Estimates and trends in death and disability from atrial fibrillation/atrial flutter due to high sodium intake, China, 1990 to 2019

Abstract

Objective

The effect of sodium intake on atrial fibrillation (AF)/atrial flutter (AFL), with respect to sex and age, has yet to be elucidated. This study aims to compare long-term trends in AF/AFL death and disability due to high sodium intake in China from 1990 to 2019.

Methods

We utilized data from the Global Burden of Disease study to assess the mortality and disability burden of AF/AFL attributable to high sodium intake (> 5 g/d) in China from 1990 to 2019. Overtime trends and average annual percentage change (AAPC) were analyzed with adjustments for age, sex, period, and cohorts.

Results

In 2019, the number of AF/AFL deaths and disability-adjusted life years attributable to high sodium intake were 4209.944 (95% UI: [1250.690-8718.238]) and 235484.586 (95% UI: [89136.783-428566.694]), with males comprising 44.81% and 51.95% of cases, respectively. The age-standardized mortality rates (ASMRs) and age-standardized disability rates (ASDRs) of AF/AFL attributable to high sodium intake exhibited downward trends from 1990 to 2019 in China. The AAPC was − 0.221(95% CI: -0.321–0.121)and − 0.631(95% CI: -0.816–0.446) for AF/AFL, respectively. An upward trend was observed in ASMRs for AF and AFL, attributable to high sodium intake due to high salt intake at ages 30–34, 35–39, and 40–44. With an increase in age, the AAPC for ASMRs increased correspondingly, and the AAPC for ASDRs exhibited a decreasing trend.

Conclusions

Our findings provide strong evidence that high sodium levels in China significantly affect standard ASMRs and ASDRs for AF and AFL. Notably, different patterns of change are identified across various age groups, emphasizing the pronounced effect of salt reduction on AF and AFL.

Introduction

Atrial fibrillation (AF)/Atrial flutter (AFL) is identified as the most common persistent arrhythmia globally, along with stroke, heart failure, sudden death, and cardiovascular disease. These adverse events lead to high healthcare costs and constitute a significant public health burden [1]. The occurrence of AF/AFL is complex, and the primary risk factors include high blood pressure, smoking, alcohol consumption, high sodium intake, and obesity, among others. Sociodemographic factors (e.g., population, age, and ethnicity) and socioeconomic factors (e.g., income, education, and healthcare resources) also significantly contribute to the AF/AFL burden. Meanwhile, high blood pressure is the most crucial factor leading to atrial fibrillation [2]. In the 2019 Global, the incidence of new AF/AFL cases was approximately 4.720 million, with a prevalence of 59.695 million. Extrapolation from the Nordpred age–period–cohort model suggests that in the absence of effective interventions, the AF/ AFL total incidence in males is predicted to reach 16.08 million, with a total of 1.01 million deaths. For females, the total incidence is projected to be 16.85 million, with a total of 1.49 million deaths between 2030 and 2034 [3]. While the age-standardized AF/AFL death rate has declined by 2.53% over the past few decades, the absolute number of disability-adjusted life years (DALYs) due to AF/AFL has increased from 1990 to 2019, reaching 5.97 million people worldwide. In 2019 in China, the number of cases due to AF/AFL was about 60,000, and the number of people with disabilities was 0.4 million [4].

In the 2019 Global, 4.4 million deaths were attributed to high sodium intake, which has become the leading dietary risk factor [5]. Current research has confirmed that high salt intake is a risk factor for various diseases. High sodium intake, one of the most significant risk factors for AF/AFL, has led to a considerable global disease burden [6]. Sodium intake remains high after the implementation of salt reduction campaigns in China; however, it decreased from 6.3 to 4.1 g/d (from 16.0 to 10.4 g/d for salt intake) between 1991 and 2015 [7]. Research demonstrates that the prevalence of atrial fibrillation among individuals aged 45 y and older in China is 1.8%, of which 34.7–46.1% of the patients were unaware of the condition, and only 6% of high-risk patients received anticoagulation therapy [8]. Atrial fibrillation may lead to stroke, heart failure, cognitive decline, dementia, and other diseases, as well as an increase in all-cause mortality, with stroke being the most commonly occurring and most harmful [9].

An increase in salt intake has led to an increasing incidence of diseases in China [10,11,12]. Currently, no research has examined the effect of high salt intake within the AF/AFL population. Therefore, the current study primarily aims to explore and compare the temporal trends in age-standardized mortality rates (ASMRs) or DALY rates (ASDRs) for AF/AFL attributable to high sodium intake in China from 1990 to 2019. This analysis is based on data from GBD 2019, using both Joinpoint regression and age–period–cohort methods.

