Nutrition-related Diseases and Cardiovascular Mortality in American Society: National Health and Nutrition Examination Study, 1999-2006

doi:10.21203/rs.3.rs-1630729/v1

Download PDF

Research Article

Nutrition-related Diseases and Cardiovascular Mortality in American Society: National Health and Nutrition Examination Study, 1999-2006

https://doi.org/10.21203/rs.3.rs-1630729/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background: Despite many significant advances in treatment and management, cardiovascular disease (CVD) remains the main cause of the global disease burden. Nutrition-related disease is a modifiable cardiovascular risk factor. However, few studies have examined the relationship between nutrition-related diseases and cardiovascular mortality in community populations.

Objective: We aimed to investigate the association of nutrition-related diseases with cardiovascular mortality based on a large nationally representative community population.

Design: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 with mortality follow-up through December 31, 2015. Finally, 12,529 participants were analyzed. Each participant was assigned to one of four groups: normal nutrition without sarcopenia, sarcopenia with normal nutrition, malnutrition without sarcopenia, and malnutrition-sarcopenia syndrome. Survival curves and Cox regressions based on the NHANES recommended weights were used to assess the association between nutrition-related diseases and cardiovascular mortality.

Results: Of the 12,529 patients included in the study and divided into four groups, malnutrition-sarcopenia syndrome had the highest 5- and 10-year cardiovascular mortality rates (17 of 318, 5.4%; 33 of 318, 10.4%). After adjustment for related factors, sarcopenia with normal nutrition (hazard ratio [HR]: 1.68, 95% confidence interval [CI]:1.35−2.09; P < 0.001), malnutrition without sarcopenia (HR: 1.48, 95% CI:1.18−1.84; P < 0.001), and malnutrition-sarcopenia syndrome (HR: 2.41, 95% CI:1.63−3.56; P < 0.001) were significantly associated with increased risk of all-cause mortality. Malnutrition-sarcopenia syndrome remained associated with an increased risk of cardiovascular mortality (HR: 3.69, 95% CI: 1.92−7.23; P < 0.001).

Conclusions: Malnutrition-sarcopenia syndrome was highly prevalent among community-dwelling adults in the United States and was a strong prognostic factor for cardiovascular mortality in the community setting. Randomized clinical trials are needed to demonstrate whether prevention or treatment of malnutrition-sarcopenia syndrome in community populations can reduce global cardiovascular mortality.

Nutrition-related diseases

Malnutrition-sarcopenia syndrome

Cardiovascular mortality

Society

NHANES

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for 27% of global deaths (1, 2). Despite many significant advances in treatment and management, CVD remains the main cause of the global disease burden (3).

There is a growing focus on primary prevention and on reducing the burden of CVD by treating other comorbidities, rather than focusing on the prevention and treatment of CVD itself. Lifestyle changes related to smoking, diet, and exercise can prevent premature cardiovascular events (4, 5). Recent studies have shown that treating conditions such as hyperlipidemia or depression could reduce cardiovascular mortality (6–8). Therefore, it is possible to prevent, detect, and treat other diseases associated with cardiovascular mortality to reduce the global burden of CVD.

Malnutrition and sarcopenia are highly prevalent in the global elderly population (9, 10). These conditions are closely related to premature death and cardiovascular mortality (11, 12). Similarly, recent studies have shown that malnutrition-sarcopenia syndrome was equally prevalent in hospitalized older adults and is associated with high mortality (13, 14). The advantage of nutrition-related disease over other clinical variables is that it is a modifiable risk factor that physicians can act on (15). However, the current study is limited to the inpatient population only, while the community population has a much larger base of people with nutrition-related diseases (16). Few studies have examined the relationship between nutrition-related diseases and cardiovascular mortality in community populations.

This study aimed to investigate the association of nutrition-related diseases with cardiovascular mortality based on a large nationally representative community population and further to establish a theoretical basis for the possibility of preventing or treating nutrition-related diseases in community populations through some easily achievable measures to reduce global cardiovascular mortality.

Study population

National Health and Nutrition Examination Survey (NHANES) is a nationally representative health survey designed and administered by the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention (CDC). The NHANES was designed to represent the civilian non-institutionalized United States population using a complex multistage probability sampling methodology. We conducted a retrospective analysis of a cohort of US population of the NHANES. As shown in Figure 1, this study included participants ≥ 20 years of age during NHANES 1999−2006 (n = 20,311). Of these participants, 7,782 were excluded based on the lacked available true dual-energy x-ray absorptiometry (DXA) and body composition measurement data, lack of measured albumin level, or loss to follow-up. Thus, 12,529 patients were enrolled in the present study.

