above-mentioned cutoffs. The change in status for each risk factor from LRC to PFS was indicated by 4 dummy variables (normal to normal vs. others; abnormal to normal vs. others; normal to abnormal vs. others; abnormal to abnormal vs. others).

Stepwise logistic regression analysis was used to identify significant independent risk factors for young adult CVD, T2DM and IFG at PFS in multivariate analyses. Explanatory variables included age at follow-up and categorical variables: race, pediatric and young adult risk factor status group (high vs. not high) for TG, LDLC, BMI, glucose, blood pressure, HDLC (low vs. not low), cigarette smoking (yes vs. no), and parental history (yes vs. no) of CVD or T2DM, as well as changes in risk factor status from childhood to young adulthood. Including only significant explanatory variables from stepwise selection, logistic regression models were re-evaluated allowing more observations to be used.

From the logistic regression model, the changes in TG, BMI or BP from LRC to PFS were significant predictors for the CVD or T2DM at PFS. The associations of these risk factor changes with CVD or T2DM status were graphed. Pediatric to adult changes in risk factors were ordered to represent increasing risk, with lowest risk being normal to normal, then abnormal to normal, normal to abnormal and highest being abnormal to abnormal. The Mantel-Haenszel test was used to measure the significance of associations between the risk factor status groups in childhood and adulthood and the adult development of CVD or T2DM.

Results

In the LRC study, there were 1465 subjects eligible for the PFS, and 909 subjects were studied in PFS 26 years later (follow-up rate 62%). Of these 909 subjects, complete data (required for the resultant logistic model) was available in 770 (85%), Table 1. Compared with the 695 eligible subjects not included in the current report, BMI was higher in the sampled group (20.1 ± 4.3 vs 19.2 ± 4.2 kg/m2, p < .0001), but there were no differences (p > 0.05) in TG, HDLC, LDLC, SBP and DBP at the LRC visit. In the sampled group, percent white was higher 73% vs 66% (p = .008), and percent male was lower 46% vs 57% (p < .0001).

Table 1 Risk factors for cardiovascular disease and type 2 diabetes mellitus, measured during childhood (LRC) and 26 years later in young adulthood (PFS) in 770 subjects
Full size table

Pediatric and adult CVD risk factor measures 26 years later were highly correlated, Table 1. Twenty-six of the 770 subjects (3.4%) were taking cholesterol-lowering medications at their PFS visit, Table 1. Excluding their LDLC values from the analyses of correlations between LRC and PFS did not appreciably affect the correlation coefficients, Table 1. After adjusting for BMI at mean ages 12 and 38, age 12 and age 38 risk factors remained closely correlated, Table 1.

High TG in childhood retained into adulthood characterized the 19 subjects who had CVD in adulthood, while normal TG at both visits characterized the 751 subjects free of CVD at the PFS visit, Figure 1. There were 55 subjects with high TG at both visits, of whom 8 (14.6%) had CVD compared to 5 of 490 with normal TG at both visits (1%) for a risk ratio of 14.6 to 1, Figure 1, Table 2. The incidence of CVD was 1.9% in subjects with high TG at LRC but normal TG at PFS, and 2.9% in subjects with normal TG at LRC but high TG at PFS. Thus, there was a linear trend for CVD across the four TG classification groups (p < .0001), Table 2.

Figure 1
figure1

Changes in TG status groups from childhood to adulthood by adult CVD status.

Full size image
Table 2 Incidence rate (%) of cardiovascular disease (CVD) by triglyceride (TG) and BMI classification in childhood and adulthood and of type 2 diabetes mellitus (T2DM) by blood pressure and triglyceride classification in childhood and adulthood
Full size table

Normal BMI in childhood retained into adulthood characterized the 751 subjects free of CVD at the PFS visit, while high BMI in childhood retained into adulthood characterized the 19 subjects who had adult CVD, Figure 2. There were 113 subjects with high BMI at both visits, of whom 7 (6.2%) had CVD and 427 with normal BMI at both visits of whom 4 had CVD (0.9%) for a risk ratio of 6.9 to 1. The incidence of CVD was 2.5% in subjects with high BMI at LRC but normal BMI at PFS, and 4.0% in subjects with normal BMI at LRC but high TG at PFS. Thus, there was a linear trend for CVD across the four BMI classification groups (p = .0005), 2.

