Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis.

Background: The role of certain biomarkers in the development of single cardiometabolic disease (CMD) has been intensively investigated. Less is known about the association of biomarkers with multiple CMDs (cardiometabolic multimorbidity, CMM), which is essential for the exploration of molecular targets for the prevention and treatment of CMM. We aimed to systematically synthesize the current evidence on CMM-related biomarkers. Methods: We searched PubMed, Embase, Web of Science, and Ebsco for relevant studies from inception until August 31st, 2022. Studies reported the association of serum/plasma biomarkers with CMM, and relevant effect sizes were included. The outcomes were five progression patterns of CMM: (1) no CMD to CMM; (2) type 2 diabetes mellitus (T2DM) followed by stroke; (3) T2DM followed by coronary heart disease (CHD); (4) T2DM followed by stroke or CHD; and (5) CHD followed by T2DM. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the included studies. A meta-analysis was conducted to quantify the association of biomarkers and CMM. Results: A total of 68 biomarkers were identified from 42 studies, which could be categorized into five groups: lipid metabolism, glycometabolism, liver function, immunity, and others. Lipid metabolism biomarkers were most reported to associate with CMM, including TC, TGs, HDL-C, LDL-C, and Lp(a). Fasting plasma glucose was also reported by several studies, and it was particularly associated with coexisting T2DM with vascular diseases. According to the quantitative meta-analysis, HDL-C was negatively associated with CHD risk among patients with T2DM (pooled OR for per 1 mmol/L increase = 0.79, 95% CI = 0.77-0.82), whereas a higher TGs level (pooled OR for higher than 150 mg/dL = 1.39, 95% CI = 1.10-1.75) was positively associated with CHD risk among female patients with T2DM. Conclusion: Certain serum/plasma biomarkers were associated with the progression of CMM, in particular for those related to lipid metabolism, but heterogeneity and inconsistent findings still existed among included studies. There is a need for future research to explore more relevant biomarkers associated with the occurrence and progression of CMM, targeted at which is important for the early identification and prevention of CMM.

Socioeconomic inequalities in physical, psychological, and cognitive multimorbidity in middle-aged and older adults in 33 countries: a cross-sectional study.

BACKGROUND: Many physical, psychological, and cognitive disorders are highly clustered among populations with low socioeconomic status. However, the extent to which socioeconomic status is associated with different combinations of these disorders is unclear, particularly outside high-income countries. We aimed to evaluate these associations in 33 countries including high-income countries, upper-middle-income countries, and one lower-middle-income country. METHODS: This cross-sectional multi-region study pooled individual-level data from seven studies on ageing between 2017 and 2020. Education and total household wealth were used to measure socioeconomic status. Physical disorder was defined as having one or more of the self-reported chronic conditions. Psychological and cognitive disorders were measured by study-specific instruments. The outcome included eight categories: no disorders, physical disorder, psychological disorder, cognitive disorder, and their four combinations. Multivariable-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% CIs for the associations of socioeconomic status with these outcomes separately for high-income countries, upper-middle-income countries, and the lower-middle-income country. FINDINGS: Among 167 376 individuals aged 45 years and older, the prevalence of multimorbidity was 24·5% in high-income countries, 33·9% in upper-middle-income countries, and 8·1% in the lower-middle-income country (India). Lower levels of education, household wealth, and a combined socioeconomic status score were strongly associated with physical, psychological, and cognitive multimorbidity in high-income countries and upper-middle-income countries, with ORs (low vs high socioeconomic status) for physical-psychological-cognitive multimorbidity of 12·36 (95% CI 10·29-14·85; p<0·0001) in high-income countries and of 23·84 (18·85-30·14; p<0·0001) in upper-middle-income countries. The associations in the lower-middle-income country were mixed. Participants with both a low level of education and low household wealth had the highest odds of multimorbidity (eg, OR for physical-psychological-cognitive multimorbidity 21·21 [15·95-28·19; p<0·0001] in high-income countries, 37·07 [25·66-53·56; p<0·0001] in upper-middle-income countries, and 54·96 [7·66-394·38; p<0·0001] in the lower-middle-income country). INTERPRETATION: In study populations from high-income countries, upper-middle-income countries, and the lower-middle-income country, the odds of multimorbidity, which included physical, psychological, and cognitive disorders, were more than ten times greater in individuals with low socioeconomic status. Equity-oriented policies and programmes that reduce social inequalities in multimorbidity are urgently needed to achieve Sustainable Development Goals. FUNDING: Zhejiang University, Fundamental Research Funds for the Central Universities, The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Wellcome Trust, Medical Research Council, National Institute on Aging, and Academy of Finland. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Immunization coverage, knowledge, satisfaction, and associated factors of non-National Immunization Program vaccines among migrant and left-behind families in China: evidence from Zhejiang and Henan provinces.