Screening for nutrition-related diseases

Whole body DXA scans were acquired using model QDR-4500A fan-beam densitometers (Hologic, Inc, Bedford, MA) in NHANES participants over 8 years of age. DXA exclusion criteria included pregnancy, weight >300 pounds (136 kg, weight limit of the scanner), height over 6.5 feet (length of DXA table), use of the barium radiographic contrast material in the preceding 7 days, or nuclear medicine studies in the past 3 days.

Appendicular skeletal muscle mass was measured using DXA. The sarcopenia index was calculated as total appendicular skeletal muscle mass (in kg)/body mass index (BMI, kg/m²). Sarcopenia was defined as the lowest quintile for sex-specific sarcopenia index cut-off values (0.789 for men and 0.512 for women), based on a modified recommendation from the Foundation for the National Institutes of Health (17).

The nutritional risk index (NRI) is a nutritional assessment score that has become popular in recent years due to its simplicity, objectivity, and strong prognostic value for different medical and patient populations. NRI was calculated as (1.519 × serum albumin (g/l)) + 41.7 × (current body weight [kg]/usual body weight [kg]) (18). According to a previous study (19), patients were classified into two nutritional risk categories: nutritional risk (NRI < 100) and no nutritional risk (NRI ≥ 100).

Definitions of variables of interest

Age, sex, race, smoking status, education level, smoking status, alcohol use, and histories of congestive heart failure (CHF), coronary heart disease (CHD), diabetes mellitus (DM), hypertension, and cancer were self-reported. Diagnosis of comorbidities was based on an affirmative response to the question, “Has a doctor or other health professional ever told you that you had (CHF, CHD, DM, hypertension and cancer)?”

Primary outcome

Mortality status was determined based on a probabilistic record match with the National Death Index (NDI) using demographic identifiers. (Available at: http://www.cdc.gov/nchs/data/datalinkage/nh99+_mortality_matching_methodology_final.pdf. Accessed July 22, 2010.). The primary outcome was cardiovascular mortality. The secondary outcome was all-cause mortality. Cause of death was categorized using the International Classification of Diseases 10th edition (ICD-10). Cardiovascular mortality was categorized using ICD-10 codes I00–I078. For participants in NHANES 1999-2006, mortality follow-up data was available through December 31, 2015.

Statistical analyses

NHANES recommended weights were used to account for planned oversampling of specific groups. The continuous variables are expressed as the mean ± standard deviation. Categorical variables are expressed as counts (percentages). Baseline characteristics between the four groups were compared using an ANOVA for continuous variables and a χ2 test for categorical variables.

Each patient was assigned to one of four groups: normal nutrition without sarcopenia, sarcopenia with normal nutrition, malnutrition without sarcopenia, and malnutrition-sarcopenia syndrome. To evaluate the association between nutrition-related diseases and mortality, we used Kaplan-Meier estimates based on the NHANES recommended weights to calculate cumulative survival probabilities for cardiovascular mortality and all-cause mortality, and univariate and multivariate cox regression analyses based on the NHANES recommended weights. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Model 1 was a crude model unadjusted for potential confounders. Model 2 was adjusted for demographic factors, including age, sex, and race/ethnicity. Model 3 was further adjusted for education level, smoke status, alcohol status, BMI, CHF, CHD, DM, hypertension, and cancer. We further explored the relationship between different malnutrition status and mortality in different subgroups (age, sex, race/ethnicity, CHF, DM, hypertension, and cancer). Participants were divided into age, sex, and obesity subgroups. We explored the relationship between nutrition-related diseases and cardiovascular mortality in different subgroups.

All analyses were performed using R software (version 4.0.3; R Foundation for Statistical Computing, Vienna, Austria). A two-sided P-value <0.05 indicated the significance for all analyses.

Patient characteristics

In total, 12,529 participants remained in the study. They were divided into four groups based on the combined presence of malnutrition or sarcopenia. The distribution of the four groups were normal nutrition without sarcopenia (n = 9,353), sarcopenia with normal nutrition (n = 1,378), malnutrition without sarcopenia (n = 1,480), and malnutrition-sarcopenia syndrome (n = 318), respectively. Participants in the malnutrition-sarcopenia syndrome were older (61.4 ± 1.0 years) and more likely to be female (59.8%). Non-Hispanic Blacks were more prevalent in the malnutrition without sarcopenia group (19.4%) and less prevalent in the malnutrition-sarcopenia syndrome group (4.0%). There were no significant differences in smoking among the four groups (P = 0.542). Concerning BMI, compared to normal nutrition without sarcopenia (27.0 ± 0.1 kg/m²) and malnutrition without sarcopenia (27.6 ± 0.3 kg/m²), BMI was significantly higher for those in the sarcopenia with normal nutrition group (31.3 ± 0.2 kg/m², P < 0.001) and malnutrition-sarcopenia syndrome group (32.2 ± 0.5 kg/m², P < 0.001). Participants in the malnutrition-sarcopenia syndrome group were more likely to have hypertension (55.4%) and DM (22.7%), CHD (13.0%), CHF (9.5%), and cancer (18.1%). The baseline characteristics of the study subjects at entry are summarized in Table 1.

