Creatinine to cystatin C ratio, a biomarker of sarcopenia measures and falls risk in community-dwelling older women

Background The ratio of creatinine to cystatin C (Cr:Cyc) has been proposed as a biomarker of sarcopenia, as greater Cr:Cyc is typically associated with greater muscle mass. We examined the relationship between Cr:Cyc with individual sarcopenia measures, 5 y self-reported falls and 12 y fall-related hospitalizations in a prospective cohort study of 1,118 community-dwelling older women (mean age 75.2 ± 2.7 y). Methods Serum Cr:Cyc, hand grip strength and timed-up-and-go (TUG) performance were assessed at baseline (1998), while dual-energy X-ray absorptiometry (DXA) derived ALM/Height (m) 2 was obtained in a subset of women at baseline and 1 year (n=334). Incident 5 y self-reported falls and 12-year falls-related hospitalizations were considered. Results In a multivariable-adjusted model, women with the lowest Cr:Cyc (Quartile [Q] 1) had 5% (1.0 kg) weaker grip strength, as well as 3.7% (0.22 kg/m 2) and 5.5% (0.031) lower ALM adjusted for height 2 or BMI, respectively, compared to women in Q4 (all p<0.05). 329 women reported an incident fall over 5 years, and 326 fall-related hospitalizations were recorded over 12 years. Women in Q1 of Cr:Cyc had a greater relative hazard for a fall over 5 years (HR 1.50 95%CI 1.11-2.01) and fall-related hospitalization over 12 years (HR 1.53 95%CI 1.13-2.07) compared to Q4 in the multivariable-adjusted model. Conclusion These findings support further investigation into the use of Cr:Cyc as a muscle biomarker to help clinicians identify individuals at risk of falls for early inclusion into evidence-based primary prevention programs targeting improvements to diet and exercise.

Individual and combined association analysis of famine exposure and serum uric acid with hypertension in the mid-aged and older adult: a population-based cross-sectional study

Background Malnutrition in early life may affect health in later life. The associations between malnutrition and serum uric acid (SUA) and hypertension were inconsistent. The present study aimed to investigate the individual and combined association between famine exposure and serum uric acid and hypertension in middle-aged and older Chinese. Methods Data were selected from the China Health and Retirement Longitudinal Study (CHARLS) Wave2011. The analytic sample included 9368 individuals aged 45 to 90. Differences between baseline characteristics and famine exposure/SUA level were evaluated using the Chi-square test, t-test, and F-test. Then, the differences in the prevalence of hypertension between characteristic groups was also estimated by the Chi-square and t-test. Finally, multivariable-adjusted logistic regression models examined association of famine exposure and serum uric acid with odds of prevalence of hypertension. Results A total of 9368 individuals were enrolled in the study, 4366 (46.61%) and 5002 (53.39%) were male and female, respectively. Among males, 459 (10.51%) had been exposed to the Chinese famine during the fetal stage, whereas 1760 (40.31%) and 1645 (37.68%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Among females, 635 (12.69%) had been exposed to the Chinese famine during the fetal stage, whereas 1988 (39.74%) and 1569 (31.37%) had been exposed to the famine during childhood and adolescence/adult stage, respectively. Regarding the participants with SUA level measurements, 290 (6.64%) reported having Hyperuricemia (HUA) in males and 234 (4.68%) in the females. Furthermore, 1357 (31.08%) reported having hypertension in male and 1619 (32.37%) in the female. In multivariable-adjusted model, famine exposure and serum uric acid were associated with prevalence of hypertension independently in total populations [(1) Model fourd, fatal exposed group vs non-exposed group: 1.25 (95% CI 1.03, 1.52); childhood-exposed group vs non-exposed group:1.60 (95% CI 1.37, 1.87); adolescence/adult exposed group vs non-exposed group: 2.87 (95% CI 2.44, 3.37), P for trend < 0.001; (2) Model four e, high vs normal:1.73 (95% CI 1.44, 2.08)]. When stratified by sex, the results in both males and females were similar to those in the total population. In general, interaction analysis in the multivariable-adjusted model, compared with the combination of normal SUA level and no-exposed famine stage, all groups trended towards higher odds of prevalence of hypertension [the greatest increase in odds, adolescence/adult exposed stage and high SUA level in total participants: OR4.34; 95%CI 3.24, 5.81; P for interaction < 0.001]. When stratified by sex, the results in both males and females were also similar to those in the total population. Conclusion Our data support a strongly positive individual and combined association of famine exposure and serum uric acid with hypertension in middle-aged and elderly Chinese.

