Boys and those with high systolic blood pressure are particularly at risk

Adolescents and young adults with obesity or type 2 diabetes may be particularly prone to accelerated, early vascular aging, which is particularly prominent in the latter, according to a study published in the Journal of the American Heart Association. In this young cohort, researchers also found several other risk factors for accelerated early vascular aging, including high systolic blood pressure (SBP), age, male sex, and non-white race. Furthermore, each of these seemed to be a key independent risk factor for changes in carotid intima-media thickness (cIMT) and arterial stiffness.

“[T]he normal trajectory of subclinical vascular aging from adolescence into young adulthood has not been well-documented because of relatively small sample sizes in longitudinal studies. Additionally, the key risk factors associated with accelerated early vascular aging are unknown, and need to be identified so that optimized prevention and treatment efforts can be initiated,” wrote Justin R. Ryder, PhD, of the University of Minnesota Medical School, Minneapolis, MN, and fellow researchers.

They conducted a 5-year longitudinal study among 448 adolescents (141 normal-weight; 156 obese; 151 type 2 diabetes). Mean age was 17.6 years, 35.3% of participants were male, and 36.4% were white. At baseline, those with obesity and type 2 diabetes were more likely to be female, non-white, have higher systolic and diastolic blood pressures, and higher total cholesterol, triglycerides, and LDL-C compared with those with normal weight.

To assess early vascular aging, which they defined as a steeper slope of rise in carotid intima-media thickness and arterial stiffness over time, Ryder and colleagues used measures of vascular structure including cIMT (common, internal, and bulb) and arterial stiffness, including carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix).

Adolescents with obesity had a greater positive change in common cIMT (0.05 mm; P ˂ 0.001), bulb cIMT (0.02 mm; P=0.033), internal cIMT (0.03 mm; P ˂ 0.001), and carotid-femoral PWV (0.38 m/sec; P=0.001) compared with participants with normal weight.

Compared with adolescents with normal weight, those with type 2 diabetes demonstrated greater positive changes in common cIMT (0.05; P ˂ 0.001), bulb cIMT (0.06 mm; P ˂ 0.001), internal cIMT (0.04 mm; P ˂ 0.001), Aix (4.67%; P ˂ 0.001), and carotid-femoral PWV (0.74 mm; P ˂ 0.001).

Compared with participants with obesity, those with type 2 diabetes had greater changes in bulb cIMT (0.04 mm; P=0.007), Aix (4.83%; P ˂ 0.001), and carotid-femoral PWV (0.36 m/sec; P=0.009).

Ryder and colleagues also found that higher baseline systolic blood pressure levels were associated with a greater positive change in common cIMT (0.007 mm; P ˂ 0.001), bulb cIMT (0.009 mm; P=0.01), internal cIMT (0.008 mm; P=0.001), and carotid-femoral PWV (0.066 m/sec; P=0.42).

In addition, the following associations were found:

  • Compared with females, male sex with greater positive change in bulb cIMT (0.05 mm; P ˂ 0.001) and carotid stiffness including incremental elastic modulus (cIEM; 128.94 mmHg; P=0.001), and reduced Aix (−3.40%; P ˂ 0.001).
  • Compared with white race, non-white race with a greater positive change in bulb cIMT (0.03 mm; P=0.013).
  • Age with a greater positive change in common cIMT (0.02 mm; P=0.007), bulb cIMT (0.04 mm; P ˂ 0.001), internal cIMT (0.03 mm; P ˂ 0.001), and Aix (3.94%; P ˂ 0.001).

“Our finding of male sex being associated with greater changes in cIMT and arterial stiffness was not unexpected, as males have a higher prevalence of cardiovascular disease than premenopausal women and cIMT increases more rapidly in age- matched males before menopause,” noted researchers.

After adjusting for all risk factors, Ryder et al observed that adolescents with obesity had greater positive changes in common cIMT compared with those with normal weight (0.024 mm; P=0.016).

Compared with those with normal weight, those with type 2 diabetes had greater positive changes in common cIMT (0.032 mm; P=0.006), Aix (3.756% P=0.037), and carotid-femoral PWV (0.43 m/sec; P=0.009). And, compared with participants with obesity, those with type 2 diabetes had greater changes in Aix (5.649%; P ˂ 0.001) and bulb cIMT (0.034 mm; P=0.039).

Researchers also found that higher baseline SBP was associated with greater positive changes in common cIMT (0.007 mm; P ˂ 0.001), bulb cIMT (0.009 mm; P=0.010), internal cIMT (0.008 mm; P=0.010), and carotid-femoral PWV (0.066 m/sec; P=0.042).

Finally, higher baseline LDL-C levels were associated with greater positive changes in carotid-femoral PWV (0.069 m/sec; P=0.011), but reduced cIEM (−27.76 mmHg; P=0.02).

Ryder and colleagues found no statistically significant associations between early vascular aging and heart rate, HDL-C, triglycerides, or C-reactive protein levels.

Limitations of the study include the use of non-invasive measures to assess cardiovascular outcomes, only two follow-up visits over 5 years for each patient, and concurrent treatments to control diabetes, lipids, and blood pressure taken by many participants with type 2 diabetes.

Ryder and colleagues stressed that three of the risk factors they found to be associated with increased vascular risks—obesity, type 2 diabetes, and SBP—are potentially modifiable. Obesity and type 2 diabetes were associated with greater changes in Aix, while SBP was associated with changes in bulb and internal cIMT.

“Obesity and type 2 diabetes mellitus predispose adolescents to greater vascular disease risk and should warrant continued evaluation and treatment to reduce the associated risk,” they concluded. “These data add further evidence underscoring the importance of efforts targeting prevention and treatment of obesity, type 2 diabetes mellitus, and elevated BP among youth with a goal of delaying and/or preventing the progression of early vascular aging.”

  1. In adolescents, obesity and type 2 diabetes may accelerate early vascular aging.

  2. Two key risk factors for accelerated, early vascular aging in adolescents are male gender and high systolic blood pressure.

E.C. Meszaros, Contributing Writer, BreakingMED™

Ryder reports support from Boehringer Ingelheim Pharmaceuticals in the form of drug/placebo.

This study was supported by the National Institutes of Health, the National Center for Research Resources, and the National Center for Advancing Translational Sciences.

Cat ID: 13

Topic ID: 76,13,730,914,13,795,252,192,518,917,918