Table 1

Baseline characteristics of the study population (weighted)
	Normal nutrition without sarcopenia (n = 9,353)	Sarcopenia with normal nutrition (n = 1,378)	Malnutrition without sarcopenia (n = 1,480)	Malnutrition-sarcopenia syndrome (n = 318)	P-value
Age	43.4 ± 0.3	56.2 ± 0.6	47.0 ± 0.5	61.4 ± 1.0	< 0.001
Female	4268 (47.1)	590 (43.4)	1074 (78.7)	184 (59.8)	< 0.001
Race
Mexican American	1970 (7.1)	637 (16.7)	188 (4.6)	121 (12.8)	< 0.001
Other Hispanic	415 (5.2)	85 (9.7)	52 (4.3)	13 (5.5)
Non-Hispanic White	4915 (74.3)	575 (65.2)	676 (66.9)	157 (74.9)
Non-Hispanic Black	1718 (8.9)	33 (1.4)	509 (19.4)	20 (4.0)
Other Race	335 (4.5)	48 (7.0)	55 (4.8)	7 (2.9)
Education levels
< 12	4766 (42.2)	1001 (62.4)	781 (46.4)	220 (58.2)	< 0.001
12	2596 (30.9)	241 (24.3)	435 (31.7)	65 (29.5)
> 12	1981 (27.0)	132 (13.3)	262 (21.9)	33 (12.3)
Smoking status	4749 (50.1)	679 (48.9)	740 (48.8)	158 (45.8)	0.542
Alcohol*	2.9 ± 0.1	2.8 ± 0.1	2.6 ± 0.1	2.2 ± 0.2	0.026
BMI	27.0 ± 0.1	31.3 ± 0.2	27.6 ± 0.3	32.2 ± 0.5	< 0.001
Hypertension	2384 (22.3)	575 (41.9)	540 (30.6)	158 (55.4)	< 0.001
DM	637 (4.5)	227 (14.8)	183 (9.2)	225 (22.7)	< 0.001
CHD	284 (2.2)	105 (8.6)	63 (3.2)	33 (13.0)	< 0.001
CHF	150 (1.1)	77 (5.5)	61 (2.9)	30 (9.5)	< 0.001
Cancer	614 (6.1)	121 (8.4)	143 (10.3)	47 (18.1)	< 0.001
*The average number of drinks consumed per day over the past 12 months.
Abbreviations: BMI, body mass index; DM, diabetes mellitus; CHD, coronary heart disease; CHF, congestive heart failure

All-cause And Cardiovascular Mortality

The normal nutrition without sarcopenia had the lowest cumulative 5-year all-cause mortality (344 of 9,353, 3.7%) and cardiovascular mortality (65 of 9,353, 0.6%). Malnutrition-sarcopenia syndrome was associated with the highest 5-year all-cause mortality (70 of 318, 22.0%) and the greatest prevalence of cardiovascular mortality (17 of 318, 5.4%). Similar to the cumulative 5-year mortality, the normal nutrition without sarcopenia group had the lowest 10-year cumulative all-cause mortality (836 of 9,353, 8.9%) and cardiovascular mortality (141 of 9353, 1.5%). The malnutrition-sarcopenia syndrome group had the highest 10-year all-cause mortality (126 of 318, 39.6%) and cardiovascular mortality (33 of 318, 10.4%) (Fig. 2). The Kaplan-Meier survival analysis curves revealed significantly lower long-term survival rates for patients with any form of malnutrition and sarcopenia, including malnutrition-sarcopenia syndrome, compared with patients with no malnutrition and sarcopenia (Fig. 2). Univariate Cox proportional risk analysis revealed independent associations with increased risk of all-cause mortality for sarcopenia with normal nutrition (HR: 3.81, 95% CI: 3.26 − 4.45; P < 0.001), malnutrition without sarcopenia (HR: 2.18, 95% CI: 1.84 − 2.58; P < 0.001), and malnutrition-sarcopenia syndrome (HR: 6.54, 95% CI: 5.20 − 8.24; P < 0.001).Independent association with increased risk of cardiovascular mortality was evident for malnutrition without sarcopenia (HR: 1.60, 95% CI: 1.10 − 2.33; P = 0.013) and malnutrition-sarcopenia syndrome (HR: 2.71, 95% CI: 1.45–5.06; P = 0.002). Even after adjusting for age, gender, race, education level, smoke status, alcohol, BMI, CHF, CHD, DM, hypertension, and cancer, significant associations with increased risk of all-cause mortality were evident for sarcopenia with normal nutrition (HR: 1.68, 95% CI:1.35 − 2.09; P < 0.001), malnutrition without sarcopenia (HR: 1.48, 95% CI:1.18 − 1.84; P < 0.001), and malnutrition-sarcopenia syndrome (HR: 2.41, 95% CI:1.63 − 3.56; P < 0.001). Malnutrition-sarcopenia syndrome remained associated with an increased risk of cardiovascular mortality (HR: 3.69, 95% CI: 1.92 − 7.23; P < 0.001) (Table 2).