Methods

Data sources

Raw data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database, accessed via the Global Health Data Exchange query tool (http://ghdx.healthdata.org/gbd-resultstool), a Web-based source. The comprehensive contents and methodology used in GBD 2019 have been published previously [9, 10]. The waiver of informed consent was reviewed and approved by the University of Washington Institutional Review Board, given the use of de-identified aggregated data in GBD 2019.

The International Classification of Diseases and Injuries (ICD-9 and ICD-10) was employed for the identification of AF/AFL. All cardiovascular diseases coded as 427.3– 427.32 in the ICD-9 and I48–I48.92 in the ICD-10 were identified as AF/AFL in the study. Similar to previous GBD research, the current study used an electrocardiogram to diagnose AF/AFL. AF/AFL population data in China were screened from the database. Years of life lost (YLLs) were calculated as the standard life expectancy at the age of death, multiplied by the number of deaths. Years lived with disability (YLDs) were estimated as the number of YLLs to health, weighted by disability weight for severity. DALYs were derived by adding YLLs and YLDs due to premature death of the population [2,3,4,5,6,7,8,9,10,11,12,13].

Sodium intake among the Chinese population in GBD 2019 was estimated from 9 Chinese studies. These studies included the China Nutrition Survey in 1992 and 2002, as well as the KaiLuan Study conducted from 2006 to 2016. The data were then converted into 24-hour urinary sodium (the gold standard data source of GBD 2019) by using a Bayesian meta-regression tool. The mean sodium intake, stratified by age, sex, country, and year, was estimated using a spatiotemporal Gaussian process regression framework based on all available data sources. High sodium intake was defined as sodium intake > 5 g/d [5]. In addition, the Social Development Index (SDI), a composite indicator of the social and economic background conditions influencing health outcomes, is also provided [14].

Statistical analysis

The age-standardized rate per 100,000 population, in accordance with the direct method, is calculated by summing the products of age-specific rates ($\:{a}_{i}$, where $\:i\:$denotes the $\:{i}^{tℎ}$ℎ}\) age class) and the corresponding number of individuals (or weight) ($\:{w}_{i})$ in the same age subgroup $\:i\:$of the chosen reference standard population. The outcome is then divided by the sum of standard population weights, as follows:

$ASR=\frac{{\sum\nolimits_{{i=1}}^{A} {{a_i}{w_i}} }}{{\sum\nolimits_{{i=1}}^{A} {{w_i}} }} \times 100,000$

For ASMR or DALY rates (ASDR), a generalized linear model with a Gaussian distribution was used to quantify the temporal trends in the global burden of AF/AFL attributable to high sodium intake. The age-standardized population is calculated using the GBD World Population Age Standards. Age-standardized mortality and DALYs were calculated with 95% uncertainty intervals (UI) to estimate the burden of disease. Uncertainty intervals consider not only the variance of the parameter estimates but also the uncertainty within the parameter estimates. This uncertainty in parameter estimation includes data collection and model selection choices [15].

The joinpoint regression model was used to appreciate the time trends of AF/ADL attributable to high sodium intake from 1990 to 2019. This model divided the long-term trends into segments and further determined the trends with statistical significance within different segments [16]. The average annual percentage change (AAPC), the annual percentage change (APC) for each segment, and the 95% CIs were estimated to indicate the direction and magnitude of the trends.

In the age–period–cohort analysis, the population was arranged into consecutive 5-year periods from 1990 to 2019 and successive 5-year age groups (30–34 to 90–94). High sodium intake attributable to AF/AFL in individuals aged < 30 y was rare, and all individuals aged ≥ 95 y were recorded as one group in the GBD 2019 database; thus, they were excluded from this study. Joinpoint analysis was conducted using the software Joinpoint v. 4.8.0.1 (April 2020) from the National Cancer Institute (Rockville, MD). Data analysis and visualization were performed using the software R v. 4.0.2. The R packages employed in the present study included “factoextra,” “dplyr,” “tidyverse,” “ggplot,” and “stats.” A p-value < 0.05 was considered statistically significant.