Prominent juxtacortical white matter lesion hallmarks NOTCH3-related intracerebral haemorrhage

Background and purposeNOTCH3 p.R544C mutation accounts for 5% of spontaneous intracerebral haemorrhage (ICH) in East Asian patients. We investigated whether certain CT features are associated with NOTCH3-related ICH.MethodsPatients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation. The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation, including burden of white matter lesion (WML), degree of brain atrophy, number of lacunes, prominent juxtacortical WML and prominent lobar lacunes, were analysed by neuroradiologists blinded to the mutation status.ResultsOf 299 patients with spontaneous ICH (mean age, 61 years; male, 68%; ICH volumes, 14.1±17.8 mL), 13 patients (4.3%) carried NOTCH3 p.R544C mutation. The clinical features, haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers. The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML (69.2% vs 17.8%, p<0.001), and the effects were not driven by ageing as seen in patients without mutation. Prominent juxtacortical WML (area under receiver operating characteristic curve=0.76) outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model (OR, 20.9; 95% CI 4.94 to 88.6).ConclusionIn patients with spontaneous ICH, the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.

Abstract 020: C-reactive Protein As A Moderator And Insulin Resistance As A Mediator For The Association Between Endothelin-1 And Type 2 Diabetes Progression Among African Americans In The Jackson Heart Study

Objective: Little is known about the moderation and mediation factors among the association between endothelin-1 (ET-1) level and type 2 diabetes progression in African Americans. We explored the role of high sensitivity C-reactive protein (hsCRP) as a moderator and homeostatic model assessment of insulin resistance (HOMA-IR) as a mediator for the association between ET-1 level and type 2 diabetes progression among African Americans enrolled in the Jackson Heart Study (JHS). Methods: We included 1,692 participants free of prediabetes and diabetes at baseline, who attended Exam 1 of the JHS in 2000-2004 and Exam 3 in 2009-2013, and with measured ET-1 level at Exam 1. Incident prediabetes and diabetes were ascertained at Exam 3. We used a sequential regression model procedure. Zou’s modified Poisson multivariable models were used to calculate risk ratios (RR) and 95% confidence intervals (CI) for prediabetes and diabetes. Effect modification was assessed in the multivariable adjusted model. Valeri and VanderWeele’s mediation analysis approach was utilized to evaluate mediation. Results: A higher log-transformed ET-1 level was detected when comparing non-diabetes versus prediabetes and diabetes participants (p-value for trend = 0.03). Compared to quartile 1 (<0.9 pg/mL) of ET-1, quartile 2 (0.9-1.2 pg/mL) of ET-1 was significantly associated with higher risk of prediabetes (RR=1.19 [95% CI 1.02, 1.38]) and diabetes (RR=1.19 [95% CI 1.02, 1.40]). This association only remained significant for diabetes in the multivariable adjusted model (RR=1.20 [95% CI 1.02, 1.40]) and was not attenuated after adjusted for hsCRP (RR=1.20 [95% CI 1.03, 1.40]), HOMA-IR (RR=1.20 [95% CI 1.02, 1.40]), and both hsCRP and HOMA-IR (RR=1.20 [95% CI 1.03, 1.40]) in quartile 2 of ET-1.The risk of elevated ET-1 level on diabetes was higher in participants with increased hsCRP level in the multivariable adjusted model (RR=1.06 [95% CI 1.02, 1.09]), and further adjusted for HOMA-IR (RR=1.06 [95% CI 1.02, 1.09]. The indirect effect of ET-1 on prediabetes through HOMA-IR is 0.96 (P<0.01), but not found for hsCRP (p=0.26). The total effect of ET-1 on prediabetes mediated by HOMA-IR is 47%. No such mediation effect of HOMA-IR was found among diabetes participants. Conclusions: African Americans with higher ET-1 levels have a higher risk of prediabetes and diabetes. Additionally, the risk of diabetes is elevated among those African Americans with increased hsCRP levels. The mediation analysis result supports that ET-1 is involved in the stage of glucose metabolism imbalances leading to diabetes progression.

Association of the insulinemic potential of diet and lifestyle with risk of diabetes incident in Tehranian adults: a population based cohort study

Background We aimed to assess the associations between insulinemic potential of diet and lifestyle and the risk of diabetes incident, using four empirical indices including the empirical dietary index for hyperinsulinemia (EDIH), the empirical dietary index for insulin resistance (EDIR), empirical lifestyle index for hyperinsulinemia (ELIH), and empirical lifestyle index for insulin resistance (ELIR). Methods A total of 3734 individuals, aged ≥ 20 years old, who were free of diabetes at baseline (2008–2011), were followed for 6.2 years (2015–2018) to ascertain incident diabetes. The food frequency questionnaire was used to collect dietary intakes at baseline. Odds ratio (OR) of diabetes were calculated across quartiles of EDIH, EDIR, ELIH, and ELIR using logistic regression, which controlled for confounding factors. Results The mean ± SD age and BMI of individuals (45.1 % male) were 40.9 ± 12.0 years and 27.1 ± 4.1 kg/m2, respectively. At the end of follow-up, 253 (6.8 %) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest quartile of EDIR (1.58;95 %CI:1.03–2.44, P for trend = 0.025), ELIH (1.89;95 %CI:1.20–2.97, P for trend = 0.004), and ELIR (1.74; 95 %CI:1.11–2.72, P for trend = 0.031) had increased the risk of diabetes. However, no significant associations were found between the score of EDIH and diabetes incident. Conclusions Higher adherence to EDIR, ELIH, and ELIR scores were associated with increased risk of diabetes, while no significant association was found between EDIH score and diabetes incident.

