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Association between fresh fruit intake and cardiovascular disease risk in patients with diabetes: A prospective cohort study

Year: 2024

Type: article

Abstract: To the Editor: Diabetes, which is a rapidly growing global health concern, is prevalent in 11.2% of adults in China.[1] People with diabetes usually limit fruit intake to maintain blood glucose concentrations. However, there has been limited research on the effect of the frequency of fresh fruit intake on the incidence of cardiovascular events and mortality in patients with diabetes. This gap in knowledge extends to understanding the optimal level of fruit consumption for cardiovascular risk reduction and its variability across patient subgroups and event subtypes. We used a prospective cohort design to investigate the association between the frequency of fresh fruit intake and the risk of cardiovascular events, including ischemic heart disease and stroke, in patients with diabetes. We also examined potential differences in this relationship across various subgroups of individuals with diabetes. This study was based on the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project, which was conducted in 13 counties and districts across 9 prefecture-level cities in Fujian Province from 2017 to 2021. The ChinaHEART project was approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences (No. 2014-574). All participants provided informed consent by signing an informed consent form. We included 8853 individuals with diabetes at baseline (defined by a fasting glucose ≥7.0 mmol/L, or a non-fasting glucose ≥11.1 mmol/L, or a self-reported history of diabetes), and excluded those with self-reported CVDs (n = 538), those with incomplete questionnaire information (n = 32), and those with less than one year of follow-up (n = 1046). A total of 7237 subjects were included in the analysis of the study [Supplementary Figure 1, https://links.lww.com/CM9/C236]. The project adopted a standardized technical protocol and questionnaire, which was previously published.[2] The research team received uniform training, and equipment, such as the Omron HBP-1300 blood pressure monitor (Omron Corporation, Kyoto, Japan), Cardiocheck PA rapid lipid testing device (CardioChek PA Analyzer; Polymer Technology Systems, Indianapolis, Indiana, USA), and Baijie PD-G001 glucometer (Suzhou Pu Chun Tang Biotechnology, Suzhou, China), which were routinely used. If the difference in systolic blood pressure (SBP) between two measurements was >10 mmHg, a third measurement was taken, and the average of the last two measurements was used. To confirm information on cardiovascular events and death among the study subjects, data were compared with the death monitoring data of Fujian Province, the acute cardiovascular and cerebrovascular event reporting system of Fujian Province, the hospitalization information of Fujian Provincial Health Insurance, and through regular follow-up visits. Patients were classified as having diabetes if their fasting blood glucose concentrations were ≥7.0 mmol/L, if they self-reported a diagnosis of diabetes from a secondary or higher level hospital, or if they self-reported receiving antidiabetic treatment within the past 2 weeks. Patients with a fasting blood glucose concentration <7.0 mmol/L were considered to have blood glucose control. Hypertension was defined as an average SBP ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, if patients self-reported a diagnosis of hypertension from a secondary or higher level hospital, or if patients self-reported receiving antihypertensive treatment within the past 2 weeks. Patients were classified as having dyslipidemia if their fasting total cholesterol (TC) concentrations were ≥6.2 mmol/L, and/or triglyceride (TG) concentrations were ≥2.3 mmol/L, and/or high-density lipoprotein cholesterol (HDL-C) concentrations were <1.0 mmol/L, and/or low-density lipoprotein cholesterol (LDL-C) concentrations were ≥4.1 mmol/L, if they self-reported a diagnosis of lipid abnormalities from a secondary or higher level hospital, or if they self-reported receiving lipid-lowering treatment within the past 2 weeks. A scoring system was used for fresh fruit intake. Fresh fruit intake less than once a month was assigned 0 points, 1–3 times a month was assigned 1 point (defined as low frequency), 1–3 times each week was assigned 2 points, 4–6 times each week was assigned 3 points (defined as moderate frequency), and daily intake was assigned 4 points (defined as high frequency). Cardiovascular events were classified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Ischemic heart disease included codes I20–I25, hemorrhagic stroke included codes I60–I61 and I69.0–I69.2, and ischemic stroke included codes