Consumption of fruit and vegetables has been shown to lower the risk of CVD [28
]. Fruit and vegetables have a unique nutrient profile in that in general, they are rich in fiber, potassium, polyphenols, and other minerals like magnesium, various vitamins, and usually have low energy densities, and fat content. Flavonoids are a chemically related class of various plant derived bioactive molecules including flavanols, flavonols, flavones, isoflavones, flavanones, and anthocyanins. Flavonoids have been suggested to impart a protective role against cardiovascular events.
In the Zutphen Elderly Study, dietary intake of flavonoids was assessed by dietary history of 805 men aged 65–84 years [30
] and major sources of flavonoid intake were tea (61%), onions (13%) and apples (10%). As compared to the lowest tertile of flavonoid intake, those in the highest tertile had a 68% reduced risk of CHD mortality (multivariable adjusted RR= 0.32, 95% CI 0.15–0.71, p value for trend 0.003). As compared to the lowest tertile (0–250 ml per day) of tea consumption, the highest tertile (>500 ml per day) was associated with a statistically significant 55% reduced risk of CHD mortality. Similarly, highest tertile (≥ 110 g per day) of apple consumption was associated with 49% reduced CHD mortality. In 34,492 postmenopausal women of the Iowa Women’s Health Study, total flavonoid intake was associated with a decreased risk of CHD mortality after adjusting for age and energy intake (p value for trend 0.04)[31
]. Although this association was attenuated after multivariate adjustment, a decreased risk was seen in each quintile of flavonoids compared with the lowest. Relative risks (95% CI) of CHD death from lowest to highest intake quintile were 1.0, 0.67 (0.49–0.92), 0.56 (0.39–0.79), 0.86 (0.63–1.18), and 0.62 (0.44–0.87), respectively. Consumption of broccoli was associated with a statistically significant 48% reduction in CHD mortality in the highest quintile of intake (RR=0.52, 95% CI 0.37–0.74). Other studies documenting an inverse association between dietary flavonoids and CHD are the Rotterdam Study[32
], Finnish mobile clinic health examination survey[33
], Alpha-Tocopherol, Beta Carotene Cancer Prevention Study[34
], and the Zutphen Elderly Study for catechins [35
On the other hand, the Health Professionals Follow-up Study failed to find any significant protective effects of total flavonoid intake on the risk of nonfatal MI(multivariable adjusted RR=1.08; 95% CI 0.81–1.43)[36
]. A statistically non-significant 36% risk reduction in CHD death was seen in subjects who had prevalent CHD (RR=0.64, 95% CI 0.39–1.04). Similarly, in the 38,445 female participants of the Women’s Health Study, flavonoid intake did not protect against CVD[37
]. This lack of protection was observed across different type of flavonoids. When individual foods were analyzed, apple, tea and broccoli, but not onions were associated with statistically non significant reduced risk of CVD. Insufficient power and lack of comprehensive control for potential confounding factors in some analyses were acknowledged by the authors. The Caerphilly Study suggested a positive association between flavonol intake and CHD mortality[38
]. As compared to the lowest quintile of total flavonol consumption, the RR of CHD mortality in the highest quintile was 1.6 (95% CI 0.9– 2.9, p value = 0.2). Men with the highest consumption of tea (> 1.2 L, or > 8 cups/d) had an RR of 2.3 (95% CI 1.0–5.1, p value for trend 0.031) of dying from CHD in the follow-up period compared with men consuming < 300 mL/d (< 2 cups/d). Almost all men used milk in their tea, and it is possible that milk may attenuate antioxidant capacity of tea.
Polyphenol- rich foods such as cocoa have shown to have cardiovascular benefits. Decreased CHD mortality from cocoa consumption were demonstrated in the Zutphen Elderly Study [39
]. As compared to the lowest tertile of cocoa consumption, the mean systolic blood pressure in the highest tertile of cocoa intake was 3.7 mm Hg lower (95% CI −7.1 to −0.3 mmHg, p value for trend 0.03) and the mean diastolic blood pressure was 2.1 mm Hg lower (95% CI −4.0 to −0.2 mm Hg, p value for trend 0.03). As compared to the lowest tertile of cocoa intake, the adjusted RR of cardiovascular death in the highest tertile was 0.50 (95% CI 0.32–0.78, p for trend 0.004) and the RR of all-cause mortality was 0.53 (95% CI 0.39–0.72, p for trend <0.001). In a cross-sectional analysis of 2,217 participants of the Family Heart Study, an inverse association between frequency of chocolate consumption and prevalent coronary artery calcification (CAC) scores was demonstrated [40
]. As compared to the study participants who reported no chocolate consumption, the multivariable adjusted odds ratios (95% CI) for CAC for those reporting chocolate consumption of 1–3 times per month, once per week, and 2 or more times per week were 0.95 (0.66–1.36), 0.79 (0.54–1.15), and 0.69 (0.48–0.99) respectively (p for linear trend 0.029). Exclusion of subjects with known CHD or diabetes mellitus did not significantly change the odds ratio estimates but did modestly decrease the overall significance (p value = 0.07). In another paper, cross-sectional data from the Family Heart Study also suggested an inverse association between chocolate consumption and prevalent CHD[41
]. Compared to subjects who did not report any chocolate intake, odds ratios (95% CI) for CHD were 1.01 (0.76–1.37), 0.74 (0.56–0.98), and 0.43 (0.28–0.67) for subjects consuming 1–3 times/month, 1–4 times/week, and 5+ times/week, respectively (p value for trend <0.0001).
The observed protective effects of flavonoid intake on CHD have been attributed to various mechanisms. Flavonoids have been shown to induce an acute and sustained increase in endothelium- dependent vasodilatation in people with cardiovascular risk factors [42
], as well as those with established CHD [45
]. Ingestion of dark chocolate has been shown to induce flow- mediated dilation of brachial artery, an effect that has been shown to last for as long as 8 hours[43
]. An increase in circulating plasma nitric oxide storage forms following ingestion of various dietary flavonoids has been suggested [49
]. These molecules have intrinsic vasodilator activity. Besides, reduction in blood pressure[50
], total and low density lipoprotein cholesterol[51
], and inhibition of platelet aggregation [52
] seen with dietary flavonoid use may account for the observed benefits.