Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis

Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis

International Journal of Cardiology 202 (2016) 967–974 Contents lists available at ScienceDirect International Journal of Cardiology journal homepag...

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International Journal of Cardiology 202 (2016) 967–974

Contents lists available at ScienceDirect

International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis Jun Pang a,e, Zheng Zhang a,⁎, Tong-zhang Zheng b,⁎⁎, Bryan A. Bassig c, Chen Mao e, Xingbin Liu e, Yong Zhu c, Kunchong Shi d, Junbo Ge f, Yue-jin Yang g, Dejia-Huang e, Ming Bai a, Yu Peng a a

Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, China Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA Yale School of Public Health, Yale University, USA d Brown-China Center for Environmental Health Sciences, Brown School of Public Health, Providence, USA e Department of Cardiology, Huaxi Hospital of Sichuan University, Chengdu, China f Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China g Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Beijing, China b c

a r t i c l e

i n f o

Article history: Received 25 November 2014 Received in revised form 16 December 2014 Accepted 31 December 2014 Available online 4 January 2015 Keywords: Green tea Cardiovascular disease Ischemic related disease Meta-analysis

a b s t r a c t Background: The effects of green tea intake on risk of cardiovascular disease (CVD) have not been well-defined. The aim of this meta-analysis was to evaluate the association between green tea consumption, CVD, and ischemic related diseases. Methods: All observational studies and randomized trials that were published through October 2014 and that examined the association between green tea consumption and risk of cardiovascular and ischemic related diseases as the primary outcome were included in this meta-analysis. The quality of the included studies was evaluated according to the Cochrane Handbook 5.0.2 quality evaluation criteria. Results: A total of 9 studies including 259,267 individuals were included in the meta-analysis. The results showed that those who didn't consume green tea had higher risks of CVD (OR = 1.19, 95% CI: 1.09–1.29), intracerebral hemorrhage (OR = 1.24, 95% CI: 1.03–1.49), and cerebral infarction (OR = 1.15, 95% CI: 1.01–1.30) compared to b 1 cup green tea per day. Those who drank 1–3 cups of green tea per day had a reduced risk of myocardial infarction (OR = 0.81, 95% CI: 0.67–0.98) and stroke (OR = 0.64, 95% CI: 0.47–0.86) compared to those who drank b 1 cup/day. Similarly, those who drank ≥4 cups/day had a reduced risk of myocardial infarction compared to those who drank b1 cup/day (OR = 0.68, 95% CI: 0.56–0.84). Those who consumed ≥10 cups/day of green tea were also shown to have lower LDL compared to the b3 cups/day group (MD = −0.90, 95% CI: −0.95 to −0.85). Conclusions: Our meta-analysis provides evidence that consumption of green tea is associated with favorable outcomes with respect to risk of cardiovascular and ischemic related diseases. © 2015 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Cardiovascular diseases (CVD), which include cerebrovascular disease, coronary heart disease, and peripheral arterial diseases, are major contributors to the global disease burden. The overall incidence rate of CVD was 235.5 per 100,000 in 2010 in the United States [1]. Previous research has provided evidence that several dietary factors are related to the risk of CVD, such as diets high in sodium and fat, which have been associated with higher risk of CVD [1]. It

⁎ Correspondence to: Z. Zhang, Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou 730000, China. ⁎⁎ Correspondence to: T.Z. Zheng, Department of Epidemiology, School of Public Health, Brown University, Providence, RI, 02912, USA. E-mail addresses: [email protected] (Z. Zhang), [email protected] (T. Zheng).

http://dx.doi.org/10.1016/j.ijcard.2014.12.176 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.

is of interest to identify associations with other dietary factors that may reduce the risk of CVD. Green tea is a common beverage that has been demonstrated to be an antioxidant and that has also been associated with antiatherosclerosis in clinical trials [2,3]. Polyphenols, which are considered the effective ingredient in tea, have important roles in preventing coronary artery disease [3]. There have been several clinical trials evaluating the association between green tea consumption and coronary artery disease and ischemic related diseases [4–6]. The main results have showed that drinking green tea could be beneficial in CVD; however, the associations between clinical outcomes and green tea consumption are inconsistent. In order to review and synthesize the current evidence for associations between green tea consumption and risk of coronary artery disease and ischemic related diseases, we conducted a meta-analysis of all available studies that were published by October 2014.