Figure 2
figure2

Changes in BMI status groups from childhood to adulthood by adult CVD status.

Full size image

High blood pressure retained from childhood to adulthood was much more common in the 29 subjects who had adult T2DM (28%) than in the 417 free of adult T2DM (5%), while normal childhood blood pressure retained into adulthood characterized the 417 subjects free of T2DM at the PFS visit (65%), Figure 3. The incidence of T2DM was 28.6% in subjects with high BP at LRC and PFS compared to 3.6% in subjects with normal BP at both LRC and PFS, for a relative risk of 8 to 1. The one of 22 subjects with high BP at LRC but normal BP at PFS did have T2DM so the incidence rate was 4.6%. In subjects with normal BP at LRC but high BP at PFS the incidence of T2DM was 8.6%. Thus, there was a linear trend for T2DM across the four BP classification groups (p < .0001), Table 2.

Figure 3
figure3

Changes in BP status groups from childhood to adulthood by adult T2DM status.

Full size image

High TG retained from childhood to adulthood was much more common in subjects who developed T2DM as adults (31%) than in those free of T2DM (6%), Figure 4. The incidence of T2DM was 27.3% in subjects with high TG at LRC and PFS compared to 3.8% in subjects with normal TG at both LRC and PFS, for a relative risk of 7.1. No person with high TG at LRC but normal TG at PFS had T2DM, incidence rate = 0.0%. In subjects with normal TG at LRC but high TG at PFS the incidence of T2DM was 9.6%. Thus, there was a linear trend for T2DM across the four TG change classification groups (p < .0001), Table 2.

Figure 4
figure4

Changes in TG status groups from childhood to adulthood by adult T2DM status.

Full size image

By stepwise logistic regression, adult CVD (19 yes, 751 no) was independently and significantly associated with high childhood TG retained adulthood (p = .0005) and with age at follow-up (p = .0009), and was inversely associated with normal BMI from childhood retained into adulthood, p = .02, Table 3.

Table 3 Childhood (LRC) and adulthood (PFS) predictors for cardiovascular disease (CVD), type 2 diabetes (T2DM) and impaired fasting glucose (IFG) at PFS
Full size table

Adult T2DM (29 yes, 417 no) was associated with BP and TG high in childhood and retained into adulthood (p = .0006, .003), with childhood glucose (p = .006), with adult age (p = .002), and with black race (p = .04), Table 3.

Adult IFG (88 yes, 617 no) was positively associated with adult BP and TG (high vs not high), p < .0001, p = .0009, respectively, and with cigarette smoking, p = .018, Table 3.

Neither pediatric nor young adult LDLC was associated with young adult CVD, p > .05.

Discussion

In the current study, risk factors for CVD retained from childhood to adulthood predicted CVD in young adulthood. Risk for CVD was attenuated when childhood risk factors were not maintained into adulthood, congruent with the report by Juonala et al. [12]. Children who had high TG and retained high TG as adults had increased CVD events. Children who had normal BMI and retained normal BMI as adults had reduced CVD events. Children who had high childhood BP and TG and retained these into adulthood were more likely to have adult T2DM, children with childhood risk factors not retained were not associated with increased adult T2DM, congruent with the report by Juonala et al. [12].

In contrast to CVD and T2DM, adult IFG was associated with adult high BP, TG, and cigarette smoking, and was not associated with retention of risk factors from childhood to adulthood.

Our finding of a significant association of high TG retained from childhood to adulthood with young adult CVD is consistent with pediatric [8] and adult studies where non-fasting [23–25] and fasting TG [26–29] are independent risk factors for CVD and for ischemic stroke [30]. The association of TG high from childhood through young adulthood with adult CVD may, speculatively, reflect the presence of pediatric metabolic syndrome, a known predictor of adult CVD [18]. Moreover, TG levels in adolescent males have been related to coronary artery calcification 15 to 20 years later in young adults [31]. Coronary artery streaks in 6 to 30 year olds are significantly correlated with antecedent TG and very low density lipoprotein cholesterol [32, 33]. In a post-mortem study of 15 to 34 year old men, the percentage of the right coronary arterial intima involved with atherosclerosis correlated with a combination of LDL and VLDL cholesterol levels, and was inversely associated with HDL cholesterol [34].

