Growing evidence indicates that peripheral neuropathy (PN) is common even in the absence of diabetes
However, the clinical sequelae of PN have not been quantified in the general population.
To assess ...the associations of PN with all-cause and cardiovascular mortality in the general adult population of the United States.
Prospective cohort study.
NHANES (National Health and Nutrition Examination Survey), 1999 to 2004.
7116 adults aged 40 years or older who had standardized monofilament testing for PN.
Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality after adjustment for demographic and cardiovascular risk factors, overall and stratified by diabetes status.
The overall prevalence of PN (±SE) was 13.5% ± 0.5% (27.0% ± 1.4% in adults with diabetes and 11.6% ± 0.5% in adults without diabetes). During a median follow-up of 13 years, 2128 participants died, including 488 of cardiovascular causes. Incidence rates (per 1000 person-years) of all-cause mortality were 57.6 (95% CI, 48.4 to 68.7) in adults with diabetes and PN, 34.3 (CI, 30.3 to 38.8) in adults with PN but no diabetes, 27.1 (CI, 23.4 to 31.5) in adults with diabetes but no PN, and 13.0 (CI, 12.1 to 14.0) in adults with no diabetes and no PN. In adjusted models, PN was significantly associated with all-cause mortality (hazard ratio HR, 1.49 CI, 1.15 to 1.94) and cardiovascular mortality (HR, 1.66 CI, 1.07 to 2.57) in participants with diabetes. In those without diabetes, PN was significantly associated with all-cause mortality (HR, 1.31 CI, 1.15 to 1.50), but the association between PN and cardiovascular mortality was not statistically significant after adjustment (HR, 1.27 CI, 0.98 to 1.66).
Prevalent cardiovascular disease was self-reported, and PN was defined by monofilament testing only.
Peripheral neuropathy was common and was independently associated with mortality in the U.S. population, even in the absence of diabetes. These findings suggest that decreased sensation in the foot may be an underrecognized risk factor for death in the general population.
National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute of the National Institutes of Health.
Dementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden ...of disease. We investigated whether specific AHM classes reduced the risk for dementia.
We did a meta-analysis of individual participant data from eligible observational studies published between Jan 1, 1980, and Jan 1, 2019. Cohorts were eligible for inclusion if they prospectively recruited community-dwelling adults; included more than 2000 participants; collected data for dementia events over at least 5 years; had measured blood pressure and verified use of AHMs; included in-person exams, supplemented with additional data, to capture dementia events; and had followed up cases for mortality. We assessed the association of incident dementia and clinical Alzheimer's disease with use of five AHM classes, within strata of baseline high (systolic blood pressure SBP ≥140 mm Hg or diastolic blood pressure DBP ≥90 mm Hg) and normal (SBP <140 mm Hg and DBP <90 mm Hg) blood pressure. We used a propensity score to control for confounding factors related to the probability of receiving AHM. Study-specific effect estimates were pooled using random-effects meta-analyses.
Six prospective community-based studies (n=31 090 well phenotyped dementia-free adults older than 55 years) with median follow-ups across cohorts of 7–22 years were eligible for analysis. There were 3728 incident cases of dementia and 1741 incident Alzheimer's disease diagnoses. In the high blood pressure stratum (n=15 537), those using any AHM had a reduced risk for developing dementia (hazard ratio HR 0·88, 95% CI 0·79–0·98; p=0·019) and Alzheimer's disease (HR 0·84, 0·73–0·97; p=0·021) compared with those not using AHM. We did not find any significant differences between one drug class versus all others on risk of dementia. In the normal blood pressure stratum (n=15 553), there was no association between AHM use and incident dementia or Alzheimer's disease.
Over a long period of observation, no evidence was found that a specific AHM drug class was more effective than others in lowering risk of dementia. Among people with hypertensive levels of blood pressure, use of any AHM with efficacy to lower blood pressure might reduce the risk for dementia. These findings suggest future clinical guidelines for hypertension management should also consider the beneficial effect of AHM on the risk for dementia.
The Alzheimer's Drug Discovery Foundation and the National Institute on Aging Intramural Research Program.