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Fig. 1. Flow chart of article screening and selection process. 2. Materials and methods

2.2. Data extraction and quality assessment

2.1. Search strategy and study selection

Two evaluators performed literature searches independently. When there were disagreements about whether to include studies or about the quality assessment of identified studies, the two evaluators met to discuss and resolve the discrepancies. The primary endpoints that were evaluated in the meta-analysis included risk of CVD, all cause death, cardiovascular death, and myocardial infarction. Secondary endpoints included hypertension, stroke, cerebral infarction, intracerebral hemorrhage, hyperlipidemia, diabetes, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum total cholesterol, and low density lipoprotein (LDL). In order to reduce the influence of confounding factors on the associations, we excluded papers in which the baseline characteristics of subjects were incomparable. We selected studies with similar baseline characteristics across groups such as similar concomitant medications, concomitant diseases, age, and gender in order to make sure the two groups were comparable. Subgroup analyses were carried out according to different amounts of tea consumption in order to reduce the heterogeneity that existed among the different studies. The green tea consumption subgroups were divided as follows: none, b1 cup/day, 1–3 cups/day, and ≥4 cups/day.

A flow diagram describing the process we used to identify and include relevant studies is shown in Fig. 1. We searched the following electronic databases for relevant studies: PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library. The following search terms were used: green tea, cardiovascular disease, coronary heart disease, cerebral infarction, intracerebral hemorrhage, and ischemic related disease. We also reviewed the references in the included studies in order to identify additional relevant articles. In addition, manual searches of conference abstracts were also carried out to identify studies that met the inclusion criteria. Articles published in these databases through October 2014 were included in the study. All trials that examined the association between green tea consumption and risk of cardiovascular disease and ischemic related diseases as the primary outcome were included in the meta-analysis. Cardiovascular diseases were diagnosed based on the criteria defined by the American Heart Association. Studies were excluded if they were review articles, animal experiments, molecular biological experiments, or if there was significant heterogeneity in the baseline information of the study populations with respect to factors such as age, gender, and primary diseases.

2.3. Data synthesis and meta-analysis Data analyses were carried out following the Cochrane handbook. The odds ratios (ORs) and corresponding 95% confidence intervals (CI) for each endpoint were

Table 1 Basic characteristics of included studies. Study

Study type

Total subjects

Age (years)

Female

Yoshihiro Kokubo—2013

Cohort study

100,938

45–74

28.0%

Etsuji Suzuki—2009

14,001

65–84

49.3%

76,979 40,530

40–79 40–79

55.4% 53.0%

51

45.3 ± 13.2

63.5%

Shizuka Sasazuki—2000

Prospective cohort study Prospective Prospective cohort study Randomized controlled trial (RCT) Prospective

512

58.5 ± 1.0

41.0%

Tanabe N—2008 stroke

Prospective

6358

40–89

67.0%

Yasutake Tomata—2012

Prospective

13,988

73.9 ± 6.1

46.8%

Yoshikazu Sato—1989

Prospective

5910

Yohei Mineharu—2009 Shinichi Kuriyama—2006 Toshimasa Sone—2001

≥40

100.0%

Outcome indicators

Follow-up

Years range

Cardiovascular disease, stroke, cerebral infarction, intracerebral hemorrhage, coronary heart disease All-cause mortality, cardiovascular disease mortality

13 years

1995–2007

6 years

1999–2006

CVD, CHD Cardiovascular disease mortality, coronary heart disease, stroke, cerebral infarction, cerebral hemorrhage LDL

2 years 11 years

1988–1990 1995–2005

9 weeks

Hypertension, hyperlipidemia, myocardial infarction, diabetes mellitus, cardiovascular disease Systolic blood pressure, diastolic blood pressure, serum total cholesterol Incident functional disability, stroke, myocardial infarction, dyslipidemia, diabetes Stroke, hypertension

1 year

June 2007– September 2007 1996–1997

6 years

1998–2003

3 years

2006–2009

4 years

1985–1989

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Table 2 The association between green tea consumption and cardiovascular diseases and ischemic related diseases. Groups

