Fresh fruit consumption and early markers of carotid atherosclerosis

According to the 2015 Report on Cardiovascular Disease in China, there are approximately 230 million Chinese with CVD and 3.5 million annual cardiovascular deaths [1]. The general perception that non-communicable diseases are exclusively western diseases or diseases of the wealthy is no longer accurate as low and middle-income countries, such as China, account for approximately 80% of the CVD burden worldwide [2].

In 2016, a large prospective study, using the China Kadoorie Biobank (CKB) data, investigated the association of fresh fruit consumption with the risks of major cardiovascular disease in China [3]. The CKB recruited ~0.5 million people from 10 diverse localities and had over 3.2 million person-years of follow up. The study reported adjusted hazard ratios for daily consumers of fresh fruit vs those who never or rarely consumed fresh fruit was 0.60 (95% CI: 0.54-0.67) for cardiovascular death, and 0.66 (95% CI: 0.58-0.75), 0.75 (95% CI: 0.72-0.79), and 0.64 (95% CI: 0.56-0.74) for incident major coronary event, ischemic stroke, and haemorrhagic stroke, respectively. Based on these results, we hypothesised that increased fresh fruit intake may be protective against atherosclerosis in the Chinese population.

My MSc project examined cross-sectional associations between fresh fruit intake and three markers of atherosclerosis using data from the 2nd resurvey of the CKB from 2013-2014 (N=25,242 adults). The markers used to detect atherosclerosis included increased carotid intima media thickness (CIMT), plaque prevalence, and carotid plaque burden. CIMT reflects hypertrophy of both the intima and media layers of the carotid artery wall. Presence of carotid plaque was defined as any focal thickening >1.5 mm of the carotid artery intima layer. Lastly, carotid plaque burden is a composite measure that incorporates both the number and size of carotid plaques [4].

Our results indicated that in men, there was a significant inverse association between quintiles of fresh fruit intake (g/day) and both carotid plaque burden and plaque prevalence (Fig 1, 2). A 100 g increase in fresh fruit intake per day was associated with a 0.035 mm (95% CI 0.01, 0.06) reduction in plaque burden and a 5% decrease in the odds of plaque prevalence (OR = 0.95, 95% CI: 0.91-0.99). No associations were found for women and associations with CIMT for both sexes were non-significant (Fig 1).

Figure 1: The association of quintiles of fresh fruit intake and mean CIMT (left-panel) and mean carotid plaque burden (right-panel) by sex. Linear regression models are adjusted for the interaction between age and region, ever smoker, ever drinker, physical activity (MET-h/d), household income, education, red meat (g/day), fish (g/day), other staple foods (g/day), refined grain (g/day), and fresh vegetables (g/day). Error bars indicate 95% confidence interval (CI).

Figure 2: The association between quintiles of fresh fruit intake and plaque prevalence by sex. Logistic regression models were adjusted for the interaction between age and region, ever smoker, ever drinker, physical activity (MET-h/d), household income, education, red meat (g/day), fish (g/day), other staple foods (g/day), refined grain (g/day), and fresh vegetables (g/day). All floating absolute risks (FARs) were derived from odds ratios relative to the lowest quintile of fresh fruit intake and represent group specific risks. Error bars indicate 95% confidence interval (CI).

This was the first study to examine the relationship between fresh fruit consumption, CIMT and carotid plaque in China on a large scale. The study was also able to limit the effects of reverse causality by utilising health records to exclude participants who had experienced a prior clinical CVD event. However, there are also several limitations to consider. First, the food frequency questionnaire (FFQ) used to measure fruit consumption in the CKB provides a somewhat crude assessment of fresh fruit intake. Second, FFQs are subject to bias. Recall bias occurs when participants are not accurately able to recall their frequency of fruit consumption over the past year. Additionally, social desirability bias may occur as FFQs tends to overestimate total fruit intake. Third, the associations found may be subject to residual confounding as factors such as socioeconomic status and total energy intake are challenging to adjust for.

I believe that appropriate management, using counselling and medicine, for patients with atherosclerosis is the most cost-effective method to reduce the burden of CVD. Hence, if more research reliably supports the claim that high fresh fruit intake decelerates the progression of atherosclerosis in men, this finding could prove to be very useful in dietary counselling for patients who are at high cardiovascular risk.

Jayanth (Jay) Krishnan completed his MSc dissertation at the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) under the guidance of Huaidong Du, Jennifer Carter, and Matthew Arnold. Prior to arriving at Oxford, Jay received a BS in Molecular, Cellular, and Developmental Biology from Yale College. He hopes to pursue a career at the nexus of disease informatics and public policy.

References

[1] Chen W, Gao RL, Liu LS et al. China cardiovascular diseases report 2015: a summary. J Geriatric Cardiology.  2017 Jan; 14(1): 1–10.

[2] Yusuf S, Haken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case control study. Lancet 2004; 364:937-52.

[3] Du H, Li L, Bennett D et al. (2016) Fresh fruit consumption and major cardiovascular disease in China. N Engl J Med 374: 1332–1343. pmid:27050205.

[4] Clarke R, Du H, Kurmi O et al. Burden of carotid artery atherosclerosis in Chinese adults: Implications for future risk of cardiovascular disease. Eur J Prev Cardol. 2017. 24: 647-656