Peripheral neuropathy is associated with substantial morbidity, but risk factors other than diabetes are largely uncharacterized. The aim of this study was to describe the prevalence and risk factors ...for peripheral neuropathy in adults with and without diabetes from two different population-based studies in the US. We performed a cross-sectional analysis of 5200 black and white participants from NHANES (1999-2004, age 40-85 years) and 3362 black and white participants from the ARIC Study (2016-2017, age 70-89 years) who underwent monofilament testing for peripheral neuropathy using a shared protocol. We used logistic regression to quantify age, sex, and race-adjusted risk factor associations for peripheral neuropathy among middle-aged (40-69 years) and older (≥ 70 years) adults. The age, sex, and race-adjusted prevalence of peripheral neuropathy (decreased sensation on monofilament testing) was 10.4% for middle-aged adults in NHANES, 26.8% for older adults in NHANES, and 39.2% for older adults in ARIC. Diabetes was an important risk factor, but more strongly associated with peripheral neuropathy in middle-aged (OR ~ 5 for long-standing diabetes) compared to older adults (ORs ~ 1.5-2). Male sex (ORs ~ 2), black race (ORs ~ 1.3-1.5), and greater height (ORs ~ 1.5-3) were robust risk factors for peripheral neuropathy. Other risk factors included body mass index, education, and peripheral artery disease. The burden of peripheral neuropathy defined by abnormal monofilament testing among older adults is substantial, even among adults without diabetes. Studies are needed to understand the etiology and prognosis of peripheral neuropathy in the absence of diabetes.
IMPORTANCE: Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. ...OBJECTIVES: To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. MAIN OUTCOMES AND MEASURES: Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status–Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. RESULTS: In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean SD age at visit 1 of 57.4 5.2 years) were identified among 15 744 participants. Black race (hazard ratio HR, 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype. CONCLUSIONS AND RELEVANCE: Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.
Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice ...and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Predictors Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr ) and serum cystatin C level (eGFRcys ) and urine albumin-creatinine ratio. Outcome Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results 341 (7%) participants were classified as frail, 1,475 (30%) had eGFRcr < 60 mL/min/1.73 m2 , 2,480 (50%) had eGFRcys < 60 mL/min/1.73 m2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys < 60 mL/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and albumin-creatinine ratio. Frail individuals with eGFRcr of 60 to <75 mL/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to <30 mL/min/1.73 m2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.
Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. ...Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.
To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age approximately 70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.
Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes in older age is heterogeneous, and the treatment approach varies by patient characteristics. We characterized the short-term all-cause and cardiovascular mortality risk associated with ...hyperglycemia in older age.
We included 5,791 older adults in the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013; ages 66-90 years). We compared prediabetes (HbA
5.7% to <6.5%), newly diagnosed diabetes (HbA
≥6.5%, prior diagnosis <1 year, or taking antihyperglycemic medications <1 year), short-duration diabetes (duration ≥1 year but <10 years median), and long-standing diabetes (duration ≥10 years). Outcomes were all-cause and cardiovascular mortality (median follow-up of 5.6 years).
Participants were 58% female, and 24% had prevalent cardiovascular disease. All-cause mortality rates, per 1,000 person-years, were 21.2 (95% CI 18.7, 24.1) among those without diabetes, 23.7 (95% CI 20.8, 27.1) for those with prediabetes, 33.8 (95% CI 25.2, 45.5) among those with recently diagnosed diabetes, 29.6 (95% CI 25.0, 35.1) for those with diabetes of short duration, and 48.6 (95% CI 42.4, 55.7) for those with long-standing diabetes. Cardiovascular mortality rates, per 1,000 person-years, were 5.8 (95% CI 4.6, 7.4) among those without diabetes, 6.6 (95% CI 5.2, 8.5) for those with prediabetes, 11.5 (95% CI 7.0, 19.1) among those with recently diagnosed diabetes, 8.2 (95% CI 5.9, 11.3) for those with diabetes of short duration, and 17.3 (95% CI 13.8, 21.7) for those with long-standing diabetes. After adjustment for other cardiovascular risk factors, prediabetes and newly diagnosed diabetes were not significantly associated with a higher risk of all-cause mortality (hazard ratio HR 1.03 95% CI 0.85, 1.23 and HR 1.31 95% CI 0.94, 1.82, respectively) or cardiovascular mortality (HR 1.00 95% CI 0.70, 1.43 and HR 1.35 95% CI 0.74, 2.49, respectively). Excess mortality risk was primarily concentrated among those with long-standing diabetes (all-cause: HR 1.71 95% CI 1.40, 2.10; cardiovascular: HR 1.72 95% CI 1.18, 2.51).
In older adults, long-standing diabetes has a substantial and independent effect on short-term mortality. Older individuals with prediabetes remained at low mortality risk over a median 5.6 years of follow-up.