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

ObjectivesTo assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.MethodsWe conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region.ResultsIn study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use.ConclusionsWe found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

Triglyceride–glucose index is associated with the risk of myocardial infarction: an 11-year prospective study in the Kailuan cohort

Background The triglyceride–glucose (TyG) index, which is a simple surrogate marker of insulin resistance, has been suggested as a contributor of cardiovascular disease. However, evidence on the effect of long-term elevation of the TyG index exposure on myocardial infarction (MI) is limited. The current study aimed to evaluate the association of baseline and long-term elevation of the TyG index exposure with the risk of MI. Methods A total of 98,849 participants without MI at baseline (2006) were enrolled from the Kailuan study. The baseline TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was characterized in two ways as follows. The updated mean TyG index was calculated as the mean of TyG index at all previous visits before MI occurred or the end of follow-up; alternatively, the TyG index was calculated as the number of visits with a high TyG index in 2006, 2008, and 2010, ranging from 0 (no exposure) to 3 (had high TyG index at all three study visits). Hazard ratio (HR) and 95% confidence interval (CI) was estimated using multivariable Cox proportion hazard models. Results During a median follow-up of 11.03 years, 1555 incident MI occurred. In the multivariable-adjusted model, the risk of MI increased with quartiles of the baseline and updated mean TyG index, the HR in quartile 4 versus quartile 1 was 2.08 (95% CI,1.77–2.45) and 1.58 (1.18–2.12), respectively. Individuals with a high TyG index at all three visits had a 2.04-fold higher risk (95% CI, 1.63–2.56) of MI compared with no exposure. Subgroup analyses showed that the associations were more pronounced in women than in men (Pinteraction = 0.0411). Conclusions Elevated levels of the baseline and long-term TyG index are associated with an increased risk of MI. This finding indicates that the TyG index might be useful in identifying people at high risk of developing MI.

Massachusetts general hospital Covid-19 registry reveals two distinct populations of hospitalized patients by race and ethnicity

Objective To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). Methods The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N = 866 patients hospitalized with Covid-19 from March 11, 2020—May 4, 2020. Results Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p = 0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001). Conclusions Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

Massachusetts General Hospital Covid-19 Registry reveals two distinct populations of hospitalized patients by race and ethnicity

Objective: To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). Methods: The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N=866 patients hospitalized with Covid-19 from March 11, 2020 - May 4, 2020. Results: Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p=0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001). Conclusions: Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.

Yogurt consumption in relation to mortality from cardiovascular disease, cancer, and all causes: a prospective investigation in 2 cohorts of US women and men

ABSTRACT Background Although a link between regular yogurt consumption and mortality appears plausible, data are sparse and have yielded inconsistent results. Objectives We examined the association between regular yogurt consumption and risk of all-cause and cause-specific mortality among US women and men. Methods A total of 82,348 women in the Nurses’ Health Study and 40,278 men in the Health Professionals Follow-Up Study without a history of cardiovascular disease (CVD) and cancer in 1980 (women) or 1986 (men) were followed up until 2012. Yogurt consumption was assessed by updated validated FFQs. Results During 3,354,957 person-years of follow-up, 20,831 women and 12,397 men died. Compared with no yogurt consumption, the multivariable-adjusted HRs (95% CIs) of mortality were 0.89 (0.86, 0.93), 0.85 (0.81, 0.89), 0.88 (0.84, 0.91), and 0.91 (0.85, 0.98) for ≤1–3 servings/mo, 1 serving/wk, 2–4 servings/wk, and &gt;4 servings/wk in women (P-trend = 0.34), respectively. For men, the corresponding HRs (95% CIs) were 0.99 (0.94, 1.03), 0.98 (0.91, 1.05), 1.04 (0.98, 1.10), and 1.05 (0.95, 1.16), respectively. We further noted inverse associations for cancer mortality (multivariable-adjusted HR comparing extreme categories: 0.87; 95% CI: 0.78, 0.98; P-trend = 0.04) and CVD mortality (HR: 0.92; 95% CI: 0.79, 1.08; P-trend = 0.41) in women, although the latter was attenuated in the multivariable-adjusted model. Replacement of 1 serving/d of yogurt with 1 serving/d of nuts (women and men) or whole grains (women) was associated with a lower risk of all-cause mortality, whereas replacement of yogurt with red meat, processed meat (women and men), and milk or other dairy foods (women) was associated with a greater mortality. Conclusions In our study, regular yogurt consumption was related to lower mortality risk among women. Given that no clear dose–response relation was apparent, this result must be interpreted with caution.