Table 2

All-cause and cardiovascular mortality hazard ratios (HRs) for participants aged 20 years and older according to nutrition-related diseases: NHANES survey 1999 to 2006 with follow-up through 2015
Models	All-cause mortality			Cardiovascular mortality
Models	HR	95% CI	P-value	HR	95% CI	P-value
Model 1
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	3.81	3.26–4.45	< 0.001	1.31	0.82–2.10	0.256
Malnutrition without sarcopenia	2.18	1.84–2.58	< 0.001	1.60	1.10–2.33	0.013
Malnutrition-sarcopenia syndrome	6.54	5.20–8.24	< 0.001	2.71	1.45–5.06	0.002
Model 2
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.48	1.28–1.71	< 0.001	1.19	0.75–1.89	0.461
Malnutrition without sarcopenia	1.78	1.51–2.01	< 0.001	1.72	1.16–2.55	0.007
Malnutrition-sarcopenia syndrome	2.17	1.75–2.69	< 0.001	2.54	1.37–4.71	0.003
Model 3
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.68	1.35–2.09	< 0.001	1.04	0.52–2.03	0.907
Malnutrition without sarcopenia	1.48	1.18–1.84	< 0.001	1.65	0.94–2.82	0.066
Malnutrition-sarcopenia syndrome	2.41	1.63–3.56	< 0.001	3.69	1.92–7.23	< 0.001
Model 1: No adjustments.
Model 2: Adjusted by age, sex, and race.
Model 3: Adjusted by age, sex, race, education level, smoke status, alcohol, BMI, CHF, CHD, DM, hypertension, and cancer.

Subgroups

When participants were stratified by age and sex, the association between malnutrition-sarcopenia syndrome and risk of all-cause and cardiovascular mortality did not change. However, the association between malnutrition-sarcopenia syndrome and cardiovascular mortality was different when stratified by obesity. There was no significant association between malnutrition-sarcopenia syndrome and cardiovascular mortality in non-obese participants (HR: 2.83, 95% CI: 0.89 − 7.27; P = 0.051). In contrast, a significant association was evident between malnutrition-sarcopenia syndrome and cardiovascular mortality in obese participants (HR: 4.47, 95% CI: 1.65 − 12.10; P = 0.003) (Table 3).