Incorporation of comorbidity burden to inform diabetes management in older adults remains challenging. High-sensitivity cardiac troponins are objective, quantifiable biomarkers that may improve risk ...monitoring in older adults. We assessed the associations of elevations in high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) with comorbidities and improvements in mortality risk stratification.
We used logistic regression to examine associations of comorbidities with elevations in either troponin (≥85th percentile) among 1,835 participants in the Atherosclerosis Risk in Communities (ARIC) Study with diabetes (ages 67-89 years, 43% male, 31% black) at visit 5 (2011-2013). We used Cox models to compare associations of high cardiac troponins with mortality across comorbidity levels.
Elevations in either troponin (≥9.4 ng/L for hs-cTnI, ≥25 ng/L for hs-cTnT) were associated with prevalent coronary heart disease, heart failure, chronic kidney disease, pulmonary disease, hypoglycemia, hypertension, dementia, and frailty. Over a median follow-up of 6.2 years (418 deaths), both high hs-cTnI and high hs-cTnT further stratified mortality risk beyond comorbidity levels; those with a high hs-cTnI or hs-cTnT and high comorbidity were at highest mortality risk. Even among those with low comorbidity, a high hs-cTnI (hazard ratio 3.0 95% CI 1.7, 5.4) or hs-cTnT (hazard ratio 3.3 95% CI 1.8, 6.2) was associated with elevated mortality.
Many comorbidities were reflected by both hs-cTnI and hs-cTnT; elevations in either of the troponins were associated with higher mortality risk beyond comorbidity burden. High-sensitivity cardiac troponins may identify older adults at high mortality risk and be useful in guiding clinical care of older adults with diabetes.
Long-chain sphingomyelins (SMs) may play an important role in the stability of myelin sheath underlying physical function. The objective of this study was to examine the cross-sectional and ...longitudinal associations of long-chain SMs SM (41:1), SM (41:2), SM (43:1) and ceramides Cer (41:1) and Cer (43:1) with physical function in the Atherosclerosis Risk in Communities (ARIC) study. Plasma concentrations of SM (41:1), SM (41:2), SM (43:1), Cer (41:1) and Cer (43:1) were measured in 389 ARIC participants in 2011-13. Physical function was assessed by grip strength, Short Physical Performance Battery (SPPB), 4-m walking speed at both 2011-13 and 2016-17, and the modified Rosow-Breslau questionnaire in 2016-2017. Multivariable linear and logistic regression analyses were performed, controlling for demographic and clinical confounders. In cross-sectional analyses, plasma concentrations of SM 41:1 were positively associated with SPPB score (β-coefficients 95% confidence internal: 0.33 0.02, 0.63 per 1 standard deviation SD increase in log-transformed concentration, p value 0.04), 4-m walking speed (0.042 m/s 0.01, 0.07, p value 0.003), and negatively with self-reported disability (odds ratio = 0.73 0.65, 0.82, p value < 0.0001). Plasma concentrations of the five metabolites examined were not significantly associated with longitudinal changes in physical function or incidence of poor mobility. In older adults, plasma concentrations of long-chain SM 41:1 were cross-sectionally positively associated with physical function.
Peripheral neuropathy and erectile dysfunction are common conditions that have both been linked to cardiovascular disease and its risk factors, especially diabetes. The aim of this study was to ...assess the association of large-fiber peripheral neuropathy with erectile dysfunction in adult US males with and without diabetes.
We included all men aged ≥40 years from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) with data on erectile dysfunction and peripheral neuropathy (n = 1213, including 206 men with diabetes). Erectile dysfunction was assessed by a single question during a self-paced, computer-assisted self-interview. Peripheral neuropathy was evaluated using standardized 10-g monofilament testing, which assesses lower extremity sensation. We used logistic regression to examine the association of peripheral neuropathy with erectile dysfunction overall and stratified by diabetes status, adjusting for demographic and cardiovascular risk factors.
The prevalence of peripheral neuropathy was 26.1% (51.2% in men with diabetes and 22.5% in men without diabetes). There was a significant independent association of peripheral neuropathy with erectile dysfunction overall (odds ratio OR 1.71, 95% confidence interval CI, 1.20-2.43) and among US adult men without diabetes (OR 1.68; 95% CI, 1.11-2.56). The association in adults with diabetes was not statistically significant (OR 1.29; 95% CI, 0.39-4.26), possibly owing to limited power in this subgroup.
Our study suggests that decreased lower extremity sensation, even in the absence of diabetes, is common and a novel risk factor for erectile dysfunction.
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