Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.

BACKGROUND AND AIMS: Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons. METHODS: We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992-1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998-1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI. RESULTS: Mean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06-2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99-1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69-1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89-1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up. CONCLUSIONS: Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

The Associations of Individual and Subclasses of Nonesterified Fatty Acids With Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.

BACKGROUND: We sought to determine the associations between individual nonesterified fatty acids (NEFAs) and disability and mobility limitation. METHODS: We studied 1 734 participants in the Cardiovascular Health Study (CHS), an ongoing population-based cohort study of community-living older American adults. We measured 35 individual NEFA species in fasting serum samples obtained at the 1996-1997 clinic visit. Using yearly assessments of activities of daily living and self-reported mobility, we identified participants with incident disability or mobility limitation during 15 years of follow-up. Cox proportional hazards regression models were used to determine the associations between per SD increment in the individual NEFAs and incident disability and mobility limitations with adjustment for potential confounding factors. RESULTS: Higher concentrations of total and a broad range of individual NEFA species were associated with risk of disability and mobility limitation (disability: HR per SD of total NEFA [SD = 174.70] = 1.11, 95% CI = 1.04-1.18, p = .001; mobility limitation: HR per SD of total NEFA = 1.09, 95% CI = 1.02-1.16, p = .01). Among individual saturated NEFAs (SFAs), myristic (14:0) and palmitic (16:0) acids were significantly associated with higher risk of both disability and mobility limitations, but longer-chain FAs were not. Most individual monounsaturated (MUFA), n-6 polyunsaturated fatty acids (PUFAs), and trans FAs were positively significantly associated with higher risks of both disability and mobility limitation. In contrast, most n-3 PUFA species were not associated with disability or mobility limitation. CONCLUSIONS: Higher risks of disability and mobility limitation were observed for proinflammatory intermediate-chain SFAs, MUFAs, n-6 PUFAs, and trans FAs. Our findings indicated no significant association for anti-inflammatory n-3 PUFAs.

Dietary Macronutrients and Circulating Nonesterified Fatty Acids: A Secondary Analysis of the OMNI Heart Crossover Trial.

BACKGROUND: Nonesterified fatty acids (NEFAs) play key roles in the pathophysiology of diabetes and cardiovascular disease. OBJECTIVES: We sought to determine whether macronutrient content differences affect NEFA concentrations in a randomized crossover trial. METHODS: Total NEFAs were measured from postintervention specimens of participants in the OMNI Heart trial (Optimal Macronutrient Intake Trial to Prevent Heart Disease). OMNI Heart compared 3 healthful diets to evaluate their effect on systolic blood pressure and serum LDL cholesterol: carbohydrate-rich diet (58% carbohydrate); protein-rich diet (25% protein), about half from plant sources; and a diet rich in unsaturated fatty acids (21% unsaturated fat), predominantly monounsaturated. The trial included 164 participants who consumed the 3 diets, each for 6 wk. Data were analyzed from the 156 participants with unthawed serum available from the week 6 visit for all diet periods. We used ANCOVA and generalized estimating equations (GEEs) to compare serum NEFA concentrations across the 3 diet periods. RESULTS: The mean ± SD age of study participants was 52.9 ± 10.6 y and mean BMI was 30.3 ± 6.1 kg/m2. Fifty-five percent of participants were women and 55% were African American. Comparisons of adjusted mean serum NEFA concentrations after each diet intervention identified no statistically significant differences (58% carbohydrate: 0.144 ± 0.083 mEq/L; 25% protein: 0.143 ± 0.076 mEq/L; 21% unsaturated fat: 0.143 ± 0.084 mEq/L; ANCOVA, P = 0.99). Likewise, we observed no significant serum NEFA concentration difference by diet in adjusted GEE models. In adjusted models, serum NEFA concentrations were positively associated, as anticipated, with female sex and higher BMI. CONCLUSIONS: In this randomized crossover trial, we observed nearly identical serum NEFA concentrations after each of 3 healthful diets, regardless of macronutrient content.

Rare Heterogeneous Adverse Events Associated with mRNA-Based COVID-19 Vaccines: A Systematic Review.

Background: Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. Methods: A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Results: Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. Conclusions: As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.

Antibiotic resistance of Escherichia coli urinary tract infections at a North Carolina community hospital: Comparison of rural and urban community type.

OBJECTIVE: We aimed to identify differences in urinary E. coli resistance rates based on community type of patient residence (rural and urban). METHODS: This cross-sectional study examined antibiotic resistance of E. coli isolates from 12,604 urine specimens at a North Carolina hospital between 2016 and 2018. Using multivariable logistic regression modeling, we investigated the association between resistance and community type, adjusting for patient age, gender, season, and setting of infection onset. Analyses were performed using SAS Version 9.3 (SAS Institute, Cary, NC) at alpha = 0.05. RESULTS: Prevalence of resistance was highest for ampicillin (42.2%), ampicillin-sulbactam (24.7%), ciprofloxacin (21.8%), trimethoprim-sulfamethoxazole (SXT) (21.6%), and levofloxacin (21.4%). Rural compared to urban community type was significantly associated with resistance of E. coli urinary isolates to ciprofloxacin (adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 1.16-1.43, P < .0001), levofloxacin (aOR = 1.28, 95% CI = 1.15-1.42, P < .0001), SXT (aOR = 1.15, 95% CI = 1.04-1.27, P = .01), and nitrofurantoin (aOR = 1.57, 95% CI = 1.13-2.17, P = .01). CONCLUSIONS: Rural community type may influence urinary E. coli resistance to fluoroquinolones, SXT, and nitrofurantoin, indicating the need for antimicrobial stewardship interventions in medically underserved populations.