Cardiovascular disease

All cause death Cardiovascular death Myocardial infarction Hypertension

Stroke

Cerebral infarction

Intracerebral hemorrhage

Diabetes Serum total cholesterol

CVD events/total population

None vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day None vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day None vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day None vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day None vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day 1–3 cups/day vs b1 cup/day ≥4 cups/day vs b1 cup/day

Others

b1 cup/day

1070/17,606 878/17,578 1236/23,520 2162/20,173 2100/21,135 368/17,192 263/12,186 396/7271 250/4824 125/442 4716/14,024 3641/11,093 1616/21,124 1181/35,808 1094/54,333 471/17,606 493/37,491 610/37,897 222/17,606 230/34,618 315/35,433 1048/10,144 740/7188 2873 2364

1242/24,090 1268/24,177 1268/24,177 1171/11,023 1171/11,023 261/10,702 261/10,702 166/2405 166/2405 309/1283 1495/4658 1495/4658 1328/28,788 1448/32,076 1448/32,076 563/24,090 643/35,762 643/35,762 246/24,090 280/34,792 280/34,792 369/3375 369/3375 970 970

abstracted from the included studies for the meta-analysis. We also used the reported mean differences (MD) and 95% CI for analyses of endpoints where applicable. Statistical heterogeneity among studies was evaluated through the chi-square test and the I2. An I2 N 50% was considered to indicate noteworthy heterogeneity and in these cases a random effects model was used for the analysis. P b 0.05 was considered statistically significant in all analyses. We also evaluated the publication bias of the included studies.

P value

Z value

OR/MD (95% CI)

b0.0001 0.10 0.40 0.37 0.37 0.10 0.16 0.03 0.0003 0.08 0.06 0.05 0.12 0.003 0.09 0.03 0.17 0.18 0.02 0.78 0.10 0.29 0.46 0.24 0.57

4.06 1.66 0.84 0.90 0.89 1.63 1.42 2.21 3.62 1.75 1.89 1.92 1.54 2.97 1.68 2.19 1.36 1.34 2.29 0.28 1.63 1.05 0.73 1.17 0.56

1.19[1.09,1.29] 0.93[0.85,1.01] 0.79[0.45,1.37] 0.79[0.47,1.32] 0.66[0.26,1.65] 0.88[0.75,1.03] 0.88[0.74,1.05] 0.81[0.67,0.98] 0.68[0.56,0.84] 1.24[0.97,1.59] 1.07[1.00,1.15] 1.20[1.00,1.45] 1.91[0.84,4.35] 0.64[0.47,0.86] 0.28[0.06,1.24] 1.15[1.01,1.30] 0.81[0.60,1.10] 0.74[0.48,1.15] 1.24[1.03,1.49] 0.97[0.82,1.16] 1.14[0.97,1.34] 0.93[0.82,1.06] 0.95[0.83,1.09] 0.04[−0.03,0.11] −0.02[−0.09,0.05]

articles that did not meet our inclusion criteria. A total of 9 clinical trials covering 259,267 individuals [4–12] were included in the final metaanalysis (Fig. 1). The main characteristics of the included studies are described in Table 1.

3.2. Meta-analysis results 3. Results 3.1. Literature search and study characteristics A total of 728 articles were identified using the specified search terms. We eliminated 254 summaries, 242 non-clinical trials, and 91 repeated references (i.e. same article was identified in more than 1 database) after a preliminary review of the article titles and abstracts. Then, after reading the full-text of the articles, we eliminated 132

3.2.1. CVD Those who never consumed green tea had higher CVD risk compared to those who consumed b1 cup/day (OR = 1.19, 95% CI: 1.09– 1.29). The risk of CVD was not statistically different, however, between the 1–3 cups/day and b 1 cup/day groups (OR = 0.93, 95% CI = 0.85– 1.01). Further, the risk of CVD was not statistically different between the ≥4 cups/day and the b1 cup/day groups (OR = 0.79, 95% CI: 0.45– 1.37) (Table 2, Fig. 2).

Fig. 2. The association between green tea consumption and cardiovascular disease.

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Fig. 3. The association between green tea consumption and all cause death.