BACKGROUND: Migrant and left-behind families are vulnerable in health services utilization, but little is known about their disparities in immunization of non-National Immunization Program (NIP) vaccines. This study aims to evaluate the immunization coverage, knowledge, satisfaction, and associated factors of non-NIP vaccines among local and migrant families in the urban areas and non-left-behind and left-behind families in the rural areas of China. METHODS: A cross-sectional survey was conducted in urban areas of Zhejiang and rural areas of Henan in China. A total of 1648 caregivers of children aged 1-6 years were interviewed face-to-face by a pre-designed online questionnaire, and their families were grouped into four types: local urban, migrant, non-left-behind, and left-behind. Non-NIP vaccines included Hemophilus influenza b (Hib) vaccine, varicella vaccine, rotavirus vaccine, enterovirus 71 vaccine (EV71) and 13-valent pneumonia vaccine (PCV13). Log-binomial regression models were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the difference on immunization coverage of children, and knowledge and satisfaction of caregivers among families. The network models were conducted to explore the interplay of immunization coverage, knowledge, and satisfaction. Logistic regression models with odds ratios (ORs) and 95% CIs were used to estimate the associated factors of non-NIP vaccination. RESULTS: The immunization coverage of all non-NIP vaccines and knowledge of all items of local urban families was the highest, followed by migrant, non-left-behind and left-behind families. Compared with local urban children, the PRs (95% CIs) for getting all vaccinated were 0.65 (0.52-0.81), 0.29 (0.22-0.37) and 0.14 (0.09-0.21) among migrant children, non-left-behind children and left-behind children, respectively. The coverage-knowledge-satisfaction network model showed the core node was the satisfaction of vaccination schedule. Non-NIP vaccination was associated with characteristics of both children and caregivers, including age of children (> 2 years-OR: 1.69, 95% CI: 1.07-2.68 for local urban children; 2.67, 1.39-5.13 for migrant children; 3.09, 1.23-7.76 for non-left-behind children); and below caregivers' characteristics: family role (parents: 0.37, 0.14-0.99 for non-left-behind children), age (≤ 35 years: 7.27, 1.39-37.94 for non-left-behind children), sex (female: 0.49, 0.30-0.81 for local urban children; 0.31, 0.15-0.62 for non-left-behind children), physical health (more than average: 1.58, 1.07-2.35 for local urban children) and non-NIP vaccines knowledge (good: 0.45, 0.30-0.68 for local urban children; 7.54, 2.64-21.50 for left-behind children). CONCLUSIONS: There were immunization disparities in non-NIP vaccines among migrant and left-behind families compared with their local counterparts. Non-NIP vaccination promotion strategies, including education on caregivers, and optimization of the immunization information system, should be delivered particularly among left-behind and migrant families.

The association between depression during perimenopause and progression of chronic conditions and multimorbidity: results from a Chinese prospective cohort.

PURPOSE: The association between perimenopausal depression and many chronic conditions among women has been well-established. However, the role of depression during perimenopause in the progression of multiple chronic conditions (multimorbidity) remains poorly understood. MATERIAL AND METHODS: A total of 1,216 community-dwelling women in their perimenopause period between 2010 and 2016 were enrolled in our analysis, and followed up for the progression of multimorbidity. Depression, as well as its severity, was evaluated by the Center for Epidemiologic Studies Depression 10-item scale (CES-D-10). Progression of multimorbidity was defined as the first report of two or more chronic conditions for participants without multimorbidity or the new report of one or more conditions for those with multimorbidity. Univariable and multivariable Cox proportional hazards model and the restricted cubic spline regression model were performed to assess the prospective association between perimenopausal depression and the progression of multimorbidity. RESULTS: A total of 480 (39.5%) women reported depression during perimenopause, and 529 (43.5%) women progressed to multimorbidity. After adjusting for socio-demographic and lifestyle factors, perimenopausal depression was independently associated with the progression of multimorbidity (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.13 to 1.60). Moreover, the severity of depression was positively and linearly associated with the progression of multimorbidity (P < 0.05). CONCLUSIONS: Our finding reveals a prospective association between perimenopausal depression and the progression of multimorbidity, indicating interventions targeting perimenopausal depression may reduce the burden of chronic diseases and multimorbidity in women's post-menopausal life.