Normal childhood BMI retained to adulthood was a significant negative risk factor for adult CVD. The association of normal BMI retained from childhood to adulthood with low young adult CVD events is consistent with the report by Chen et al. [35] where clustering of bottom quartile BMI, HOMA IR, SBP, and the ratio of total/HDL cholesterol was associated with decreasing mean values of carotid intima-media thickness in adulthood.

High childhood BP and TG, two components of the metabolic syndrome complex, retained into adulthood were associated with adult T2DM, findings broadly in agreement with those of Everhart et al. [15] and Lee et al. [16], which suggested that the duration of the risk factor presence from childhood to young adulthood and the cumulative exposure to risk factors predict adult outcomes.

Our finding of an association of glucose levels in childhood with the development of T2DM in adulthood is consistent with a recent report from the Bogalusa Heart Study that fasting plasma glucose in childhood is a predictor of T2DM in young adulthood even when the pediatric glucose is within the normal range [36]. Moreover, childhood insulin response during an oral glucose challenge predicts adult acute insulin response [37].

Given the significant tracking of risk factors for CVD and T2DM as observed in the current and previous studies [11, 38–40], failure to act on such childhood risk factors high TG, high BP, and obesity [12, 16] means the underlying pathology may continue into young adulthood, increasing the likelihood of an adverse outcome [10, 41]. These findings emphasize the importance of risk factor screening in childhood [1]. Lifestyle [1] and pharmacologic intervention [1, 42, 43] in childhood-adolescence might prevent development of CVD or T2DM in young adulthood.

A weakness in the current study is the absence of knowledge concerning when (at what age) participants with normal factors in childhood developed abnormal risk factors and when participants with abnormal factors in childhood developed normal risk factors. Thus, it was not possible to evaluate more precisely the length of time the at-risk state existed.

In the current study, neither pediatric nor young adult LDLC was associated with young adult CVD, perhaps attributable to treatment of high LDLC in 26 of 770 (3. 4%) young adults at PFS, or to the fact that with only 19 CVD endpoints by mean age 38, the study may not have had adequate power to declare an LDLC effect significant. Treatment to lower LDLC might, speculatively, also have reduced the power of LDLC to predict CVD.

Conventionally, parental history of CVD serves as an indication for screening for lipid abnormalities in children [44, 45]. After detailed review of basing childhood screening on parental history, the recent Expert Panel statement [1] called for universal risk factor screening in children [1]. Identification of CVD risk factors in a child can directly facilitate primary prevention [1] in the child through young adulthood, and also focus diagnostic attention on the potentially high-risk parent.

Conclusions

Risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood and support universal childhood screening.

Abbreviations

LRC:

Lipid Research Clinics

PFS:

Princeton School Follow-up Study

CVD:

cardiovascular disease

CHD:

coronary heart disease

CIMT:

carotid intima-media thickening

IFG:

impaired fasting glucose

T2DM:

type 2 diabetes mellitus

HBP:

high blood pressure

DBP:

diastolic blood pressure

SBP:

systolic blood pressure

TG:

triglyceride

MetS:

metabolic syndrome

HDLC:

high density lipoprotein cholesterol

LDLC:

low density lipoprotein cholesterol

BMI:

body mass index

NCEP:

National Cholesterol Education Program

NHLBI:

National Heart, Lung, and Blood Institute

AHA:

American Heart Association.

References

  1. 1.

    Expert panel on integrated guicelines for cardiovascular health and risk reduction in children and adolescents: Summary Report. Pediatrics. 2011, 128 (Supplement 5): S1-S45.

  2. 2.

    McMahan CA, Gidding SS, Malcom GT, Tracy RE, Strong JP, McGill HC: Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis. Pediatrics. 2006, 118: 1447-1455. 10.1542/peds.2006-0970.

  3. 3.

    Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, Chen W, Srinivasan SR, Daniels SR, Kahonen M, Laitinen T, Taittonen L, Berenson GS, Viikari JS, Raitakari OT: Influence of age on associations between childhood risk factors and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010, 122: 2514-2520. 10.1161/CIRCULATIONAHA.110.966465.

  4. 4.