I63, I69.3, I69.4, and I69.8. The data are shown using the median (Q1, Q3) for quantitative data and frequency for qualitative data. The Kruskal–Wallis rank-sum tests and χ2 tests were used to assess differences between these groups. We developed competing risk models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events associated with fruit intake. To examine nonlinear relationships, we used restricted cubic splines. Likelihood ratio tests were used to assess interactions between fresh fruit intake and factors, such as sex, age, residence, drinking, smoking, glucose-lowering treatment, hypertension, and dyslipidemia. This was followed by detailed subgroup analyses to examine potential variations in the effects of fruit intake between different patient groups. Data cleaning and analyses were conducted using R software (version 4.2.2, The R Foundation for Statistical Computing, Vienna, Austria, https://www.r-project.org/). A two-tailed significance level was set at α = 0.05. The study included 7237 patients with diabetes, with a median age of 62 (55–68) years. The median follow-up duration was 4.1 (2.6–4.8) years, during which 538 (7.4%) individuals experienced cardiovascular events. Specifically, there were 107 (1.5%) cases of ischemic heart disease, 38 (0.5%) cases of hemorrhagic stroke, and 393 (5.4%) cases of ischemic stroke [Supplementary Table 1, https://links.lww.com/CM9/C236]. The frequency of fresh fruit intake was negatively associated with the risk of cardiovascular events. A higher frequency of fruit intake was significantly associated with a lower cumulative incidence of cardiovascular events [Supplementary Figure 2, https://links.lww.com/CM9/C236]. After adjusting for possible confounders, moderate- and high-frequency fresh fruit intake reduced the risk of cardiovascular events by 29% (HR = 0.71, 95% CI: 0.58–0.86, P <0.001) and 41% (HR = 0.59, 95% CI: 0.46–0.76, P <0.001), respectively, relative to low-frequency fresh fruit intake. The adjusted models showed that moderate- and high-frequency fresh fruit intake reduced the risk of ischemic stroke by 36% (HR = 0.64, 95% CI: 0.52–0.80, P <0.001) and 49% (HR = 0.51, 95% CI: 0.38–0.69, P <0.001), respectively [Supplementary Table 2, https://links.lww.com/CM9/C236 and Table 1]. Table 1 - Association of fresh fruit intake with cardiovascular events in patients with diabetes. Models Frequency of intake for fresh fruit Cardiovascular events Ischemic heart disease Hemorrhagic stroke Ischemic stroke Model 1 Low 1 (reference) 1 (reference) 1 (reference) 1 (reference) Moderate 0.69 (0.57–0.84) 0.90 (0.58–1.41) 1.19 (0.54–2.62) 0.63 (0.51–0.79) High 0.70 (0.55–0.88) 1.02 (0.60–1.72) 1.38 (0.56–3.36) 0.59 (0.45–0.79) Model 2 Low 1 (reference) 1 (reference) 1 (reference) 1 (reference) Moderate 0.69 (0.57–0.84) 0.92 (0.59–1.44) 1.21 (0.55–2.65) 0.64 (0.51–0.79) High 0.67 (0.53–0.85) 0.99 (0.59–1.67) 1.36 (0.56–3.32) 0.57 (0.43–0.76) Model 3 Low 1 (reference) 1 (reference) 1 (reference) 1 (reference) Moderate 0.68 (0.56–0.82) 0.89 (0.57–1.40) 1.26 (0.56–2.82) 0.62 (0.50–0.78) High 0.56 (0.43–0.72) 0.68 (0.39–1.19) 2.01 (0.82–4.94) 0.49 (0.37–0.67) Model 4 Low 1 (reference) 1 (reference) 1 (reference) 1 (reference) Moderate 0.71 (0.58–0.86) 0.93 (0.60–1.45) 1.30 (0.58–2.93) 0.64 (0.52–0.80) High 0.59 (0.46–0.76) 0.74 (0.42–1.29) 2.04 (0.82–5.03) 0.51 (0.38–0.69) Data are presented as HR (95% CI). Model 1 used days as the time scale and categorized fruit intake frequency into three groups: low, moderate, and high. It analyzed their associations with cardiovascular events, ischemic heart disease, hemorrhagic stroke, and ischemic stroke. Model 2 was further adjusted for gender and age. Model 3 was additionally adjusted for residence, education level, household income, and occupation. Model 4 was further adjusted for current smoking, alcohol consumption, body mass index, glucose-lowering treatment, blood glucose control, hypertension, and lipid abnormalities. CI: Confidence interval: HR: Hazard ratio. Sensitivity analyses were separately conducted using competing risk models that excluded subjects with a cardiovascular event within 1 year, adjusted for intake of rice flour, omnivorous grains, vegetables, red meat as well as physical activity, and applied age-scaling, respectively. All models indicated that fresh fruit intake has a consistent protective effect against cardiovascular events [Supplementary Tables 3–5, https://links.lww.com/CM9/C236]. The dose–response relationship between the fresh fruit intake score and the risk of cardiovascular events showed a nonlinear downward trend in the risk of cardiovascular events as the score increased, with a similar trend in the risk of ischemic stroke [Supplementary Figure 3, https://links.lww.com/CM9/C236]. The strength of the association