Nonesterified Fatty Acids and Hospitalizations Among Older Adults: The Cardiovascular Health Study.

BACKGROUND: We sought to determine associations between total serum concentrations of nonesterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of older adults. METHODS: We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/1993 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RRs) of hospitalizations and days hospitalized. RESULTS: We identified 21 339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (hazard ratio [HR] per SD [0.2 mEq/L] = 1.07, 95% confidence interval [CI] = 1.03-1.10, p < .001), number of hospitalizations (RR per SD = 1.04, 95% CI = 1.01-1.07, p = .01), and total number of days hospitalized (RR per SD = 1.06, 95% CI = 1.01-1.10, p = .01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage. CONCLUSIONS: Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.

Non-esterified fatty acids and telomere length in older adults: The Cardiovascular Health Study.

BACKGROUND: Telomeres shorten as organisms age, placing limits on cell proliferation and serving as a marker of biological aging. Non-esterified fatty acids (NEFAs) are a key mediator of age-related metabolic abnormalities. We aimed to determine if NEFAs are associated with telomere length in community-living older adults. MATERIAL AND METHODS: We cross-sectionally studied 1648 participants of the Cardiovascular Health Study (CHS) who underwent concomitant telomere length measurement from a sample of 4715 participants who underwent measurement of circulating total fasting NEFAs in stored specimens from their 1992-3 clinic visit. We used linear regression and inverse probability weighting to model telomere length as a function of NEFAs with adjustment for age, gender, race, clinic, BMI, marital status, smoking status, alcohol intake, diabetes status, years of education, hypertension status, prevalent cardiovascular disease, C-reactive protein, total adiponectin, albumin, fetuin-A, fasting insulin, eGFR, total cholesterol, HDL-cholesterol, triglycerides, and general health status. RESULTS: Higher NEFAs were significantly associated with shorter telomere length, after adjusting for age, gender, race, and clinic site (ß = -0.034; SE = 0.015; P = 0.02). Estimates remained similar in fully adjusted models where each SD of NEFA increment was associated with 0.042 kilobase (kb) pairs shorter telomere length (standard error = 0.016; P = 0.007); for comparison the coefficient for a single year of age in the same model was -0.017. These results were similar in strata of sex, and waist circumference although they tended to be strongest among participants in the youngest tertile of age (ß = -0.079; SE = 0.029; P = 0.01). CONCLUSIONS: In this population-based cohort of community-living elders, we observed a significant inverse association between NEFAs and telomere length. If confirmed, NEFAs may represent a promising target for interventions to slow biological aging.

Non-Esterified Fatty Acids and Risks of Frailty, Disability, and Mobility Limitation in Older Adults: The Cardiovascular Health Study.

BACKGROUND/OBJECTIVES: Non-esterified fatty acids (NEFAs) play central roles in the relationship between adiposity and glucose metabolism, and they have been implicated in the pathogenesis of cardiovascular disease, but few studies have assessed their effects on complex geriatric syndromes like frailty that cross multiple organ systems. We sought to determine the relationships between NEFAs and incident frailty, disability, and mobility limitation in a population-based cohort of older persons. METHODS: We analyzed 4,710 Cardiovascular Health Study (CHS) participants who underwent measurement of circulating total fasting NEFAs in 1992-1993 and were assessed for frailty in 1996-1997 and for disability and mobility limitation annually. We used ordinal logistic regression to model incident frailty, linear regression to model components of frailty, and Cox regression to model disability and mobility limitation in relation to baseline NEFAs. To ensure proportional hazards, we truncated follow-up at 9 years for disability and 6.5 years for mobility limitation. RESULTS: A total of 42 participants became frail and 510 became pre-frail over a 4-year period, and we documented 1,720 cases of disability and 1,225 cases of mobility limitation during follow-up. NEFAs were positively associated in a dose-dependent manner with higher risks of incident frailty, disability, and mobility limitation. The adjusted odds ratios for frailty were 1.37 (95% confidence interval [CI] = 1.01-1.86; P = .04) across extreme tertiles and 1.17 (95% CI = 1.03-1.33; P = .01) per standard deviation increment. The corresponding hazard ratios for incident disability were 1.14 (95% CI = 1.01-1.30; P = .04) and 1.11 (95% CI = 1.06-1.17; P < .0001); those for incident mobility limitation were 1.23 (95% CI = 1.06-1.43; P = .006) and 1.15 (95% CI = 1.08-1.22; P < .0001). Results were largely consistent among both men and women. Among individual components of frailty, NEFAs were significantly associated with self-reported exhaustion (ß = .07; standard error = .03; P = .02). CONCLUSION: Circulating NEFAs are significantly associated with frailty, disability, and mobility limitation among older adults. These results highlight the broad spectrum of adverse health issues associated with NEFA in older adults.

