Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

Background and objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Association between cardiovascular risk and coronavirus disease 2019: findings from 2021 National Health Interview Survey.

PURPOSE: To examine the association between pre-existing cardiovascular disorders and the risk of coronavirus disease 2019 (COVID-19) among community-dwelling adults in the United States. METHODS: We analyzed data from the 2021 National Health Interview Survey, encompassing 28,848 nationally representative participants aged ≥18. We examined the association by two age groups, younger adults (aged 18-59) and older adults (aged ≥60). Weighted analyses were conducted to consider the complex sampling design used in the National Health Interview Survey. RESULTS: The results show that 13.9% of younger and 8.2% of older adults were infected with coronavirus, corresponding to a nationwide estimate of 23,701,358 COVID-19 cases in younger adults and 6310,206 in older adults in 2021. Pre-existing cardiovascular risk factors (overweight, obesity, hypertension, and diabetes) in both age groups and pre-existing cardiovascular diseases (angina, heart attack, and coronary heart disease) in older adults were significantly associated with COVID-19 infection. Significant dose-response relationships existed between increased pre-existing cardiovascular risk factors and COVID-19 infection, with the strongest association in non-Hispanic Black, followed by Hispanic ethnicities and non-Hispanic White. CONCLUSIONS: Pre-existing cardiovascular disorders are significantly associated with the risk of COVID-19 infection. The magnitudes of this risk association are more substantial among minority populations.

Vitamin d deficiency and metabolic syndrome: The joint effect on cardiovascular and all-cause mortality in the United States adults.

BACKGROUND: The long-term impact of vitamin D deficiency and metabolic syndrome (MetS) on cardiovascular disease (CVD) and all-cause mortality are still a matter of debate. AIM: To test the hypotheses that lower serum 25 hydroxyvitamin D [25(OH)D] concentrations (a marker of vitamin D level) and MetS have a long-term impact on the risk of CVD and all-cause mortality, and individuals with vitamin D deficiency can be identified by multiple factors. METHODS: A sample of 9094 adults, 20 to 90 years of age, who participated in the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994) were followed through December 2015 was analyzed. The associations of serum 25(OH)D concentrations and MetS with CVD and all-cause mortality were analyzed longitudinally using Cox regression models. Classification and regression tree (CART) for machine learning was applied to classify individuals with vitamin D deficiency. RESULTS: Of 9094 participants, 30% had serum 25(OH)D concentrations < 20 ng/mL (defined as vitamin D deficiency), 39% had serum 25(OH)D concentrations between 20 to 29 ng/mL (insufficiency), and 31% had serum 25(OH)D concentrations ≥30 ng/mL (sufficiency). Prevalence of MetS was 28.4%. During a mean of 18 years follow-up, vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. Subjects with both vitamin D deficiency and MetS had the highest risk of CVD mortality (HR = 1.77, 95%CI: 1.22-2.58) and all-cause mortality (HR = 1.62, 95%CI: 1.26-2.09), followed by those with both vitamin D insufficiency and MetS for CVD mortality (HR = 1.59, 95%CI: 1.12-2.24), and all-cause mortality (HR = 1.41, 95%CI: 1.08-1.85). Meanwhile, vitamin D sufficiency significantly decreased the risk of CVD and all-cause mortality for those who even had MetS. Among the total study sample, CART analysis suggests that being non-Hispanic Black, having lower serum folate level, and being female were the first three predictors for those with serum 25(OH)D deficiency. CONCLUSION: Vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. There was a significant joint effect of vitamin D deficiency and MetS on the risk of mortality. Findings of the CART analysis may be useful to identify individuals positioned to benefit from interventions to reduce the risk of CVD and all-cause mortality.

Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the Women's Health Initiative Memory Study.

BACKGROUND: Whether blood pressure (BP), and at what level of controlled BP, reduces risk of cognitive impairment remains uncertain. We investigated the association of BP and hypertension treatment status with mild cognitive impairment and dementia in older women. METHODS: We prospectively analysed a sample of 7207 community-dwelling women aged 65-79 years participating in the Women's Health Initiative Memory Study (WHIMS). Participants were recruited between May 28, 1996, and Dec 13, 1999, at 39 US clinical centres, and they were followed up until Dec 31, 2019. Cognitive function was assessed annually. Mild cognitive impairment and probable dementia were defined through a centralised adjudication process. BP was measured by trained and certified staff at baseline. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Hypertension was defined using the American Heart Association 2017 Guideline for High BP in Adults. Outcomes were (1) mild cognitive impairment, (2) probable dementia, and (3) cognitive loss (the combined endpoint of either mild cognitive impairment or probable dementia, or both). We estimated hazard ratios (HRs) to assess the association between hypertension, SBP, and PP with the risk of study outcomes using Cox proportional hazards regression models, with adjustment for key covariates. FINDINGS: During a median follow-up of 9 years (IQR 6-15), 1132 (15·7%) participants were classified as mild cognitive impairment, 739 (10·3%) as probable dementia, and 1533 (21·3%) as cognitive loss. The incidence rates per 1000 person-years were 15·3 cases (95% CI 14·4-16·2) for mild cognitive impairment, 9·7 cases (9·0-10·4) for probable dementia, and 20·3 (19·3-21·3) for cognitive loss. Elevated SBP and PP were significantly associated with increased risk of mild cognitive impairment and cognitive loss (test for trends across SBP and PP strata, p<0·01). Individuals with hypertension, but with controlled SBP of less than 120 mm Hg did not have a significantly increased risk of mild cognitive impairment (HR 1·33, 95% CI 0·98-1·82, p=0·071), and of cognitive loss (1·09, 0·82-1·44, p=0·57) compared with normotension. Individuals on anti-hypertensive treatment with PP of less than 50 mm Hg did not have a significantly higher risk of mild cognitive impairment (1·26, 0·98-1·62, p=0·07) and of cognitive loss (1·17, 0·94-1·46, p=0·16). There were no significant associations between hypertension, SBP, or PP and probable dementia. INTERPRETATION: Results of our study show significant associations of hypertension and elevated SBP and PP levels with risk of mild cognitive impairment and the combined endpoint of either mild cognitive impairment or probable dementia, suggesting that intensive control of hypertension, SBP, and PP can preserve cognitive health in older women. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services.