Sarcopenic is associated with hypertension in older adults: a systematic review and meta-analysis

Both sarcopenia and handgrip strength have been observed association with hypertension. However, the results in different studies were inconsistent. In the current study, we conducted a systematic review and meta-analysis to reveal the association between sarcopenia, handgrip strength, and hypertension in older adults. the indicated that sarcopenia was a risk factor for the hypertension. 11 studies focused on the association between handgrip strength and hypertension and no association was found by the pooled results.


Conclusion
Sarcopenia was associated with hypertension but no correlation was found between handgrip strength and hypertension in older adults. Background 3 In 2050, the number of elderly people of the world population is expected to reach about 30% [1]. The aging process is accompanied with alterations in some physiological systems collaborating to the development of geriatric syndromes and chronic diseases.
Hypertension is affecting more than 70% of the older people [2] and show an increased risk of stroke (i.e., hemorrhagic and ischemic) and myocardial infarction [2,3]. In the past few years, number of studies have indicated that hypertension is associated with elevated cardiovascular risk [4][5][6].
Recently, data from population studies have demonstratedthat sarcopenia, a neuromuscular disease characterized by a progressive muscular atrophy accompanied by low muscle strength and/or lower muscle limb function, could be a risk factor of hypertension [7][8][9]. Meanwhile, sarcopenia has been demonstrated have associations with the aging process and can lead to significant morbidity and disability, including loss of independence, poor quality of life, and mortality [10][11][12][13]. Sarcopenia had several contributing factors, such as primarily advanced age, immobility, inadequatenutrition, neurodegenerative disease, malignancy, chronicmultiple endocrine disorders, and cardiometabolic disease. The rate of sarcopenia in the elderly is expected to increase in the future [14]and is becoming a major public health problem [15].
The handgrip strength examination is often applied as a sarcopenia filtering technique in clinical setting such measurement is considered inexpensive, simple, easy, and can be done with portable measuring tool. Up to now, the associations between sarcopeniahandgrip strength, and hypertension in older adults were controversial [7-9, 16, 17]and has not been systemic summarized. Given the hypothesis that sarcopenia could be a risk factor of hypertension, a systemic investigation of on the topic would allow early identification one of the hypertension key risk factors in elderly patients undergoing sarcopenia and conduct prevention or treatment strategies associated with specific 4 vulnerability factors.

Literature Search
The individual and joint keywords of "Handgrip Strength", "grip strength", "sarcopenia", and "hypertension" were conducted for the literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [18]. To include more potential literatures, we kept the search termsas broadly aspossible to identify the relevant publications. A systematic electronic search of PubMed, MEDLINE, Cochrane Library, and EMBASE databases were performed up to 15 November, 2019.
Moreover, the bibliographies of all relevant studies and reviews, and Google Scholar for studies citing relevant studies were also checked and identified.

Eligibility Criteria
The inclusion criteria were as follows: (1) observational studies that addressing the association between sarcopenia and hypertension, or handgrip strength and hypertension; (2) provided clear diagnostic criteria of sarcopenia and hypertension; (3) necessary data extracted from original studies; (4) studies published in English; and (5) only the study provided more detailed information was included if the population was reported in duplicate.
Reviews, case reports, abstracts or posters for conferences, studies focused on animal experiments or experiments in vitro, and studies in languages other than English were also excluded.

Data extraction
Two investigators (TTB and FF) extracted the necessary information of included studies using a customized and standardized form independently, and the consensus were reached on all items by the two authors. For each included study, the following information were extracted: the author and year of publication, country, study design, sample size, patient characteristics (e.g., age, sex, and nation), diagnostic criteria of sarcopenia and hypertension, sample size and characteristics for each group, follow-up period, and outcomes of each group.

Quality scoring of studies
Two reviewers (FKL and JMC) assessed the methodological strength of included studies independently in order to aid interpretation the validity of any findings by the Newcastle-Ottawa Scale (NOS), a procedure to independently assess the methodological quality of for meta-analysis of observational studies [19]. Newcastle-Ottawa Scale included three categories three factors: (1) patient selection (three items); (2) comparability of the two study arms (two items); and (3) assessment of the outcomes (two items). The detailed criteria for the three assessments are: if the cases were defined adequately, the representativeness of the cases, the process of selection and definition for controls, comparability of cases and controls based on the design or analysis, ascertainment of exposure, the same method of ascertainment for cases and controls, and nonresponse rate.
Studies were awarded a maximum of one star for each numbered item within the selection and exposure categories and a maximum of two stars can be given for comparability.
Studies were graded on an ordinal scoring scale. The score was ranged from 2 stars to 9 stars. Therefore, a scale of 0 to 4 stars was considered to be of poor quality, 5 to 6 stars as moderate quality, and 7-9 stars as high quality.

Statistical analysis
The inverse variance method with random effects was conducted to summarize the dichotomous outcomes, odd ratios (ORs), and 95% confidence intervals (CIs). Stratified analyses were also performed with respect to the characteristics of the study population 6 and outcome. Heterogeneity between included studies was assessed using the I 2 and Q tests. Heterogeneity was defined as low, moderate, and high to I 2 values of 25%, 50%, and 75%, respectively [20]. The Begg rank correlation [21] and Egger weighted regression

Study selection
In total, 1221 studies through the initial searches in different datasets as potentially  Table 1 and Supplementary Table 2.

