IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA1c ...values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (−0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
American College of Cardiology/American Heart Association recently updated their guidelines for hypertension, and lowered the threshold of normal blood pressure (BP). However, the validity of the ...updated guidelines remains controversial. We investigated the relation between the revised BP classification and carotid intima-media thickness, using a community-based cohort. We examined 1,241 subjects who underwent health check-ups at our institute. They were divided into 3 groups based on their BP levels: normal blood pressure (sBP <130 mm Hg and dBP <80 mm Hg, n = 556); stage 1 hypertension (130 mm Hg ≤sBP <140 mm Hg or 80 mm Hg ≤ dBP <90 mm Hg, n = 236); and stage 2 hypertension (sBP ≥140 mm Hg or dBP ≥90 mm Hg, including subjects prescribed with antihypertensive medications, n = 449). With an increase in BP, increase in the mean age, proportion of males, and prevalence of CVD risk factors was seen. The prevalence of carotid plaque, defined as intima-media thickness ≥1.1 mm, also increased with increase in BP. After adjustment with covariates, higher BP was seen to be associated with carotid plaque presence. Atherosclerotic changes are present in stage 1 hypertension even in the healthy population, suggesting the importance of aggressive antihypertensive treatment based on the updated American College of Cardiology/American Heart Association guidelines.
A male preponderance of Parkinson's disease (PD) has been reported in European countries and the USA. To verify this issue in Japanese patients with PD, we examined the age- and gender-specific ...prevalence of PD in Yamagata Prefecture (population 1,244,040), Japan. The prevalence of PD was 61.3/100,000 men and 91.0/100,000 women, showing that women were significantly more affected by PD than men (p < 0.001). Contrary to the findings in Europe and the USA, the results indicate a female preponderance of PD among the Japanese population.
Our aim was to employ novel analytical methods to investigate the therapeutic treatment of the energy regulation dysfunction occurring in a Huntington disease (HD) mouse model. HD is a ...neurodegenerative disorder that is characterized by progressive motor impairment and cognitive alterations. Changes in neuroendocrine function, body weight, energy metabolism, euglycemia, appetite function, and gut function can also occur. It is likely that the locus of these alterations is the hypothalamus. We determined the effects of three different euglycemic agents on HD progression using standard physiological and transcriptomic signature analyses. N171–82Q HD mice were treated with insulin, Exendin-4, and the newly developed GLP-1-Tf to determine whether these agents could improve energy regulation and delay disease progression. Blood glucose, insulin, metabolic hormone levels, and pancreatic morphology were assessed. Hypothalamic gene transcription, motor coordination, and life span were also determined. The N171–82Q mice exhibited significant alterations in hypothalamic gene transcription signatures and energy metabolism that were ameliorated, to varying degrees, by the different euglycemic agents. Exendin-4 or GLP-1-Tf (but not insulin) treatment also improved pancreatic morphology, motor coordination, and increased life span. Using hypothalamic transcription signature analyses, we found that the physiological efficacy variation of the drugs was evident in the degree of reversal of the hypothalamic HD pathological signature. Euglycemic agents targeting hypothalamic and energy regulation dysfunction in HD could potentially alter disease progression and improve quality of life in HD.
Background: Huntington disease (HD) involves neurological and metabolic pathologies.
Results: Euglycemic therapeutics that affect hypothalamic transcription ameliorate multiple aspects of HD pathology.
Conclusion: Hypothalamic targeting in HD may yield enhanced HD drug efficacy.
Significance: Wider consideration of the metabolic aspects of neurological disorders may be important for drug design.
Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of 'neurometabolic' integrity. One of ...the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2
mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2
(GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker,
(cytokeratin 8). Double positive (CD4
CD8
) and single positive CD4
T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic disruption in GIT2KO mice was the unique generation of a novel cervical 'organ',
. 'parathymic lobes'. These novel organs did not exhibit classical peripheral lymph node-like characteristics but expressed high levels of T cell progenitors that were reflexively reduced in GIT2KO thymi. Using signaling pathway analysis of GIT2KO thymus and parathymic lobe transcriptomic data we found that the molecular signaling functions lost in the dysfunctional GIT2KO thymus were selectively reinstated in the novel parathymic lobe - suggestive of a compensatory effect for the premature thymic disruption. Broader inspection of high-dimensionality transcriptomic data from GIT2KO lymph nodes, spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular metabolism and DNA damage. Altered cell clock regulation across both immune and non-immune tissues therefore may be responsible for the premature 'aging' phenotype of GIT2KO mice.