Results

In 2019, the number of AF/AFL deaths and DALYs attributable to high sodium intake were 4209.944 (95% UI: [1250.69-8718.238]) and 235484.586 (95% UI: [89136.783-428566.694]), with males comprising 44.81% and 51.95% of cases, respectively. The ASMR was 0.268 (95% UI: [0.069–0.579]) per 100,000 population, and the ASDR was 11.713 (95% UI: [4.255–21.658]) per 100,000 population (Table 1). The proportions of AF/AFL deaths and DALYs attributable to high sodium intake to the total number of AF/AFL deaths and DALYs were 4.89% and 6.65% in 2019, respectively (S-Fig. 1).

Table 1 Number and ASR ofHigh Sodium-related atrial fibrillation and flutter death and DALYs between 1990 and 2019

The AF/AFL deaths and DALYs attributable to high sodium intake increased between 1990 and 2019 for both males and females. The ASMRs and ASDR for AF/AFL due to high sodium exhibited an upward trend in 2017 and 2007, respectively (Fig. 1). Relative to those in 1990, the ASMRs and ASDRs for AF/AFL due to high sodium increased in both females and males in 2019 (S-Fig. 2). The ASMRs and ASDRs decreased with increasing SDI, with correlations of -0.91 and − 0.99, respectively (S-Fig. 3).

Fig. 1

Trends in death and DALYs of AF/AFL attributable to high sodium intake from 1990 to 2019. A: Trends in the number of deaths in China, 1990–2019. B: Trends in the ASMRs in China, 1990–2019. C: Trends in the number of disabled persons in China, 1990–2019. D: Trends in the ASDR in China, 1990–2019

In 2019, the ASMRs and ASDRs for AF/AFL attributable to high sodium rapidly increased after the age of 80–84, and the numbers were lower in females than males. The number of deaths and DALYs showed a downward trend after the 85–89 and 65–69 age groups, respectively. The ASMRs and ASDRs for females are lower than those for males in all age groups. (Fig. 2). The changing trends of ASMRs and ASDR across various age groups from 1990 to 2019 are presented in Figs. 3 and 4. An upward trend was observed in ASMRs for AF/AFL attributable to high sodium due to increased salt intake at ages 30–34, 35–39, and 40–44 (Fig. 3). ASMRs for AF/AFL attributable to high sodium exhibited a rising trend across all age groups (Fig. 4).

Fig. 2

Trends in death and DALYs of AF/AFL attributable to high sodium intake for different age groups in 2019. A: Trends in the number of deaths in different age groups. B: Trends in the ASMRs in different age groups. C: Trends in the number of disabled persons in different age groups. D: Trends in the ASDR in different age groups

Fig. 3

ASMRs in different age groups from 1990 to 2019

Fig. 4

ASDR in different age groups from 1990 to 2019

The trends in ASMRs and ASDR for AF/AFL attributable to high sodium intake are presented in Table 2, In ASDR, both sexes exhibited a rising trend in the 2006–2012 (APC: 1.0236; 95%CI: [0.8766–1.1708] and 2012–2019 periods (APC: 0.1141; 95%CI: [0.0259–0.2023]). Similar to females, the 2006–2015 period (APC: 0.5829; 95%CI: [0.5192–0.6466] and the 2015–2019 period (APC: 0.0662; 95%CI[-0.1204-0.2531]) showed an increasing trend. Females in the 2013–2019 interval (APC: -0.1018; 95%CI: [-0.2215-0.018]) exhibited a decreasing trend. In the 2017–2019 period, both sexes demonstrated a rising trend in ASMRs (APC: 0.5322; 95%CI: [0.1427–1.9262]). In the same period, the females showed an upward trend (APC: 1.0463; 95%CI[0.3439–2.456]). Females between 2012 and 2019 (APC: -0.4580; 95%CI: [-0.7236-0.1917]) showed a decreasing trend. With an increase in age, the AAPC of ASMRs increased, whereas the AAPC of ASDR decreased (Fig. 5).

Table 2 Trends of Age-standardized mortality rates and of DALYs Rate for Atrial fibrillation and flutter attributable to High Salt Intake from 1990 to 2019 in China using join-point regression

Fig. 5

Longitudinal age curves of high sodium intake-attributable AF and AFL in China. A: Trends in the ASMRs in China. B: Trends in the ASDR in China

Discussion

In this study, we found that the ASMRs and ASDRs for AF/AFL due to high salt intake were relatively pronounced, with males showing higher rates than females and ASMRs and ASDRs gradually decreasing. Therefore, controlling high salt intake is an effective approach to preventing AF/AFL.