Association of birth and childhood weight with risk of chronic diseases and multimorbidity in adulthood.

BACKGROUND: Little is known about the relationship between early life body size and occurrence of life-course multiple chronic diseases (multimorbidity). We aim to evaluate associations of birth weight, childhood body size, and their changes with the risks of chronic diseases and multimorbidity. METHODS: This prospective cohort study included 246,495 UK Biobank participants (aged 40-69 years) who reported birth weight and childhood body size at 10 years old. Birth weight was categorized into low, normal, and high; childhood body size was reported as being thinner, average, or plumper. Multimorbidity was defined as having two or more of 38 chronic conditions retrieved from inpatient hospital data until 31 December, 2020. The Cox regression and quasi-Poisson mixed effects models were used to estimate the associations. RESULTS: We show that 57,071 (23.2%) participants develop multimorbidity. Low birth weight (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.26-1.33), high birth weight (HR 1.02, 95% CI > 1.00-1.05), thinner (HR 1.21, 95% CI 1.18-1.23) and plumper body size (HR 1.06, 95% CI 1.04-1.09) are associated with higher risks of multimorbidity. A U-shaped relationship between birth weight and multimorbidity is observed. Changing to be thinner or plumper is associated with multimorbidity and many conditions, compared to changing to be average. CONCLUSIONS: Low birth weight, being thinner and changing to have a thinner body size in childhood are associated with higher risks of developing multimorbidity and many chronic conditions in adulthood. Early monitoring and maintaining a normal body size in childhood could have life-course benefits for preventing multimorbidity above and beyond individual conditions.

Little is known about the relationship between childhood body size and the risk of developing more than one chronic disease later in life. Using data from the UK, we found that low birth weight, high birth weight, and being thinner or plumper than average during childhood were all associated with higher risks of developing more than one chronic disease in adulthood. In addition, changing body shape during childhood to be either thinner or plumper, was associated with being more likely to develop more than one chronic disease later in life. Our results highlight the importance of early monitoring and maintenance of average body size in childhood, as this might prevent the occurrence of chronic diseases later in life.

Sleep Problems Associate With Multimorbidity: A Systematic Review and Meta-analysis.

Objectives: To summarize the evidence on the association between sleep problems and multimorbidity. Methods: Six electronic databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, VIP, and Wan fang) were searched to identify observational studies on the association between sleep problems and multimorbidity. A random-effects model was used to estimate the pooled odds ratios (ORs) and 95% confidence intervals for multimorbidity. Results: A total of 17 observational studies of 133,575 participants were included. Sleep problems included abnormal sleep duration, insomnia, snoring, poor sleep quality, obstructive sleep apnea (OSA) and restless legs syndrome (RLS). The pooled ORs (95% CIs) for multimorbidity were 1.49 (1.24-1.80) of short sleep duration, 1.21 (1.11-1.44) of long sleep duration and 2.53 (1.85-3.46) for insomnia. The association of other sleep problems with multimorbidity was narratively summarized due to limited number of comparable studies. Conclusion: Abnormal sleep duration and insomnia are associated with higher odds of multimorbidity, while the evidence on association of snoring, poor sleep quality, obstructive sleep apnea and restless legs syndrome with multimorbidity remains inconclusive. Interventions targeting sleep problems should be delivered for better management of multimorbidity.

Sleep Behaviors and Progression of Multimorbidity in Middle-Aged and Older Adults: A Prospective Cohort Study From China.

BACKGROUND: Sleep behavior (eg, sleep duration, sleep quality, and nap) is closely related to many chronic conditions. However, less is known about its association with multiple chronic conditions (multimorbidity), particularly evidence from cohort studies. METHODS: Data were collected from a cohort of 8 937 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (2011-2018). Sleep duration, sleep quality, and nap duration were collected in 2011 and 2013. Progression of multimorbidity was defined as the first report of 2 or more chronic conditions for participants without multimorbidity or the new report of 1 or more conditions for those with multimorbidity. Cox regression models were performed to calculate the hazard ratios and 95% confidence intervals (CIs) of the associations between sleep behaviors and the progression of multimorbidity. RESULTS: Short sleep duration and poor sleep quality were associated with the progression of multimorbidity independently and jointly, especially in those less than 65 years and females. The U-shaped dose-response relationships were observed between nighttime and total sleep duration and the progression of multimorbidity. Persistent short and unsteadily changed sleep behaviors increased the risk of multimorbidity progression. Individuals sleeping ≤5 h/night with 5-7 restless days/week had 1.53 times higher risk of multimorbidity progression (95% CI: 1.37-1.71), compared to those sleeping 7-8 h/night with <1 restless day/week. CONCLUSIONS: Short sleep duration and poor sleep quality were independently and jointly associated with a higher risk of multimorbidity progression in a mid-to-older population. Optimal sleep duration and sleep quality should be emphasized in multimorbidity prevention and control.