3.2.2. All cause death The risk of all cause death was not statistically different between the 1–3 cups/day and b1 cup/day group (OR = 0.79, 95% CI: 0.47–1.32). All cause death risk was also not statistically different between the ≥4 cups/day and b1 cup/day groups (OR = 0.66, 95% CI: 0.26–1.65) (Table 2, Fig. 3). 3.2.3. Cardiovascular death risk The cardiovascular death risk was not statistically different between the 1–3 cups/day and b 1 cup/day groups (OR = 0.88, 95% CI: 0.75– 1.03). Compared to those who drank b1 cup/day, the OR for those who drank ≥ 4 cups/day was 0.88 (95% CI: 0.74–1.05), indicating no significant difference in cardiovascular death risk between these groups (Table 2, Fig. 4). 3.2.4. Myocardial infarction Those who drank 1–3 cups/day had a significantly reduced risk of myocardial infarction compared to those who drank b1 cup/day (OR = 0.81, 95% CI: 0.67–0.98). Those that consumed ≥ 4 cups/day also had a significantly reduced risk of myocardial infarction compared to those who drank b1 cup/day (OR = 0.68, 95% CI: 0.56–0.84) (Table 2, Fig. 5). 3.2.5. Hypertension The risk of hypertension was not statistically different between the non-green tea group and b1 cup/day group (OR = 1.24, 95% CI: 0.97– 1.59). Hypertension risk was also not statistically different between the 1–3 cups/day and b 1 cup/day groups (OR = 1.07, 95% CI: 1.00– 1.15), or between the ≥ 4 cups/day and b1 cup/day groups (OR = 1.20, 95% CI: 1.00–1.45) (Table 2, Fig. 6).

3.2.6. Stroke The risk of stroke was not statistically different between the nongreen tea group and b1 cup/day group (OR = 1.91, 95% CI: 0.84– 4.35). However, those who consumed 1–3 cups/day had reduced risk of stroke compared to those who drank b 1 cup/day (OR = 0.64, 95% CI: 0.47–0.86), although no significant difference was apparent for the ≥ 4 cups/day group compared to the b 1 cup/day group (OR = 0.28, 95% CI: 0.06–1.24) (Table 2, Fig. 7). 3.2.7. Cerebral infarction The non-green tea group had higher risk of cerebral infarction compared to the b 1 cup/day green tea group (OR = 1.15, 95% CI: 1.01–1.30). Cerebral infarction risk was not statistically different, however, between the 1–3 cups/day and b 1 cup/day groups (OR = 0.81, 95% CI: 0.60– 1.10), or between the ≥ 4 cups/day and b 1 cup/day groups (OR = 0.74, 95% CI: 0.48–1.15) (Table 2, Fig. 8). 3.2.8. Intracerebral hemorrhage The non-green tea group had higher risk of intracerebral hemorrhage compared to the b 1 cup per day green tea group (OR = 1.24, 95% CI: 1.03–1.49). The risk of intracerebral hemorrhage was not statistically different between the 1–3 cups/day and b1 cup/day groups (OR = 0.97, 95% CI: 0.82–1.16), or between the ≥ 4 cups/day and b1 cup/day groups (OR = 1.14, 95% CI: 0.97–1.34) (Table 2, Fig. 9). 3.2.9. Diabetes Diabetes risk was not statistically different between the 1–3 cups/day and b 1 cup/day group (OR = 0.93, 95% CI: 0.82–1.06). Diabetes risk was also not statistically different between the ≥4 cups/day and b1 cup/day groups (OR = 0.95, 95% CI: 0.83–1.09) (Table 2, Fig. 10).

Fig. 4. The association between green tea consumption and cardiovascular death.

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Fig. 5. The association between green tea consumption and myocardial infarction.

3.2.10. Serum total cholesterol The serum total cholesterol was not statistically different between the 1–3 cups/day and b1 cup/day group (MD = 0.04, 95% CI: − 0.03 to 0.11). Serum total cholesterol was also not statistically different between the b1 cup/day and ≥4 cups/day group (MD = −0.02, 95% CI: −0.09 to 0.05) (Table 2, Fig. 11). 3.2.11. Low density lipoprotein (LDL) LDL was not statistically different between the 4–9 cups/day and b 3 cups/day groups (MD = 0.00, 95% CI: −0.04 to 0.04). Those who drank ≥10 cups/day had lower LDL compared to those who drank b3 cups/day (MD = −0.90, 95% CI: −0.95 to −0.85) (Table 3, Fig. 12). 3.3. Publication bias There was no significant publication bias among the included studies in this meta-analysis. 4. Discussion Our meta-analysis, which included 9 studies and 259,267 individuals, showed that green tea consumption at varying consumption levels