Table 3

All-cause and cardiovascular mortality hazard ratios (HRs) in different subgroups
Variable	All-cause mortality			Cardiovascular mortality
Variable	HR	95% CI	P-value	HR	95% CI	P-value
Age
< 65
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	2.83	2.02 − 3.96	< 0.001	0.59	0.23–1.50	0.269
Malnutrition without sarcopenia	1.76	1.29 − 2.39	< 0.001	0.86	0.24–3.05	0.812
Malnutrition-sarcopenia syndrome	3.93	1.78 − 8.65	< 0.001	6.22	2.09–18.51	0.001
≥ 65
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.82	1.34 − 2.46	< 0.001	1.64	0.79–3.42	0.183
Malnutrition without sarcopenia	1.21	0.88 − 1.64	0.239	2.15	1.17–3.96	0.014
Malnutrition-sarcopenia syndrome	3.19	2.05 − 4.96	< 0.001	4.21	1.62–10.93	0.003
Sex
Male
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.67	1.30 − 2.15	< 0.001	0.88	0.38–2.05	0.771
Malnutrition without sarcopenia	1.74	1.22 − 2.47	0.002	1.43	0.65–3.15	0.372
Malnutrition-sarcopenia syndrome	2.49	1.55 − 4.01	< 0.001	3.04	1.31–7.04	0.009
Female
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.82	1.15 − 2.89	0.010	1.92	0.81–4.60	0.141
Malnutrition without sarcopenia	1.34	0.96 − 1.87	0.088	2.67	1.16–6.16	0.021
Malnutrition-sarcopenia syndrome	2.35	1.48 − 3.72	< 0.001	5.79	1.36–24.70	0.018
Obesity
Non-obese
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.77	1.40 − 2.24	< 0.001	1.36	0.64–2.84	0.431
Malnutrition without sarcopenia	1.64	1.26 − 2.13	< 0.001	1.66	0.91–3.05	0.095
Malnutrition-sarcopenia syndrome	2.23	1.50 − 3.31	< 0.001	2.83	0.89–7.27	0.051
Obese
(Normal nutrition without sarcopenia as reference)
Sarcopenia with normal nutrition	1.37	0.97 − 1.93	0.073	0.54	0.20–1.43	0.216
Malnutrition without sarcopenia	1.07	0.63 − 1.81	0.799	0.81	0.16–4.22	0.804
Malnutrition-sarcopenia syndrome	2.29	1.19 − 4.40	0.013	4.47	1.65–12.10	0.003
Analyses were adjusted for age, sex, race, education level, smoke status, alcohol, BMI, CHF, CHD, DM, hypertension, and cancer.

In this large retrospective study of community populations in the United States, malnutrition-sarcopenia syndrome was associated with an increased risk of cardiovascular mortality and all-cause mortality. Compared to patients without malnutrition and sarcopenia, patients with malnutrition-sarcopenia syndrome had an almost 4-fold increased risk of cardiovascular mortality and an almost 3-fold increased risk of all-cause mortality. Even though both sarcopenia with normal nutrition and malnutrition without sarcopenia were associated with an increased risk of all-cause mortality, neither sarcopenia with normal nutrition alone nor malnutrition without sarcopenia increased the risk of cardiovascular mortality.

CVD is the leading cause of death worldwide (20). To reduce the burden of CVD, many studies have proposed various interventions. These include increased treatment of hypertension and reduced intake of trans fatty acids and sodium, which could save nearly 100 million lives over 25 years. However, this is only a small fraction of the estimated number of cardiovascular deaths over the next 25 years (21). In spite of interventions, the number of cardiovascular mortalities increased by 50% in 2019 compared to 1990. This highlights the continued need for additional prevention efforts to reduce deaths from CVD (22). Nutrition-related diseases are an important risk factor for death from CVD (23). Furthermore, hospitalized patients with nutrition-related diseases have a higher risk of cardiovascular mortality than those without nutrition-related diseases (24, 25). However, inpatients are only a small portion of the global community population. Malnutrition and sarcopenia are prevalent in community populations (16) and always occur together. In one study, low muscle mass was highly prevalent in community-dwelling older adults at risk for malnutrition, with an incidence exceeding 50% (26). The total number of community-dwelling individuals with malnutrition-sarcopenia syndrome is approximately 6% and is increasing worldwide (27–29). Therefore, there is an urgent need to explore whether controlling nutrition-related diseases in community populations can reduce cardiovascular mortality to help reduce the global burden of CVD.

Our results suggested that malnutrition-sarcopenia syndrome was independently associated with an increased risk of all-cause and cardiovascular mortality in community populations in the US. Sarcopenia is considered an important risk factor for cardiovascular mortality in community-dwelling women (30). In contrast, we observed that sarcopenia alone did not appear to affect cardiovascular mortality. However, sarcopenia combined with malnutrition was an important risk factor for cardiovascular death, regardless of gender. The prevalence of obesity has increased dramatically over the past three decades (31). Prior data have associated obesity and nutrition-related diseases in individuals with CVD (32). Therefore, we performed an exploratory subgroup analysis of obesity and found that malnutrition-sarcopenia syndrome influenced cardiovascular mortality only in the obese subgroup. Similarly, in the 5th Korean National Health and Nutrition Examination Survey, non-obese sarcopenic patients not associated with an increased 10-year risk of CVD as determined using the Framingham risk model (33). Nevertheless, considering the high prevalence of nutrition-related diseases and obesity in the community population, this area deserves further investigation. Regardless, we suggest that the incidence of cardiovascular mortality can be reduced by screening and intervention for malnutrition-sarcopenia syndrome in community populations.