Indwelling medical device use and sepsis risk at a health professional shortage area hospital: Possible interaction with length of hospitalization.

BACKGROUND: We aimed to identify risk factors for sepsis diagnosis and possible interaction with length of hospital stay (LOS) among inpatients at a rural Health Professional Shortage Area hospital. METHODS: This case-control study examined 600 adult patients (300 cases and 300 controls) admitted to a rural health system in North Carolina between 2012 and 2018. Case selection was based on assignment of ICD-9-CM diagnostic codes for sepsis. Controls were patients with a medical diagnosis other than sepsis during the observational period. Logistic regression was used to model sepsis diagnosis as a function of indwelling medical device use and stratified by LOS. RESULTS: Indwelling medical device use preadmission and postadmission were significantly associated with increased risk of sepsis diagnosis among patients with extended hospital stays (LOS ≥ 5 days) (odds ratio [OR] = 5.51; 95% confidence interval [CI] = 1.95-15.62; P = .001 and OR = 3.28; 95% CI = 1.24-8.68; P = .017, respectively). Among patients with LOS <5 days, association with sepsis diagnosis was only significant for indwelling medical device use preadmission (OR = 9.61; 95% CI = 3.68-25.08; P < .0001). CONCLUSIONS: Indwelling medical device use was significantly associated with increased risk of sepsis diagnosis and the risk was higher with longer hospitalization.

Risk factors for sepsis morbidity in a rural hospital population: A case-control study.

BACKGROUND: The aim of the study was to identify risk factors for sepsis morbidity in a rural hospital population. METHODS: We used a case-control study design. Patients included adult admissions to a rural health system between January 1, 2012, and December 31, 2015. Case selection was by electronic medical record search for codes of the ICD-9-CM. Cases were validated against Quick Sequential Organ Failure Assessment criteria. Multiple logistic regression modeling was performed to determine which predefined variables were significantly associated with sepsis diagnosis. RESULTS: A total of 220 patients were studied (110 cases and 110 controls). Cases had an in-hospital mortality of 20% compared with 0% of the controls. Indwelling medical device use during hospitalization (adjusted odds ratio [OR], 3.02; 95% confidence interval [CI], 1.44-6.30; P = .003), coronary heart disease (adjusted OR, 2.59; 95% CI, 1.13-5.97; P = .03), and type of health insurance (adjusted OR, 2.36; 95% CI, 1.13-4.93; P = .02) were independently associated with sepsis diagnosis after adjusting for potential confounders. CONCLUSIONS: This study underscores the need for implementation and maintenance of infection control measures during management of patients with indwelling medical devices at a rural hospital.

Ten-year weight gain is associated with elevated fasting insulin levels and precedes glucose elevation.

BACKGROUND: Numerous studies have examined the relationship between endogenous insulin and weight change with mixed results. This study examined the relationship between fasting insulin levels, insulin resistance (IR), and 10-year weight change by glycaemic stage. METHODS: Using data from the US National Health and Nutrition Examination Survey 2011-2014, 3840 participants were divided into 6 groups based on fasting glucose and fasting insulin levels. Fasting insulin concentrations were dichotomized into <25th percentile (normal) and ≥25th percentile (elevated). Ten-year weight change associated with fasting insulin was assessed by glycaemic stage. RESULTS: Average weight change over a 10-year period was higher in individuals with elevated insulin levels compared to the first quartile (1.40 lbs. vs 11.12 lbs, P < .0001). Across all groups, a 1 µU increase in fasting insulin levels resulted in a 0.52-pound increase in weight (P < .0001). Similarly, an increase in HOMA-IR was associated with increase in weight (1.32 lbs per IR unit, P < .0001). Marginal increases in weight were most pronounced in the normal insulin groups compared to elevated insulin groups and diminished as glycaemic stage progressed. CONCLUSIONS: Elevated fasting insulin level was positively associated with weight gain. The impact of fasting insulin and IR on weight gain preceded hyperglycaemia and diminished as glycaemic stage progressed.

Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study.

CONTEXT: Carboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease. OBJECTIVE: The objective of this study is to investigate the association between sleep-disordered breathing (SDB) - a source of oxidative stress - and CML. MATERIALS AND METHODS: About 1002 participants in the Cardiovascular Health Study (CHS) were studied. RESULTS: Women with SDB had significantly higher CML concentration compared with those without SDB (OR = 1.63, 95%CI = 1.03-2.58, p = 0.04). The association was not significant among men. DISCUSSION: SDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study. CONCLUSION: Accumulation of CML may be an adverse health consequence of SDB.