    Juonala M, Viikari JS, Kahonen M, Taittonen L, Laitinen T, Hutri-Kahonen N, Lehtimaki T, Jula A, Pietikainen M, Jokinen E, Telama R, Rasanen L, Mikkila V, Helenius H, Kivimaki M, Raitakari OT: Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study. Eur Heart J. 2010, 31: 1745-1751. 10.1093/eurheartj/ehq141.

  5. 5.

    Magnussen CG, Venn A, Thomson R, Juonala M, Srinivasan SR, Viikari JS, Berenson GS, Dwyer T, Raitakari OT: The association of pediatric low- and high-density lipoprotein cholesterol dyslipidemia classifications and change in dyslipidemia status with carotid intima-media thickness in adulthood evidence from the cardiovascular risk in Young Finns study, the Bogalusa Heart study, and the CDAH (Childhood Determinants of Adult Health) study. J Am Coll Cardiol. 2009, 53: 860-869. 10.1016/j.jacc.2008.09.061.

  6. 6.

    Freedman DS, Dietz WH, Tang R, Mensah GA, Bond MG, Urbina EM, Srinivasan S, Berenson GS: The relation of obesity throughout life to carotid intima-media thickness in adulthood: the Bogalusa Heart Study. Int J Obes Relat Metab Disord. 2004, 28: 159-166.

  7. 7.

    Davis PH, Dawson JD, Riley WA, Lauer RM: Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study. Circulation. 2001, 104: 2815-2819. 10.1161/hc4601.099486.

  8. 8.

    Morrison JA, Glueck CJ, Horn PS, Yeramaneni S, Wang P: Pediatric triglycerides predict cardiovascular disease events in the fourth to fifth decade of life. Metabolism. 2009, 58: 1277-1284. 10.1016/j.metabol.2009.04.009.

  9. 9.

    Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Maki-Torkko N, Jarvisalo MJ, Uhari M, Jokinen E, Ronnemaa T, Akerblom HK, Viikari JS: Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003, 290: 2277-2283. 10.1001/jama.290.17.2277.

  10. 10.

    Daniels SR: Can lipid and lipoprotein concentrations in childhood predict adult atherosclerosis?. J Am Coll Cardiol. 2009, 53: 870-871. 10.1016/j.jacc.2008.11.037.

  11. 11.

    Magnussen CG, Koskinen J, Chen W, Thomson R, Schmidt MD, Srinivasan SR, Kivimaki M, Mattsson N, Kahonen M, Laitinen T, Taittonen L, Ronnemaa T, Viikari JS, Berenson GS, Juonala M, Raitakari OT: Pediatric metabolic syndrome predicts adulthood metabolic syndrome, subclinical atherosclerosis, and type 2 diabetes mellitus but is no better than body mass index alone: the Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study. Circulation. 2010, 122: 1604-1611. 10.1161/CIRCULATIONAHA.110.940809.

  12. 12.

    Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, Srinivasan SR, Daniels SR, Davis PH, Chen W, Sun C, Cheung M, Viikari JS, Dwyer T, Raitakari OT: Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med. 2011, 365: 1876-1885. 10.1056/NEJMoa1010112.

  13. 13.

    Lauer RM, Clarke WR: Childhood risk factors for high adult blood pressure: the Muscatine Study. Pediatrics. 1989, 84: 633-641.

  14. 14.

    Lloyd LJ, Langley-Evans SC, McMullen S: Childhood obesity and adult cardiovascular disease risk: a systematic review. Int J Obes (Lond). 2010, 34: 18-28. 10.1038/ijo.2009.61.

  15. 15.

    Everhart JE, Pettitt DJ, Bennett PH, Knowler WC: Duration of obesity increases the incidence of NIDDM. Diabetes. 1992, 41: 235-240. 10.2337/diabetes.41.2.235.

  16. 16.

    Lee J, Gebremariam A, Vijan S, Gurney JG: Excess body mass index-years, a measure of degree and duration of excess weight and risk for incident diabetes. Archives of Pediatrics and Adolescent Medicine. 2011, 166 (1): 42-48.

  17. 17.

    Morrison JA, Friedman LA, Wang P, Glueck CJ: Metabolic syndrome in childhood predicts adult metabolic syndrome and type 2 diabetes mellitus 25 to 30 years later. J Pediatr. 2008, 152: 201-206. 10.1016/j.jpeds.2007.09.010.