Quality assessment of studies
Newcastle-Ottawa Scales for the eligible studies were presented in Supplementary Table   3 and all included studies were found to exhibit a higher quality. Four studies were evaluated as 6 stars, 6 studies were 7 stars, and 2 studies were 8 stars.

The association between sarcopenia and hypertension
All of theeight eligible studiesreported the ORs of hypertension, and the ORs ranged from 0.41 to 4.38. When pooled the ORs together, the summarized ORs was 1.29 (95% CI=1.00-1.67, P=0.04) with a moderate heterogeneity (I 2 = 74%). The detailed information could be found in Figure 2 and Supplementary Figure 1.
To explore the sources of heterogeneity, subgroup analysis was performed by categorizing the studies according to the ethnicity of the participants and the Newcastle-Ottawa Scales than were equal to or more than 7 stars.The Asian group included 4 studies from China and Korea, the Caucasian group included four studies conducted in United States, Italy, Spain, and Turkey.The summarized ORs for the Asian group 1.50 (95% CI=1.35-1.67, P=0.00) was significantly higher than that of Caucasian group1.08 (95% CI=0.39-2.97, P=0.88).The heterogeneities for the two subgroups were significantly decreased to I 2 = 34% and I 2 =40%.When removed the studies that with lower quality (Newcastle-Ottawa Scales<6), the overall OR were 1.53 (95%CI=1.37-1.71, P=0.00) with lower heterogeneity (I 2 =2.62%). More data was presented in Figure 3 and Figure 4.

The association between handgrip strength and hypertension
8 Eleven studies provided the data on association between handgrip strength and hypertension. Ten studies reported the odds ratios and 95% CI. The overall odds ratios and 95% CIwas 0.99 (95% CI=0.80-1.23, P=0.93) with a higher heterogeneity (I 2 = 76%) and significant public bias (P<0.01). The detailed data can be found in Figure 5. Figure 6 and

Publication bias
Most of the analysis except one was found potential publication bias among the included trials according to Begg rank correlation analysis and Egger weighted regression analysis (P value of the analysis was more than 0.05). For the analysis with public bias, when grouped the studies by the gender of the participants, the public bias was disappeared (P>0.05, Figure 6 and Figure 7). The detailed potential publication bias of each analysis can be found in Supplementary Table 4 Discussion 9 To the best of our knowledge, the current meta-analysis is the first study systematic review and meta-analysis summarized the association between sarcopenia, handgrip strength, and hypertension. 19 studies with 21301 participants were included in the study.
Eight studies addressed the association between sarcopenia and hypertension and indicated that sarcopenia was a risk factor for the hypertension. 11 studies focused on the association between handgrip strength and hypertension and no association was found by the pooled results.
Being limited by lacking a standard definition for the sarcopenic, the current study proved sarcopenic was a risk factor for hypertension. Several prospective and cross-sectional studies have found the link between sarcopenic and hypertension [8,17].The prevalence of sarcopenic can vary dramatically depend depending on the definition of sarcopenic obesity. In the current study, Asian Working Group for Sarcopenia (AWGS) criteria and the European Working Group on Sarcopenia in Older People (EWGSOP) criteria were used and the odds ratios were slightly different. This might partly explain Asian groups had a stronger association with hypertension than that ofCaucasian group. Precious study [32] observed that obesity or sarcopenia, or both might be the initiation of sarcopenic. The obesity is caused by the surplus of energy intake relative to energy expenditure. Therefore, sarcopenia may result from a discrepancy in anabolism and catabolism of skeletal muscle protein [33].
In the current study, handgrip strength was negatively associated with hypertension in both men and women. The result was controversial in various studies [24,25]. The specific biological mechanism linking grip strength and sarcopenia with hypertension is keeping unknown. However, of note, regular exercise, which has been shown consistently in plenty of studies to improve the blood pressure, may improve mitochondrial function and reducing inflammation and result in improving metabolic function and decrease sarcopenia [34].
It is necessary to consider the limitations of the present meta-analysis while interpreting the results. First, the definition of sarcopenia inconsistent in different studies and the variations in assessment of sarcopenia across studies could have caused methodological limitations and compromised the results. Second, the number of the included studies was limited and majority of them were from Asian countries. As the sarcopenia might be affected by the economic level, medical level, and genetic factors, the associations betweensarcopenia, handgrip strength, and hypertension in different countries could be slightly different. Therefore, the result in the current can only partly annotate the associations. Three, almost all of studies addressing the sarcopenia did not provided the specific sarcopenia by gender and age. Due to the limited sample size of each studies, we cannot perform more subgroups or sensitivity analyses.Therefore, due to the limited information, we cannot perform more subgroups or sensitivity analyses, especially on the sensitivity analyses on age and sex. Four, potential language bias might exist because our literature searches only considered articles published in English.

Conclusions
In conclusion, our meta-analysis provided pooled results based 19 studies from eight different regions or countries, and summarized a large data set of 21301 participants. The current study highlighted that sarcopenia was associated with hypertension. In the future, by stratifying patients, efforts must be made to prevent and treat sarcopenia in the older population, which would also decrease the risk of hypertension and the comorbidities of

Competing interests
The authors declare that they have no competing interests     Summarized overall odds ratio of hypertension of the studies that with equal to or more than 7 stars of the Newcastle-Ottawa Scales     Summarized overall odds ratio of handgrip strength based on female participants