Malnutrition leads to CVD in a number of ways. For example, malnutrition can cause autonomic nervous imbalances, leading to high blood pressure and an increased heart rate (34). Malnutrition can also cause insulin resistance and low-grade systemic inflammatory response, which can accelerate the progression of coronary atherosclerosis (35, 36). In addition to malnutrition, sarcopenia can lead to CVD through these pathways. Furthermore, in addition to being associated with inflammation, sarcopenia can negatively affect the body by affecting the distribution of glucose in the muscles (37–39). Previous studies have shown that poor nutrition can worsen sarcopenia, which in turn can worsen the body's nutritional status, forming a vicious cycle (40–42). This cycle may further increase the risk of cardiovascular mortality in patients with malnutrition-sarcopenia syndrome.

Our study confirmed that malnutrition-sarcopenia syndrome was an independent factor of CVD adverse events in community populations. Therefore, we recommend screening for malnutrition-sarcopenia syndrome in community populations. Interestingly, patients with malnutrition-sarcopenia syndrome in nursing homes display higher all-cause mortality than the consecutively admitted older patients with malnutrition-sarcopenia syndrome (14, 43). Perhaps hospitals pay more attention to patients' nutritional status than nursing homes do. In support of this idea, we found that the consecutively admitted older patients are more likely to use nutritional supplements than patients from nursing homes. The benefits of nutritional supplements for malnutrition and sarcopenia have been previously demonstrated (44, 45). In addition, appropriate nutritional interventions can prevent and reverse atherosclerosis, and lessen CVD risk factors (46). Therefore, we recommend enhanced use of nutritional supplements for those who develop nutrition-related diseases in the community. Because community-dwelling individuals tend to be more athletic than hospitalized patients, we also recommend exercise interventions in the community, which can maintain or enhance muscle mass (47).

There were several limitations of this study. The primary limitation was that we did not collect handgrip strength on study participants and only used appendicular skeletal muscle mass to define sarcopenia. However, this definition is commonly recognized and used in studies (48). A second limitation was that information on comorbid health conditions was self-reported. This likely underestimated the prevalence of comorbidities. Finally, only one assessment method, NRI, was used to assess the malnutrition level of patients. Thus, the data may be biased. However, NRI has higher objectivity and accuracy compared with other evaluation methods. The strength of this study was its novelty in exploring the relationship between nutrition-related disease and cardiovascular mortality using a large national community sample.

In summary, sarcopenia or malnutrition alone was not associated with cardiovascular mortality. However, malnutrition-sarcopenia syndrome was highly prevalent among community-dwelling US adults and was a strong prognostic factor for premature cardiovascular mortality among these adults. This suggested that malnutrition-sarcopenia syndrome in community populations could likely be prevented or treated with some easily achievable measures. This would reduce global cardiovascular mortality. However, randomized clinical trials are necessary to demonstrate efficacy and to clarify this point.

Cardiovascular disease (CVD), National Health and Nutrition Examination Survey (NHANES), dual-energy x-ray absorptiometry (DXA), nutritional risk index (NRI), congestive heart failure (CHF), coronary heart disease (CHD), diabetes mellitus (DM), Classification of Diseases 10th edition (ICD-10), hazard ratio (HR), body mass index (BMI)

Ethics approval and consent to participate

Informed consent has been obtained from every participant and therefore there was no need for any ethical consent in this study. The NCHS ethics review board has approved the NHANES protocol. All procedures were performed in accordance with the relevant guidelines and regulations.

Consent for publication

Not applicable.

Availability of data and materials

All data are available as publicly accessible datasets through NHANES. It is open and publicly accessible through the following link; https://wwwn.cdc.gov/nchs/nhanes/.

Competing interests

The authors including Weihua Chen, Shanshan Shi, Jiabin Tu, Lihua Liao, Ying Liao, Kaihong Chen, Liling Chen and Rongchong Huang report no conflicts of interest.

Funding

This research was funded and supported by the Longyan City Science and Technology Plan Project (Grant number:2015LY33), Young and Middle-aged expert Fund for Outstanding Contributions to Hygiene and Health in Fujian Province, and Summit Talent Plan, Beijing Hospital Management Center (Plan No: DFL20190101).