The purpose of this study is to determine whether the angiotensin-converting enzyme (ACE) gene polymorphism is associated with retinal arteriolar narrowing, a subclinical marker of chronic ...hypertension. The Funagata Study examined a population-based sample of Japanese aged 35+ years; 368 participants had both retinal vessel diameter measurements and ACE insertion/deletion (ACE I/D) polymorphism analyses performed. Assessment of retinal vessel diameter and retinal vessel wall signs followed the protocols used in the Blue Mountains Eye Study. ACE gene polymorphisms D/D, I/D and I/I were present in 34 (9.2%), 170 (46.2%) and 164 (44.5%) participants, respectively, distributed in Hardy-Weinberg equilibrium. After multivariable adjustment, retinal arteriolar diameter was significantly narrower in subjects with the D/D genotype compared to subjects with I/D and I/I genotypes (mean difference -6.49 microm, 95% confidence interval (CI): -12.86 microm, -0.11 microm). Our study suggests that the ACE I/D polymorphism may be associated with subclinical structural arteriolar changes related to chronic hypertension.
The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.
We calculated hazard ...ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174374 deaths or major non-fatal vascular outcomes recorded among 1085949 people in 121 prospective studies.
For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.
Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
Abstract
Background
Heart failure (HF) is one of the major complications of infective endocarditis (IE). The ESC guideline described that surgical treatment should be performed for the patients with ...IE complicated with HF. However, decision making of surgical indication in real-world clinical setting is not easy for patients with IE concomitant with HF due to complicated conditions, and the clinical benefit of surgical intervention for IE and HF is unclear.
Purpose
We sought to uncover the association between surgical treatment and in-hospital mortality among the patients admitted for community-acquired IE respectively according to the severity of HF symptoms (NYHA class I to IV).
Methods
We studied 3,403 patients diagnosed as IE (mean age 65.9 years, 61.6% males) with records of baseline NYHA classification (I to IV) who survived for more than 2 days, using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. Patients were classified into four groups: 919 patients (27.0%) in NYHA I, 1,007 patients (29.6%) in NYHA II, 767 patients (22.5%) in NYHA III, and 710 patients (20.9%) in NYHA IV. A multivariable logistic regression model adjusted for age, gender, Barthel Index, Charlson Comorbidity Index, and usage of inotropic therapy at admission was performed to evaluate the association between the surgical treatment and in-hospital mortality.
Results
Patients with higher NYHA classification were significantly older and were more likely to be female than those with lower NYHA classification. At admission, patients with higher NYHA classification had lower baseline activities and higher comorbidities, and also had more complications including stroke, shock and disseminated intravascular coagulation than those with lower NYHA classification. In-hospital mortality was seen in 406 patients (11.9%) in the entire cohort. The mortality rate significantly increased with the NYHA class (NYHA I, 3.6%; NYHA II, 8.4%; NYHA III, 11.9%; NYHA IV, 27.9%: p<0.001). According to the multivariable logistic regression analysis, surgical treatment was independently associated with lower in-hospital mortality (Odds ratio 0.395, 95% Confidence Interval 0.297–0.526; p<0.001). A fragmentated analysis in each NYHA classification showed that the survival benefit of surgical intervention was pronounced in patients with higher NYHA class (Figure). The limitation of our study was including the potential unmeasured confounders, which lead to overestimate the relationship between the surgical treatment and in-hospital mortality even after excluding the critically ill patients who died within 2 days and adjusting for the measured confounders.
Conclusion
Surgical treatment was associated with lower in-hospital mortality among the patients with IE complicated with HF, particularly among those with more advanced HF status. Our study implies that surgical treatment might be beneficial for the patients with advanced HF.
Funding Acknowledgement
Type of funding source: None
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