Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study

AbstractObjectiveWhite blood cells are known to predict cardiovascular mortality, but form a highly heterogeneous population. It is therefore possible that specific subtypes disproportionally contribute to the prediction of cardiovascular outcomes. Therefore, we compared leukocyte subsets alone and in conjunction with an established inflammatory marker, C-reactive protein, for predicting death due to cardiovascular disease in a high-risk population.MethodsPatients, 3316, (mean [SD] age, 62 [10] years) scheduled for coronary angiography were prospectively followed up. Neutrophil, monocyte and lymphocyte counts were determined. Neutrophil and monocyte subsets were further analysed on the basis of surface expression of CD11b, CD18, CD31, CD40 and CD58. Lymphocytes were further subdivided into CD3, CD4, CD8, and CD19 subsets. The association between each marker and subsequent cardiovascular mortality was assessed using multivariable Cox regression models.ResultsDuring a median follow-up period of 7.8 years, 745 (22.5%) patients died, of which 484 were due to cardiovascular events. After entering conventional risk factors and removing patients with a current infection, neutrophil count (HR [95% CI]=1.90 [1.39, 2.60], P<0.001) and the neutrophil/lymphocyte ratio (HR [95% CI]=1.68 [1.24, 2.27], P=0.003) emerged as independent predictors of cardiovascular mortality. After mutual adjustment, neutrophil count (HR [95% CI]=1.87 [1.35, 2.50], P<0.001) out-performed C-reactive protein (HR [95% CI] 1.32 [0.99, 1.78], P=0.06) as a predictor of cardiovascular mortality.ConclusionsDue to its predictive potential and inexpensive determination, assessment of high neutrophil counts may represent an important marker, possibly improving cardiovascular mortality risk prediction

Long-Term Prognostic Impact of CT-Leaman Score in Patients with Non-Obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) Study

BACKGROUND: Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). METHODS: From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. RESULTS: Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. CONCLUSION: CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD.Dr. Min has served on themedical advisory boards Arineta; He is a consultant to Heart Flowand Cardiovascular Research Foundation; and has received research support from GE Healthcare.info:eu-repo/semantics/publishedVersio

Prognostic implications of coronary artery calcium in the absence of coronary artery luminal narrowing

Background and aims: Coronary artery calcium (CAC) scoring is a predictor of future adverse clinical events, and a surrogate measure of overall coronary artery plaque burden. Coronary computed tomographic angiography (CCTA) is a contrast-enhanced method that allows for visualization of plaque as well as whether that plaque causes luminal narrowing. To date, the prognosis of individuals with CAC but without stenosis has not been reported. We explored the prevalence of CAC>0 and its prognostic utility for future mortality for patients without luminal narrowing by CCTA. Methods: From 17 sites in 9 countries, we identified patients without known coronary artery disease, who underwent CAC scoring and CCTA, and were followed for >3 years. CCTA was graded for % stenosis according to a modified American Heart Association 16-segment model. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for incident mortality and compared risk of death for patients as a function of presence or absence of CAC and presence or absence of luminal narrowing by CCTA. Results: Among 6656 patients who underwent CCTA and CAC scoring, 399 patients (6.0%) had no coronary luminal narrowing but CAC>0. During a median follow-up of 5.1 years (IQR: 3.9-5.9 years), 456 deaths occurred. Compared to individuals without luminal narrowing or CAC, individuals without luminal narrowing but CAC>0 were older, more likely to be male and had higher rates of diabetes, hypertension, and dyslipidemia. Individuals without luminal narrowing but CAC experienced a 2-fold increased risk of mortality, with increasing risk of mortality with higher CAC score. Following adjustment, incident death persisted (HR, 1.8; 95% CI, 1.1-2.9, p = 0.02) among patients without luminal narrowing but with CAC>0 compared with patients whose CACS = 0. Individuals without luminal narrowing but CAC ≥100 had mortality risks similar to individuals with non-obstructive CAD (0 < stenosis<50%) by CCTA [HR 2.5 (95% CI 1.3-4.9) and 2.2 (95% CI 1.6-3.0), respectively]. Conclusions: Patients without luminal narrowing but with CAC experienc

Age-dependent and -independent associations between depression, anxiety, DHEAS and cortisol: From the MIPH Industrial Cohort Studies (MICS)

There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608 factory employees ranging between 21 and 62 years. As expected, DHEAS declined with age (r = −0.54, P < 0.001) while there was a modest age-related increase in nocturnal cortisol (r = 0.17, P < 0.001). Depressive symptoms were associated with higher nocturnal cortisol (β = 0.19, P < 0.001), independent of age. While the association between anxiety and cortisol (age by anxiety interaction: β = 0.11, P < 0.05) became stronger with age, there was a similar decline in the DHEAS/cortisol ratio in high-anxious middle-aged adults (β = −0.10, P = 0.018). The current findings suggest that dysphoric mood, and in particular anxiety, may exacerbate the effects of aging on cortisol release. Prospective studies are needed to determine the causal relations between dysphoric mood, cortisol and DHEAS across the lifespan