Interventions and management on multimorbidity: An overview of systematic reviews.

BACKGROUND: Multimorbidity poses an immense burden on the healthcare systems globally, whereas the management strategies and guidelines for multimorbidity are poorly established. We aim to synthesize current evidence on interventions and management of multimorbidity. METHODS: We searched four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews). Systematic reviews (SRs) on interventions or management of multimorbidity were included and evaluated. The methodological quality of each SR was assessed by the AMSTAR-2 tool, and the quality of evidence on the effectiveness of interventions was assessed by the grading of recommendations assessment, development and evaluation (GRADE) system. RESULTS: A total of 30 SRs (464 unique underlying studies) were included, including 20 SRs of interventions and 10 SRs summarizing evidence on management of multimorbidity. Four categories of interventions were identified: patient-level interventions, provider-level interventions, organization-level interventions, and combined interventions (combining the aforementioned two or three- level components). The outcomes were categorized into six types: physical conditions/outcomes, mental conditions/outcomes, psychosocial outcomes/general health, healthcare utilization and costs, patients' behaviors, and care process outcomes. Combined interventions (with patient-level and provider-level components) were more effective in promoting physical conditions/outcomes, while patient-level interventions were more effective in promoting mental conditions/outcomes and psychosocial outcomes/general health. As for healthcare utilization and care process outcomes, organization-level and combined interventions (with organization-level components) were more effective. The challenges in the management of multimorbidity at the patient, provider and organizational levels were also summarized. CONCLUSION: Combined interventions for multimorbidity at different levels would be favored to promote different types of health outcomes. Challenges exist in the management at the patient, provider, and organization levels. Therefore, a holistic and integrated approach of patient-, provider- and organization- level interventions is required to address the challenges and optimize care of patients with multimorbidity.

Multimorbidity burden and developmental trajectory in relation to later-life dementia: A prospective study.

INTRODUCTION: This study assessed the associations of multimorbidity burden and its developmental trajectory with later-life dementia. METHODS: Among 5923 Health and Retirement Study participants, major chronic conditions including hypertension, diabetes mellitus, cancer, lung diseases, heart disease, stroke, psychological disorders, and arthritis were self- or proxy-reported in 1994-2008. Dementia diagnosis was self- or proxy-reported in 2008-2018. We used Cox regression to assess the associations of multimorbidity with incident dementia. RESULTS: During follow-up (median = 8 years), 701 participants developed dementia. Each additional chronic condition in 2008 was related to 15% (confidence interval: 9% to 22%) higher hazard of dementia. Multimorbidity trajectories in 1994-2008 were classified as "rapid growth", "steady growth", "slow growth", and "no new condition" by the group-based trajectory modelling methods. Compared to "no new condition", the "rapid growth" trajectory was related to 32% (3% to 69%) higher dementia risk. CONCLUSIONS: Both multimorbidity burden and its developmental trajectory were prospectively associated with risk of dementia.

Solid Fuel Use and the Progression of Multimorbidity in Middle-Aged Chinese Participants: A Prospective Cohort Study.

Objectives: This study aimed to examine the association of solid fuel use for cooking and heating with the progression of multimorbidity. Methods: A total of 5,437 participants from the China Health and Retirement Longitudinal Study were included. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of the independent and joint effects of solid fuel use for cooking and heating with the progression of multimorbidity. Results: The proportion of participants reporting solid fuel use for both cooking and heating was 59.0% at baseline. Solid fuel use for both cooking and heating was associated with the progression of multimorbidity (adjusted OR: 1.42, 95% CI: 1.19-1.70), compared with clean fuel use for both. Conclusion: Solid fuel use for cooking and heating play an important role in the progression of multimorbidity. Therefore, solid fuel reduction should be considered in developing multimorbidity control and prevention programmes.