Authors’ contributions

RCH: designed the research and is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; WHC: conducted analyses and wrote the first draft of the paper; WHC, SSS, JBT, LHL, YL, KHC, LLC and RCH: revised the manuscript

Dendale P. Report on Cardiovascular Disease Prevention Summit. European Heart Journal 2020;41:1381–1382.
Arya S, Khakharia A, Binney ZO et al. Association of statin dose with amputation and survival in patients with peripheral artery disease. Circulation 2018;137:1435–1446.
Pearson J, Sipido KR, Musialek P, van Gilst WH. The cardiovascular research community calls for action to address the growing burden of cardiovascular disease. Cardiovascular research 2019;115:e96-e98.
Arnett DK, Blumenthal RS, Albert MA et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140:e596-e646.
Bhatnagar A. Environmental determinants of cardiovascular disease. Circulation Research 2017;121:162–180.
Hare DL. Depression and cardiovascular disease. Current Opinion in Lipidology 2021;32:167–174.
Kamstrup PR. Lipoprotein(a) and cardiovascular disease. Clinical Chemistry 2021;67:154–166.
Soran H, Adam S, Durrington PN. Optimising treatment of hyperlipidaemia: Quantitative evaluation of UK, USA and European guidelines taking account of both LDL cholesterol levels and cardiovascular disease risk. Atherosclerosis 2018;278:135–142.
Hansikova H, Zeman J, Klement P et al. Deficiency of pyruvate dehydrogenase complex in tissues of an eight month old infant. Biochemistry and Molecular Biology International 1993;31:1157–66.
Shafiee G, Keshtkar A, Soltani A, Ahadi Z, Larijani B, Heshmat R. Prevalence of sarcopenia in the world: a systematic review and meta- analysis of general population studies. Journal of Diabetes and Metabolic Disorders 2017;16:21.
Gielen E, Beckwée D, Delaere A, De Breucker S, Vandewoude M, Bautmans I. Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Nutrition Reviews 2021;79:121–147.
Landi F, Liperoti R, Fusco D et al. Sarcopenia and mortality among older nursing home residents. Journal of the American Medical Directors Association 2012;13:121–6.
Vandewoude MF, Alish CJ, Sauer AC, Hegazi RA. Malnutrition-sarcopenia syndrome: is this the future of nutrition screening and assessment for older adults? Journal of Aging Research 2012;2012:651570.
Hu X, Zhang L, Wang H, Hao Q, Dong B, Yang M. Malnutrition-sarcopenia syndrome predicts mortality in hospitalized older patients. Scientific Reports 2017;7:3171.
Freeman AM, Morris PB, Barnard N et al. Trending cardiovascular nutrition controversies. Journal of the American College of Cardiology 2017;69:1172–1187.
Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. Journal of the American Geriatrics Society 2002;50:889–96.
Studenski SA, Peters KW, Alley DE et al. The FNIH sarcopenia project: Rationale, study description, conference recommendations, and final estimates. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2014;69:547 – 58.
Buzby GP, Williford WO, Peterson OL et al. A randomized clinical trial of total parenteral nutrition in malnourished surgical patients: The rationale and impact of previous clinical trials and pilot study on protocol design. The American Journal of Clinical Nutrition 1988;47:357–65.
Raposeiras Roubín S, Abu Assi E, Cespón Fernandez M et al. Prevalence and prognostic significance of malnutrition in patients with acute coronary syndrome. Journal of the American College of Cardiology 2020;76:828–840.
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet (London, England) 2006;367:1747–57.
Kontis V, Cobb LK, Mathers CD, Frieden TR, Ezzati M, Danaei G. Three public health interventions could save 94 million lives in 25 years. Circulation 2019;140:715–725.
Roth GA, Mensah GA, Johnson CO et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 Study. Journal of the American College of Cardiology 2020;76:2982–3021.
Chien SC, Chandramouli C, Lo CI et al. Associations of obesity and malnutrition with cardiac remodeling and cardiovascular outcomes in Asian adults: A cohort study. PLoS Medicine 2021;18:e1003661.
Hersberger L, Dietz A, Bürgler H et al. Individualized nutritional support for hospitalized patients with chronic heart failure. Journal of the American College of Cardiology 2021;77:2307–2319.
Takahashi H, Ito Y, Ishii H et al. Geriatric nutritional risk index accurately predicts cardiovascular mortality in incident hemodialysis patients. Journal of Cardiology 2014;64:32–6.
Tey SL, Huynh DTT, Berde Y et al. Prevalence of low muscle mass and associated factors in community-dwelling older adults in Singapore. Scientific Reports 2021;11:23071.