  18. 18.

    Morrison JA, Friedman LA, Gray-McGuire C: Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics. 2007, 120: 340-345. 10.1542/peds.2006-1699.

  19. 19.

    Dabelea D, Bell RA, D'Agostino RB, Imperatore G, Johansen JM, Linder B, Liu LL, Loots B, Marcovina S, Mayer-Davis EJ, Pettitt DJ, Waitzfelder B: Incidence of diabetes in youth in the United States. JAMA. 2007, 297: 2716-2724.

  20. 20.

    Magnussen CG, Raitakari OT, Thomson R, Juonala M, Patel DA, Viikari JS, Marniemi J, Srinivasan SR, Berenson GS, Dwyer T, Venn A: Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study. Circulation. 2008, 117: 32-42. 10.1161/CIRCULATIONAHA.107.718981.

  21. 21.

    Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH: Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med. 2003, 157: 821-827. 10.1001/archpedi.157.8.821.

  22. 22.

    Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Spertus JA, Costa F: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Curr Opin Cardiol. 2006, 21: 1-6. 10.1097/01.hco.0000200416.65370.a0.

  23. 23.

    Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM: Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007, 298: 309-316. 10.1001/jama.298.3.309.

  24. 24.

    McBride PE: Triglycerides and risk for coronary heart disease. JAMA. 2007, 298: 336-338. 10.1001/jama.298.3.336.

  25. 25.

    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A: Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007, 298: 299-308. 10.1001/jama.298.3.299.

  26. 26.

    Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V: Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007, 115: 450-458. 10.1161/CIRCULATIONAHA.106.637793.

  27. 27.

    Austin MA, McKnight B, Edwards KL, Bradley CM, McNeely MJ, Psaty BM, Brunzell JD, Motulsky AG: Cardiovascular disease mortality in familial forms of hypertriglyceridemia: a 20-year prospective study. Circulation. 2000, 101: 2777-2782. 10.1161/01.CIR.101.24.2777.

  28. 28.

    Kannel WB, Vasan RS: Triglycerides as vascular risk factors: new epidemiologic insights. Curr Opin Cardiol. 2009, 24: 345-350. 10.1097/HCO.0b013e32832c1284.

  29. 29.

    Onat A, Sari I, Yazici M, Can G, Hergenc G, Avci GS: Plasma triglycerides, an independent predictor of cardiovascular disease in men: a prospective study based on a population with prevalent metabolic syndrome. Int J Cardiol. 2006, 108: 89-95. 10.1016/j.ijcard.2005.06.056.

  30. 30.

    Varbo A, Nordestgaard BG, Tybjaerg-Hansen A, Schnohr P, Jensen GB, Benn M: Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population. Ann Neurol. 2011, 69: 628-634. 10.1002/ana.22384.

  31. 31.

    Mahoney LT, Burns TL, Stanford W, Thompson BH, Witt JD, Rost CA, Lauer RM: Coronary risk factors measured in childhood and young adult life are associated with coronary artery calcification in young adults: the Muscatine Study. J Am Coll Cardiol. 1996, 27: 277-284.

  32. 32.

    Berenson GS, Wattigney WA, Tracy RE, Newman WP, Srinivasan SR, Webber LS, Dalferes ER, Strong JP: Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study). Am J Cardiol. 1992, 70: 851-858. 10.1016/0002-9149(92)90726-F.

  33. 33.

    Newman WP, Freedman DS, Voors AW, Gard PD, Srinivasan SR, Cresanta JL, Williamson GD, Webber LS, Berenson GS: Relation of serum lipoprotein levels and systolic blood pressure to early atherosclerosis. The Bogalusa Heart Study. N Engl J Med. 1986, 314: 138-144. 10.1056/NEJM198601163140302.

  34. 34.

    Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA. 1990, 264: 3018-3024.

  35. 35.

    Chen W, Srinivasan SR, Li S, Xu J, Berenson GS: Metabolic syndrome variables at low levels in childhood are beneficially associated with adulthood cardiovascular risk: the Bogalusa Heart Study. Diabetes Care. 2005, 28: 126-131. 10.2337/diacare.28.1.126.

  36. 36.

