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Elevated low-density lipoprotein in childhood highlights the need for early risk screening

23rd July 2021

An analysis of low-density lipoprotein levels in children found similar levels at ages 9 and 18, indicating the importance of early screening.

Elevated levels of low-density lipoprotein cholesterol (LDL-C) leads to the development of atherosclerosis and is a risk factor for cardiovascular disease. Some evidence suggests an association between childhood obesity and the subsequent risk of biochemical abnormalities in adults. Nevertheless, there is a lack of longitudinal data linking the presence of childhood cardiovascular risk factors with adult disease. Furthermore, little is known about the extent to which risk factors such as LDL-C levels vary during childhood and how this might contribute towards atherosclerosis and adverse cardiovascular outcomes in adult life. A better understanding the childhood trajectories of LDL-C cholesterol could lead to improved preventative strategies. In trying to shed more light on this topic, a team from the Division of General Medicine, Columbia University, Irving Medical Centre, New York, turned to data available in the International Childhood Cardiovascular Cohort (i3C) Consortium. While children virtually never experience adverse cardiovascular events, the i3C is the first longitudinal cohort study designed to locate adults with detailed and repeated childhood biological, and physical measurements and includes over 10,000 individuals from several countries. The Irving Medical Centre team used data from i3C individuals who had at least one LDL-C measurement between the ages of 3 and 17 years of age and extracted demographic and body mass index information from these participants. The team considered LDL-C levels greater than 160mg/dl (4.14mmol/l) as consistent with probable familial hypercholesterolaemia (FH) and used the more stringent criteria of an LDL-C of greater than 160mg/dl on at least two occasions and a level of LDL-C of 190mg/dl or greater as a threshold for FH. In order to examine LDL-C trajectories during childhood, the team fitted a linear model of LDL-C against age, adjusting for sex, ethnicity and body mass index.

Findings
A total of 15,045 children with a mean age of 9.9 years (48.7% male) were included in the analysis. Overall, 2.8% of children had an LDL-C greater than 160mg/dl and 0.6% had values exceeding 190mg/dL. Using the more stringent criteria, 1% of children had elevated LDL-C levels (> 160mg/dL) on two occasions and 0.3%, levels above 190mg/dl, consistent with FH. Using the linear model it could be seen that mean LDL-C cholesterol levels increased from age 3 to 10 years, decreased from age 10 to 15 but then increased again to reach adult levels. LDL-C levels were consistently and significantly higher in female children and those of Black ethnicity or with a higher body mass index.

In a discussion of their findings, the authors noted how LDL-C levels peaked between ages 9 and 11 and that these levels were comparable to those aged 18 years. This, the authors suggested, highlighted the importance of childhood lipid screening from as early as 9 years of age.

Citation
Zhang Y et al. Low-Density Lipoprotein Cholesterol Trajectories and Prevalence of High Low-Density Lipoprotein Cholesterol Consistent with Heterozygous Familial Hypercholesterolemia in US Children. JAMA Pediatr 2021

Omega-3 supplements reduce markers of inflammation in response to stress

27th April 2021

Supplementing with fish oils appears to offer some level of protection against cardiovascular disease but whether this effect arises through blunting the stress responsive system is unclear.

In a large, prospective study of nearly half a million individuals, higher intakes of fish intake were associated with a reduced all-cause mortality. One factor associated with biological ageing is the length of telomeres, which are strands of DNA at the ends of chromosomes and there is good evidence that telomere shortening is associated with increased mortality and how among individuals who consume higher amounts of omega-3 fatty acids, there is a reduced risk of telomere shortening. Moreover, increased physiological stress is a risk factor for many physical and mental health diseases and again, there is a suggestion that the pro-inflammatory response to psychological stress is attenuated to some extent by omega-3 fatty acids. Taken together, these results suggest that supplementing with omega-3 fatty acids may positively impact on markers of stress reactivity. This was the hypothesis considered by a team from the Institute for Behaviour Medicine Research, the Ohio State University College of Medicine, Ohio, US who examined a group of individual’s response to a social stress test. The team randomised participants into three groups who received either 2.5g/day, 1.25g/day of omega-3 or placebo for 4 months. At baseline, all participants were required to undergo the stress test which involved delivering a 5-minute speech without the use of aids or notes. Both saliva and blood samples were collected before the stress test and at 0.75, 1.25, 1.75 and 2 hours after and the test repeated at the end of the study. Parameters evaluated included cortisol, telomerase (an enzyme that maintains and restores telomeres) and several pro-inflammatory markers, interleukins 6, 10 and 12 as well as tumour necrosis factor (TNF). Participants were also required to score their anxiety levels before and after the test.

Findings
A total of 138 individuals were recruited (63% female) with a mean age of 51.1 years and with 72% of white ethnicity. Among those taking 2.5g/day of omega-3, their salvia cortisol levels were 19% lower throughout the final stress test compared to those given placebo (p = 0.01) although this difference was not significant for the 1.25g/day group. Similarly, the high dose supplement group had a 33% lower interleukin-6 level compared to placebo (p = 0.007). However, there were no differences with the other interleukin levels or of TNF. While telomerase levels remained unchanged in both supplement groups, levels dropped between 45 and 120 minutes after the stress test by 24%.

The authors commented on how 2.5g/day of omega-3 fatty acid supplementation blocked the stress-related decline in telomerase level as well as reducing levels of both cortisol and the pro-inflammatory interleukin-6 in a dose dependent manner. They suggested that omega-3 supplements had a unique stress-buffering effect on biomarkers of cellular ageing, concluding that while their data were preliminary, if replicated, it could limit the impact of repeated stress.

Citation
Madison AA et al. Omega-3 supplementation and stress reactivity of cellular ageing biomarkers: an ancillary sub-study of a randomised, controlled trial in midlife adults. Mol Psychiatry 2021.