Cardiovascular Disease Risk in Overweight and Obese Children with CKD

Chronic kidney disease (CKD) is a leading risk factor for cardiovascular disease among children and young adults. Cardiovascular disease risk factors, both traditional and nontraditional, are highly prevalent in youth with CKD and are associated with a significant burden of intermediate cardiovascular outcomes that include left ventricular hypertrophy (LVH), increased arterial stiffness, and increased carotid intima media thickness.

Identification of the modifiable cardiovascular disease risk factors commonly associated with intermediate outcomes in youth with CKD may aid in the prevention and treatment in that patient population. There are associations between overweight and obesity and traditional cardiovascular disease risk factors among children with mild to moderate CKD. However, there are few data on the impact of adiposity on target-organ damage among children with CKD.

Tammy M. Brady, MD, PhD, and colleagues recently conducted a prospective cohort study to examine the longitudinal association of adiposity with cardiac damage among children with CKD. The study was also designed to examine whether the association was modified by sex. Results of the study were reported in the American Journal of Kidney Diseases [2020;76(2):166-173].

The cohort included children with moderate-to-mild CKD who were enrolled in the CKiD (Chronic Kidney Disease in Children) study at 49 pediatric nephrology centers across North America. The outcome of  interest was age- and sex-specific left ventricular mass index (LVMI) z score and LVH. Mixed-effects models were used in longitudinal analyses to estimate sex-specific associations of body mass index (BMI) z scores with LVMI z score and with LVH, accounting for repeated measurements over time.

The analyses included 725 children for a total of 1483 study visits over 2829 person-years; median follow-up from study entry was 3.3 years. Forty percent (n=286) of the 725 children contributed one visit, 31% (n=228) contributed two visits, 18% (n=127) contributed three visits, 8% (n=60) contributed four visits, and 3% (n=24) contributed five visits.

Of the 725 children in the study, 38% were female and 21% were African American. Echocardiography and BMI were measured concurrently at the first visit. Median age at first visit was 11.0 years, median CKD duration was 8.0 years, and median estimated glomerular filtration rate was 52.6 mL/min/1.73 m². Average blood pressure was in the hypertensive range in 10% of the study population. Nearly one-third of the study cohort was overweight or obese: 13% (n=93) had BMI in the overweight category, in the 85th to <95th age- and sex-specific percentile range; and 16% (n=116) had BMI in the obese category, ≥95th age- and sex-specific percentile. There was no significant difference in the prevalence of overweight or obesity by sex. Median LVMI was 30.5 g/m^2.7                  and median LVMI z score was 0.18. Eleven percent of the study cohort had LVH.

The prevalence of LVH across 1483 study visits by sex in 725 participants across three BMI categories (normal [BMI <85th age- and sex-specific percentile], overweight, and obese), was measured. In girls, the prevalence of LVH was 8.4%  among those in the normal BMI group, 16.0% among those in the overweight group, and 33.7% among those in the obese group. The relationship between BMI and LVH was not as pronounced among boys; the prevalence in each category of BMI was close to 7.0%, which was similar to the overall prevalence of LVH across all visits among boys.

There was an association between each additional year from baseline and both a decrease in LVMI z score (–0.10; 95% confidence interval [CI], –0.12 to –0.08 in unadjusted analysis) and lower odds of LVH (–20%; 95% CI, –11% to –30%) per year.

In multivariable longitudinal analyses, there were significant differences by sex in the association of BMI z score and LVMI z score (P=.01). Among girls, there was an association between each 1-unit greater BMI z score and a 0.38 (95% CI, 0.29-0.47) greater LVMI z score. That association was significantly greater (P=.02) than the 0.24 (95% CI, 0.17-0.31) greater LVMI z score among boys. There was also a significant difference in the association of BMI z score with LVH in girls and boys: for each 1-unit greater BMI z score, girls had a 3.1 (95% CI, 1.8-4.4) times greater odds of LVH, while boys had a 1.5 (95% CI, 1.12-2.1) times greater odds of LVH with each 1-unit greater BMI z score.

Limitations to the study cited by the authors included not all children having repeated measurements, the observational design of the study, and, while LVH is a clinical biomarker for CKD risk, it is a surrogate and not a hard cardiac outcome.

“In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.

“Future studies that focus on enhanced risk stratification strategies and targeted treatment approaches among this at-risk population are needed. Determining the effect of tailored interventions on children with CKD and comorbid obesity will provide more insight into these sex-related differences and establish the effect of weight loss on CV risk,” the researchers said.

Takeaway Points

1. Researchers conducted a prospective cohort study to examine the longitudinal association of adiposity with cardiac damage in children with chronic kidney disease, as well whether the association was modified by sex.
2. The outcome of interest was age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy ((LVH).
3. There was an independent association between adiposity in children and LVMI z score and LVH; the association was stronger in girls than in boys.