was significantly associated with lower risks of CVD, myocardial infarction, stroke, intracerebral hemorrhage, and cerebral infarction risk, as well as lower LDL. The main effective components in green tea are flavonoids, which comprise 30–50% of solid green teas [13]. The common flavonoids are epicatechin, epicatechin gallate, epigallocatechin, and epigallocatechin gallate. Phytochemical analyses and animal studies of green tea have reported that tea flavonoids could have antioxidative and antiinflammatory properties and may keep the stability of the vascular endothelium [13,20–24]. Thus, green tea could have beneficial effects in preventing the pathogenesis of several diseases such as CVD and cancer [14,25–27]. In addition, green tea has roles in promoting lipid metabolism, so it could also reduce LDL levels, in turn reducing the risk of CVD and myocardial infarction. Moore RJ [15] also has reported that epigallocatechin-3-gallate in green tea may have a favorable impact on vascular function, which could also be a mechanism by which green tea plays roles in reducing the risk of CVD. At the same time, our results showed that green tea could reduce LDL. And several animal model experiments also found that green tea could be effective in reducing LDL. Cai Y et al. [16] observed the role that green tea extract played in the apoliprotein E knockout mice with atheroma formation. The results showed that the green tea extract

Fig. 6. The association between green tea consumption and hypertension.

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Fig. 7. The association between green tea consumption and stroke.

could reduce the oxidized low-density lipoprotein (LDL), slightly lowered LDL and very LDL cholesterol with significant difference. And some other experiments also found that green tea could also play roles in lowering cholesterol and triglyceride concentrations in rats with hyperlipidemia [17]. The mechanism is that green tea catechins could decrease the LDL receptor protein level in rats. Another two studies also reported that tea could reduce the triglyceride and cholesterol concentrations in mice [18,19]. Our study didn't show that there was significant association between green tea consumption and either all cause or cardiovascular death. Meanwhile, some other studies found an inverse association between green tea consumption and death. Suzuki Etsuji et al. [5] reported that the patients who consumed N7 cups of green tea a day had a 55%

lower risk of all cause mortality and a 75% lower risk of CVD mortality. Schinichi et al. [4] reported that the participants who consumed N 5 cups/green tea a day had 16% lower all cause death and 26% lower CVD death risk during 7–11 years of follow-up. However, the metaanalysis results didn't show a significant difference in all-cause mortality or CVD mortality between the b 1 cup and ≥4 cups/green tea a day groups. There were some limitations in our study. First, not all of the studies reported the outcomes in relation to non-green tea drinking. Just three studies reported the outcome conditions of the non-green tea group [4, 6,12] and the other six studies only reported associations for b 1 cup/day compared with 1–3 or ≥4 cups/day [5–7,9–11]. Second, one of the included studies [6] focused on the effects of green tea and coffee at the

Fig. 8. The association between green tea consumption and cerebral infarction.

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Fig. 9. The association between green tea consumption and intracerebral hemorrhage.

same time. It is possible that there existed metabolic interaction effects between tea and coffee in influencing risk of these outcomes. We conducted sensitivity analyses by removing this study and the results were similar. Third, there was heterogeneity between the studies given differences in baseline characteristics such as gender and disease

history. Although we used random effects model when there was significant heterogeneity, it could not completely eliminate the heterogeneity among the studies. In sum, this meta-analysis showed that green tea consumption was significantly associated with lower risk of CVD, stroke risk, cerebral

Fig. 10. The association between green tea consumption and diabetes.

Fig. 11. The association between green tea consumption and serum total cholesterol.

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Table 3 The association between green tea consumption and LDL. Groups

b3 cups/day vs 4–9 cups/day b3 cups/day vs ≥10 cups/day

LDL Others

b3 cups/day

651 303

376 376

P value

Z value

MD (95% CI)

1.00 b0.00001

0.00 32.49

0.00[−0.04, 0.04] −0.90[−0.95, −0.85]

Fig. 12. The association between green tea consumption and LDL.

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