Influence of heart rate at rest for predicting the metabolic syndrome in older Chinese adults

The aim of this study was to examine the relationship between seated resting heart rate and the metabolic syndrome (MetS) among older residents of Guangzhou, South China. A total of 30,519 older participants (≥50 years) from the Guangzhou Biobank Cohort Study were stratified into quartiles based on seated resting heart rate. The associations between each quartile and the MetS were assessed using multivariable logistic regression. A total of 6,907 (22.8 %) individuals were diagnosed as having the MetS, which was significantly associated with increasing heart rate quartiles (P < 0.001). Participants in the uppermost quartile (mean resting heart rate 91 ± 8 beats/min) of this cardiovascular proxy had an almost twofold increased adjusted risk (odds ratio (95 % CI) = 1.94 (1.79, 2.11), P < 0.001) for the MetS, as compared to those in the lowest quartile (mean resting heart rate, 63 ± 4 beats/min). Heart rate, which is an inexpensive and simple clinical measure, was independently associated with the MetS in older Chinese adults. We hope these observations will spur further studies to examine the usefulness of resting heart rate as a means of risk stratification in such populations, for which targeted interventions should be implemented

Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study

Objective: White blood cells are known to predict cardiovascular mortality, but form a highly heterogeneous population. It is therefore possible that specific subtypes disproportionally contribute to the prediction of cardiovascular outcomes. Therefore, we compared leukocyte subsets alone and in conjunction with an established inflammatory marker, C-reactive protein, for predicting death due to cardiovascular disease in a high-risk population. Methods: Patients, 3316, (mean [SD] age, 62 [10] years) scheduled for coronary angiography were prospectively followed up. Neutrophil, monocyte and lymphocyte counts were determined. Neutrophil and monocyte subsets were further analysed on the basis of surface expression of CD11b, CD18, CD31, CD40 and CD58. Lymphocytes were further subdivided into CD3, CD4, CD8, and CD19 subsets. The association between each marker and subsequent cardiovascular mortality was assessed using multivariable Cox regression models. Results: During a median follow-up period of 7.8 years, 745 (22.5%) patients died, of which 484 were due to cardiovascular events. After entering conventional risk factors and removing patients with a current infection, neutrophil count (HR [95% CI] = 1.90 [1.39, 2.60], P < 0.001) and the neutrophil/lymphocyte ratio (HR [95% CI] = 1.68 [1.24, 2.27], P = 0.003) emerged as independent predictors of cardiovascular mortality. After mutual adjustment, neutrophil count (HR [95% CI] = 1.87 [1.35, 2.50], P < 0.001) out-performed C-reactive protein (HR [95% CI] 1.32 [0.99, 1.78], P = 0.06) as a predictor of cardiovascular mortality. Conclusions: Due to its predictive potential and inexpensive determination, assessment of high neutrophil counts may represent an important marker, possibly improving cardiovascular mortality risk prediction

Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome:the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

OBJECTIVE: Optimal vitamin D levels are associated with reduced cardiovascular and all-cause mortality. We investigated whether optimal 25-hydroxyvitamin D (25[OH]D) is protective in individuals with the metabolic syndrome. RESEARCH DESIGN AND METHODS: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a cohort study of subjects referred for coronary angiography between 1997 and 2000, from which 1,801 with the metabolic syndrome were investigated. Mortality was tracked for a median of 7.7 years. Multivariable survival analysis was used to estimate the association between 25(OH)D levels and mortality. RESULTS: Most subjects (92%) had suboptimal levels of 25(OH)D (<75 nmol/L), with 22.2% being severely deficient (<25 nmol/L). During follow-up, 462 deaths were recorded, 267 (57.8%) of which were cardiovascular in origin. After full adjustment, including the metabolic syndrome components, those with optimal 25(OH)D levels showed a substantial reduction in all-cause (hazard ratio [HR] 0.25 [95% CI 0.13-0.46]) and cardiovascular disease mortality (0.33 [0.16-0.66]) compared with those with severe vitamin D deficiency. For specific cardiovascular disease mortality, there was a strong reduction for sudden death (0.15 [0.04-0.63]) and congestive heart failure (0.24 [0.06-1.04]), but not for myocardial infarction. The reduction in mortality was dose-dependent for each of these causes. CONCLUSIONS: Optimal 25(OH)D levels substantially lowered all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome. These observations call for interventional studies that test whether vitamin D supplementation provides a useful adjunct in reducing mortality in these subjects