To explore potential reasons for the gender difference in the impact of the intervention, we compared men and women on baseline BMI and CRP levels. There were no differences in BMI between women and men (31.9 ± 9.7 kg/m2 vs 30.7 ± 6.7 kg/m2, respectively; P = .638). There were differences in CRP levels between women and men (5.69 ± 3.5 mg/L vs 2.86 ± 2.62 mg/L, respectively; P = .01).
Plasma lycopene levels increased significantly in the intervention group compared with the control group (P = .02). Plasma lycopene levels changed similarly between men and women in the intervention group (P = .37). There was no significant group × time interaction on sodium intake (P = .237; Table 3).
This is the first study in which an intervention of a lycopene-rich food source has been tested in a sample of patients with HF. To date, there have been 2 other studies in which the role of antioxidants in patients with HF has been studied. In both studies, there was a positive association between plasma lycopene levels and HF; both of these studies were observational.33,34
In our study, we found a differential effect of gender in the effect of the intervention on CRP levels. In women, but not in men, the intervention resulted in a significant decrease in CRP levels across time.
There are 3 potential explanations for our finding of a gender effect in the intervention. The possibilities include (1) greater compliance to the intervention in women than in men, (2) the effect of BMI and adiposity, and (3) the higher baseline CRP levels seen in women. With regard to the first potential explanation, there is published evidence that women are more adherent to prescribed HF regimens than men are.35 There was, however, no evidence in our sample that women were more compliant to the intervention than men were. Lycopene levels increased significantly in both genders in the intervention group over time, while remaining unchanged in both genders in the control group.
With regard to the second potential explanation for our findings, adipose tissue produces inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which contribute to atherosclerosis. Interleukin-6 enhances liver production of CRP. Levels of inflammatory markers in obese persons (BMI ≥30 kg/m2) are considered independent predictors of CVD. Abdominal adiposity has been associated with risk of CVD in women.36,37 Higher waist-to-hip ratio (WHR) and greater waist circumference have been found to be independently associated with a significantly increased age-adjusted risk of CVD and HF.36,38,39 In the Nurses’ Health Study, women with a WHR of 0.88 or higher had a relative risk of 3.25 (95% confidence interval, 1.78–5.95) for CVD compared with women with a WHR of less than 0.72.36 There was no gender difference in BMI level in our sample of patients. However, we did not measure abdominal adiposity. This additional measurement may have shed additional light onto our findings.
With regard to the third potential explanation for our findings, women may have higher baseline levels of CRP than men do.40 For example, female participants enrolled in the Women’s Health Study had a median CRP level of 0.42 mg/dL compared with 0.28 mg/dL in men.41 In our sample, women had significantly higher baseline CRP levels than men did. Often, the effect of a variety of interventions (eg, cardiac rehabilitation, weight loss, intake of healthy foods) is greater in those in whom the outcome of interest is most negatively affected. That is, those who have the most to gain (or lose) often show the largest effect of an intervention, at least initially.42–47 Thus, it is plausible that the substantially higher levels of CRP seen in the women in our study allowed the intervention to better exert its effect.
Our data also indicate that increased consumption of lycopene-containing food products results in increased plasma levels of lycopene. These data support previous studies where increased dietary intake of lycopene is reflected in increased circulating lycopene levels in plasma.53–55 Compliance to the V8 juice intervention was observed in both women and men in our study.
Processed foods containing high levels of lycopene also contain high levels of sodium. Approximately 80% of the sodium in the average American diet comes from processed foods. Dietary sodium indiscretion is considered to be a precipitant in more than 20% of patients hospitalized for decompensated HF, and high sodium intake is an independent risk factor for HF exacerbation.56–58 Data from an earlier investigation of ours suggest that foods containing high levels of lycopene may be beneficial regardless of its sodium content.59 The findings of the current study did not indicate a significant increase in sodium levels after the intervention.
An important challenge in translating these findings into clinical treatment strategies relates to the fact that most clinical studies have been designed on top of established pharmacological therapy, whereas most experimental studies test novel interventions without concomitant drug regimens such as angiotensin-converting enzyme inhibitors or β-blockers. Our study tested a randomized intervention on top of evidence-based drug regimens for patients with HF and found an impact of a dietary intervention. We cannot attribute the intervention effect solely to lycopene, as V8 juice does contain a variety of antioxidants and vitamins. However, V8 juice does contain a large amount of lycopene, nearly 4 times the reported average amount found in the daily intake for individuals in the United States.
With regard to the feasibility of this study of a dietary intervention, we found that patients with HF were able to adhere to the intervention, as evidenced by a compliance rate of 100%. The V8 juice costs less than $1.00 per serving and is readily available in most urban and rural grocery stores. The patients did not report any ill effects from drinking the lycopene product for 30 days. This intervention was easily implemented by a sample of patients with difficult self-care regimens.
In addition to establishing feasibility, the study has strength in the 2-group randomization of participants. Second, we were able to obtain valuable detailed nutritional information from the participants via randomly collected dietary 24-hour recalls at multiple time points. There are several limitations to this study. Because of the small sample size, it is difficult to generalize to the entire population of people with HF. Additional biomarkers of inflammation, such as inflammatory cytokines, could be measured in conjunction with CRP to further elucidate the impact of inflammation in HF. The gender differential we found warrants further investigation as well.
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