Currently, the main risk factors for AF/AFL include old age, obesity, hypertension, diabetes, myocardial infarction, heart failure, smoking, genetic susceptibility, and so on. These risk factors coincide with those of other cardiovascular and cerebrovascular chronic diseases, posing a threat to the health of residents [17]. The demographic shift toward an increasingly older population in China has led to rising incidence and prevalence of AF due to increases in unhealthy lifestyles, life and work pressure, bad eating habits, and unhealthy dietary patterns [16]. The current study found that high salt intake can cause AF/AFL, particularly in women and the elderly, which finding is consistent with previous studies [18,19,20].

The results of this study showed that the ASMRs and ASDRs of AF/AFL due to high salt intake were lower in the Chinese female population than in the male population in all age groups. These results suggest that reducing the burden of disability due to AF/AFL heart failure disease by lowering dietary salt may be more effective for male. Therefore, salt reduction education should be strengthened for key populations, and effective salt reduction measures should be explored to increase health awareness and improve the health status of the population. Simultaneously, the disability rate of AF/AFL due to high salt intake increased from age 40 y, indicating a shift in incidence toward younger age groups. Previous studies have shown that the prevalence of AF/AFL in Chinese residents aged ≥ 35 y increased from 0.66% in 2004 to 0.71% in 2018, higher than that in Japan, South Korea, and other countries. In addition, the number of new patients has consistently risen, contributing to the increasing disease burden of AF/AFL in China [21].

Using Joinpoint regression analysis, this study found an upward trend in the disability rate of AF/AFL due to excessive salt intake in Chinese residents from 2012 to 2019. The mortality rate associated with AF/AFL due to excessive salt intake exhibited a rising trend from 2017 to 2019. A potential continuation of such a trend in the future is suggested. Therefore, the burden of AF/AFL can potentially increase, causing an increased load on AF/AFL treatment. The normalization and efficacy of AF/AFL treatment in China require further enhancement. Standardized treatment for AF/AFL should prioritize improving the rate of anticoagulation treatment, standardizing diagnosis and treatment plans, and enhancing patient compliance, all while reducing the bleeding risk for patients. Second, the risk factors of patients with AF/AFL require effective control to reduce the incidence of AF/AFL, to lower the morbidity and mortality of atrial AF/AFL [22, 23].

The cardiovascular effect on AF/AFL also needs to be considered. In a prospective AF/AFL cohort study, a small left ventricle was independently associated with an increased risk of cardiovascular events, which are factors in the risk stratification and management of patients with AF/AFL [24]. The anticoagulant treatment rates for AF/AFL patients in China are 29.12% and 11.44%, which are lower than the rates in the United States (76%) and Europe (80.5%) [19]. Therefore, the early screening and adherence to standardized anticoagulation treatment rates for patients with AF/AFL need to be further strengthened. Patients with AF/AFL require additional anticoagulation therapy because dual antiplatelet therapy is not sufficient to reduce the risk of stroke in patients with AF. However, combining anticoagulants with dual antiplatelet therapy also significantly increases the risk of bleeding. Therefore, the optimal combination of antiplatelet therapy and oral anticoagulants in this scenario prompts considerable interest, with the aim of reducing the risk of stent thrombosis, recurrent myocardial infarction, and stroke while minimizing the risk of bleeding [25].

This study elucidated the temporal trends in AF/AFL mortality and DALYs attributable to high sodium intake in China, using data from the GBD 2019 study. The GBD study provides the latest data and internally consistent estimates specific to age, sex, location, and year for both all-cause and cause-specific mortality, ensuring a satisfactory quality that reduces the possibility of outcome misclassification. This study has certain limitations. First, 24 h urinary sodium is the currently recognized gold standard for assessing sodium intake levels [26, 27], this assessment used per capita dietary sodium intake to estimate sodium intake levels. This method may introduce bias into the study outcomes, and a delayed effect could exist in the association of sodium intake levels with AF/AFL disease data in the population over the same period. Although the current study used ICD codes to extract AF/AFL from the GBD database, the use of administrative data may have biased the analysis. Thus, the prevalence of asymptomatic paroxysmal AF/AFL is often underestimated in practical scenarios, potentially leading to a decrease in the number of AF/AFL cases due to high salt intake. Second, the study only analyzed high-salt diet as a single factor and did not consider the combined effects of various risk factors, hence the deviations in the results.

In conclusion, our findings provide strong evidence that high sodium intake in China affects alterations in ASMRs and ASDR for AF/AFL over the past 30 years. This finding suggests that strict implementation of effective salt reduction strategies is crucial in China for AF/AFL prevention, particularly among the elderly population and males.