between the frequency of fresh fruit intake and cardiovascular disease varied in some population subgroups. The subgroup analysis showed that the protective effect of high-frequency fresh fruit intake on cardiovascular events was more significant in patients with diabetes who received glucose-lowering treatment (HR = 0.54, 95% CI: 0.40–0.74, P <0.001) than in those who did not receive glucose-lowering treatment (HR = 0.66, 95% CI: 0.43–1.03, P = 0.068, interaction P = 0.045). Similar differences in moderate intake were also observed in the subgroup analysis of patients with lipid abnormalities (no lipid abnormalities: HR = 0.56, 95% CI: 0.41–0.76, P <0.001 vs. lipid abnormalities: HR = 0.84, 95% CI: 0.65–1.08, P = 0.160, interaction P = 0.040). However, in female and older (≥60 years) patients, high-frequency intake increased the risk of hemorrhagic stroke (HR = 8.73, 95% CI: 1.63–46.87, P = 0.011; HR = 3.02, 95% CI: 1.07–8.55, P = 0.037, respectively) [Supplementary Table 2, https://links.lww.com/CM9/C236]. The findings from this prospective cohort study suggested that increasing fresh fruit intake had a protective effect on cardiovascular events in patients with diabetes, and this protective effect became more pronounced with a higher frequency of intake. In particular, ensuring daily fruit intake while receiving glucose-lowering treatment reduced the risk of cardiovascular events by 46%. Daily fruit intake also lowered the risk of cardiovascular events in patients with coexisting hypertension or lipid abnormalities to a level comparable to patients without these comorbidities. Fruit intake is believed to contribute to a reduction in cardiovascular mortality. Moreover, cross-sectional surveys of East Asian patients with diabetes in China and South Korea[3,4] have shown that increasing the frequency of fresh fruit intake contributes to improved blood glucose control, thereby reducing the risk of coronary heart disease and stroke. Taken together with previous findings, our findings provide further insight into cardiovascular events in specific subgroups. We found that fruit intake was associated with a reduced risk of ischemic stroke. Moreover, daily fruit intake in patients who were not receiving glucose-lowering treatment provided a protective effect against ischemic heart disease [Supplementary Table 1, https://links.lww.com/CM9/C236]. However, daily fruit intake may increase the risk of hemorrhagic stroke, especially in older individuals or women. We only collected information on the frequency of fresh fruit intake and did not analyze the effect of the quantity and types of fruit intake. However, dietary habits, which are self-reported information, are relatively simple questions more likely to obtain accurate answers. A survey conducted on Chinese women showed that the use of food frequency questionnaires had good validity, reproducibility, and a reasonable correlation with food intake quantities.[5] Although the median follow-up duration was 4.1 years in this study, we acknowledge that the number of reported cases of ischemic heart disease and hemorrhagic stroke might not be sufficient. Nonetheless, we used a combination of various monitoring and follow-up methods to minimize the possibility of underreporting of outcome events. While our model estimations were carefully adjusted for potential confounding factors and we observed differences between subgroups using a subgroup analysis, there still may have been residual confounding effects. Nevertheless, the sensitivity analysis confirmed the robustness of the statistical conclusions in this study. In addition, this study was conducted among diabetic patients in southeastern China. For regions with significant lifestyle differences from Fujian, extrapolating the conclusions requires more evidence. This study contributes important evidence supporting the notion that an increased frequency of fresh fruit intake reduces the risk of cardiovascular events in patients with diabetes. In the majority of patients with diabetes, ensuring daily consumption of fresh fruits is advisable. However, in patients in whom there is a tendency for bleeding, particularly in older or female patients with diabetes, controlling the intake frequency and carefully choosing appropriate fruit types may be prudent. Acknowledgments We appreciate all the staff from the 13 project counties in Fujian province for their work and support in providing the data for this study. Funding This work was supported by the Fujian Province Pilot Project (No. 2020Y0060), the Fujian Provincial Health Youth Project (No. 2020QNB017), and the Chinese Academy of Medical Sciences Innovation Fund for Medical Science (2021-I2M-1-011). Conflicts of interest None.

Source: Chinese Medical Journal

DOI: 10.1097/cm9.0000000000003402