    Nguyen QM, Srinivasan SR, Xu JH, Chen W, Berenson GS: Fasting plasma glucose levels within the normoglycemic range in childhood as a predictor of prediabetes and type 2 diabetes in adulthood: the Bogalusa Heart Study. Arch Pediatr Adolesc Med. 2010, 164: 124-128. 10.1001/archpediatrics.2009.268.

  37. 37.

    Thearle MS, Bunt JC, Knowler WC, Krakoff J: Childhood predictors of adult acute insulin response and insulin action. Diabetes Care. 2009, 32: 938-943. 10.2337/dc08-1833.

  38. 38.

    Nicklas TA, von Duvillard SP, Berenson GS: Tracking of serum lipids and lipoproteins from childhood to dyslipidemia in adults: the Bogalusa Heart Study. Int J Sports Med. 2002, 23 (Suppl 1): S39-S43.

  39. 39.

    Eisenmann JC, Welk GJ, Wickel EE, Blair SN: Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study. Am J Hum Biol. 2004, 16: 690-696. 10.1002/ajhb.20079.

  40. 40.

    Webber LS, Srinivasan SR, Wattigney WA, Berenson GS: Tracking of serum lipids and lipoproteins from childhood to adulthood. The Bogalusa Heart Study. Am J Epidemiol. 1991, 133: 884-899.

  41. 41.

    Nadeau KJ, Maahs DM, Daniels SR, Eckel RH: Childhood obesity and cardiovascular disease: links and prevention strategies. Nat Rev Cardiol. 2011, 8: 513-525. 10.1038/nrcardio.2011.86.

  42. 42.

    Manlhiot C, Larsson P, Gurofsky RC, Smith RW, Fillingham C, Clarizia NA, Chahal N, Clarke JT, McCrindle BW: Spectrum and management of hypertriglyceridemia among children in clinical practice. Pediatrics. 2009, 123: 458-465. 10.1542/peds.2008-0367.

  43. 43.

    McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, Hayman LL, Daniels SR: Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation. 2007, 115: 1948-1967. 10.1161/CIRCULATIONAHA.107.181946.

  44. 44.

    Schwandt P, Haas GM, Liepold E: Lifestyle and cardiovascular risk factors in 2001 child–parent pairs: the PEP Family Heart Study. Atherosclerosis. 2010, 213: 642-648. 10.1016/j.atherosclerosis.2010.09.032.

  45. 45.

    Dennison BA, Kikuchi DA, Srinivasan SR, Webber LS, Berenson GS: Parental history of cardiovascular disease as an indication for screening for lipoprotein abnormalities in children. J Pediatr. 1989, 115: 186-194. 10.1016/S0022-3476(89)80063-0.

Download references

Acknowledgements

Supported by American Heart Association (National) 9750129 N and NIH-HL62394 (Dr Morrison), Lipoprotein Research Fund of the Jewish Hospital of Cincinnati (Dr Glueck).

Author information

Affiliations

  1. From the Division of Cardiology, Children’s Hospital of Cincinnati, 3333 Burnet Avenue, 45229, Cincinnati, USA

    • John A Morrison
    •  & Jessica G Woo

  2. From the Cholesterol and Metabolism Center, Jewish Hospital of Cincinnati, Cincinnati, USA

    • Charles J Glueck
    •  & Ping Wang

  3. Cholesterol Center, UC Health Business Center, 3200 Burnet Avenue, Cincinnati, OH, 45229, USA

    • Charles J Glueck

Authors

  1. Search for John A Morrison in:

  2. Search for Charles J Glueck in:

  3. Search for Jessica G Woo in:

  4. Search for Ping Wang in:

Corresponding author

Correspondence to Charles J Glueck.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

JAM and CJG designed the study. JAM supervised the initial study in children and the prospective follow-up study in young adulthood. CJG, JAM, and PW edited, analyzed, and assessed the data. PW provided the major biostatistical expertise, JAM, the major epidemiologic expertise. All authors read and approved the final manuscript.

Authors’ original submitted files for images

Authors’ original file for figure 1

Authors’ original file for figure 2

Authors’ original file for figure 3

Authors’ original file for figure 4

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Risk factors
  • Cardiovascular disease
  • Type 2 diabetes mellitus
  • Obesity
  • High blood pressure
  • Tracking

International Journal of Pediatric Endocrinology

ISSN: 1687-9856

Contact us