**1. Introduction**

Cardiovascular diseases (CVD) are a group of disorders of the heart and blood vessels, including coronary heart disease, cerebrovascular disease, rheumatic heart disease and other conditions. The global CVD mortality increased 12.5% from 2005 to 2015. 17.9 million people died of CVD in 2015 [1]. In addition to drug treatment, the potential role of dietary components hasreceived increased attention. Previous studies have shown the effectiveness of healthy dietary patterns and components for the prevention of CVD and other diseases [2–4]. Fish is rich in various nutrients (e.g., protein, vitamin D and polyunsaturated fatty acids) and may have a beneficial role in preventing CVD events [5,6].

Marine n-3 polyunsaturated fatty acids (n-3 PUFA)—including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)—mainly exist in fatty fish. A high consumption of n-3 PUFA from fatty fish led to an increase in highdensity lipoprotein and a decrease in inflammation factors [7,8]. Besides, n-3 PUFA may improve heart rate and blood pressure through improving left ventricular diastolic filling or augmenting vagal tone [9].

Previous epidemiological studies have investigated the association of fish consumption with CVD mortality risk [10,11]. A recent meta-analysis of prospective observational studies revealed a negative association between fish intake and CVD mortality risk [12]. In recent years, another 11 prospective cohort studies investigated the association between

**Citation:** Jiang, L.; Wang, J.; Xiong, K.; Xu, L.; Zhang, B.; Ma, A. Intake of Fish and Marine n-3 Polyunsaturated Fatty Acids and Risk of Cardiovascular Disease Mortality: A Meta-Analysis of Prospective Cohort Studies. *Nutrients* **2021**, *13*, 2342. https://doi.org/10.3390/nu13072342

Academic Editor: Hayato Tada

Received: 21 May 2021 Accepted: 4 July 2021 Published: 9 July 2021

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fish intake and CVD mortality risk, but the findings were inconsistent [13–16]. The EPIC-Netherlands cohort study suggested that fish was not associated with the risk of CVD mortality [17]. In contrast, the NIH-AARP Diet and Health Study found that fish had a protective effect on CVD mortality risk [18]. To our knowledge, there has been no metaanalysis of prospective observational studies for investigating the association of marine n-3 PUFA consumption with CVD mortality risk. Therefore, we conducted this meta-analysis to comprehensively investigate the associations between fish, marine n-3 PUFA intake and CVD mortality risk. Furthermore, dose-response analyses were conducted to quantify the associations.

#### **2. Materials and Methods**