Tan VMH, Pang BWJ, Lau LK et al. Malnutrition and sarcopenia in community-dwelling adults in Singapore: Yishun Health Study. The Journal of Nutrition, Health & Aging 2021;25:374–381.
Abd Aziz NAS, Teng N, Abdul Hamid MR, Ismail NH. Assessing the nutritional status of hospitalized elderly. Clinical interventions in Aging 2017;12:1615–1625.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age and Ageing 2010;39:412–23.
Brown JC, Harhay MO, Harhay MN. Sarcopenia and mortality among a population-based sample of community-dwelling older adults. Journal of Cachexia, Sarcopenia and Muscle 2016;7:290–8.
Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet (London, England) 2016;387:1377–1396.
Fukuda T, Bouchi R, Takeuchi T et al. Sarcopenic obesity assessed using dual energy X-ray absorptiometry (DXA) can predict cardiovascular disease in patients with type 2 diabetes: A retrospective observational study. Cardiovascular Diabetology 2018;17:55.
Kim JH, Cho JJ, Park YS. Relationship between sarcopenic obesity and cardiovascular disease risk as estimated by the Framingham risk score. Journal of Korean Medical Science 2015;30:264–71.
Penitente AR, Fernandes LG, Cardoso LM et al. Malnutrition enhances cardiovascular responses to chemoreflex activation in awake rats. Life Sciences 2007;81:609–14.
Zoppi CC, Silveira LR, Oliveira CA, Boschero AC, Curi R, Carneiro EM. Insulin release, peripheral insulin resistance and muscle function in protein malnutrition: A role of tricarboxylic acid cycle anaplerosis. The British Journal of Nutrition 2010;103:1237–50.
Di Pino A, DeFronzo RA. Insulin Resistance and atherosclerosis: Implications for insulin-sensitizing agents. Endocrine Reviews 2019;40:1447–1467.
Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: Mechanistic links between common co-morbidities. The Journal of Endocrinology 2016;229:R67-81.
Lynch GS, Ryall JG. Role of beta-adrenoceptor signaling in skeletal muscle: Implications for muscle wasting and disease. Physiological Reviews 2008;88:729–67.
Can B, Kara O, Kizilarslanoglu MC et al. Serum markers of inflammation and oxidative stress in sarcopenia. Aging Clinical and Experimental Research 2017;29:745–752.
Kaluźniak-Szymanowska A, Krzymińska-Siemaszko R, Deskur-Śmielecka E, Lewandowicz M, Kaczmarek B, Wieczorowska-Tobis K. Malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in older adults with COPD. Nutrients 2021;14(1):44.
Wang YW, Lin TY, Peng CH, Huang JL, Hung SC. Factors associated with decreased lean tissue index in patients with chronic kidney disease. Nutrients 2017;9(5):434.
Inaba M, Mori K. Extension of healthy life span of dialysis patients in the era of a 100-year life. Nutrients 2021;13(8):2693.
Yang M, Huang Z, Chen J, Jiang J, Zuo Y, Hao Q. Applications of the new ESPEN definition of malnutrition and SARC-F in Chinese nursing home residents. Scientific Reports 2018;8:14971.
Campbell WW, Trappe TA, Wolfe RR, Evans WJ. The recommended dietary allowance for protein may not be adequate for older people to maintain skeletal muscle. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2001;56:M373-80.
Kokkinidou S, Peterson D, Bloch T, Bronston A. The important role of carbohydrates in the flavor, function, and formulation of oral nutritional supplements. Nutrients 2018;10(6):742.
Casas R, Castro-Barquero S, Estruch R, Sacanella E. Nutrition and cardiovascular health. International Journal of Molecular Sciences 2018;19(12):3988.
Deutz NE, Bauer JM, Barazzoni R et al. Protein intake and exercise for optimal muscle function with aging: Recommendations from the ESPEN Expert Group. Clinical Nutrition (Edinburgh, Scotland) 2014;33:929–36.
Han E, Lee YH, Kim YD et al. Nonalcoholic fatty liver disease and sarcopenia are independently associated with cardiovascular risk. The American Journal of Gastroenterology 2020;115:584–595.

No competing interests reported.

Download PDF

Editorial decision: Major revision
02 Aug, 2022
Reviews received at journal
13 Jun, 2022
Reviewers agreed at journal
23 May, 2022
Reviewers invited by journal
22 May, 2022
Editor assigned by journal
22 May, 2022
Editor invited by journal
17 May, 2022
Submission checks completed at journal
17 May, 2022
First submitted to journal
06 May, 2022

You are reading this latest preprint version

Nutrition-related Diseases and Cardiovascular Mortality in American Society: National Health and Nutrition Examination Study, 1999-2006

Status:

Version 1

Abstract

Figures

Introduction

Methods

Study population

Screening for nutrition-related diseases

Definitions of variables of interest

Primary outcome

Statistical analyses

Results

Patient characteristics

All-cause And Cardiovascular Mortality

Subgroups

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1