Independent Predictor Of Cardiovascular Disease Events Research Articles

S-48-5: VASCULAR AGEING AND EXERCISE

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Thus, we desperately need tools and approaches that can identify individuals at the asymptomatic, subclinical stage. Numerous studies have demonstrated a progressive decline of arterial function with age, even in the absence of traditional cardiovascular risk factors and overt CVD, which has given rise to the theory that arterial dysfunction (or accelerated vascular ageing) is a primary effect of advancing age and may represent a link between ageing and CVD. Markers of vascular ageing may be such tools, useful for identify those at risk of CVD. Vascular ageing involves the deterioration in vascular structure and function over time, which ultimately leads to end organ damage in the heart, brain and kidney. Markers of vascular ageing are independent predictors of CVD events and mortality. Importantly, it must be recognised that vascular ageing occurs on a continuum across the life course, with its roots in foetal development and thus the importance of promoting healthy vascular ageing starts early in life. Lifestyle interventions such as increasing exercise levels have been shown to have beneficial effects on various markers of vascular ageing. This presentation will summarise the evidence on the association between a physically active lifestyle and vascular ageing and how exercise can be used to delay early vascular ageing it at risk populations.

A comprehensive, contemporary assessment of the association between hepatosteatosis and coronary artery calcium scoring

Abstract Funding Acknowledgements Type of funding sources: None. onbehalf Liverpool Multiparametric Imaging Collaboration Background Coronary artery calcium (CAC) score is a well-established technique for stratifying an individual’s cardiovascular disease (CVD) risk. Several well-established registries have incorporated CAC scoring into CVD risk prediction models to enhance accuracy. Hepatosteatosis (HS) has been shown to be an independent predictor of CVD events and can be measured on non-contrast computed tomography (CT). We sought to undertake a contemporary, comprehensive assessment of the influence of HS on CAC score alongside traditional CVD risk factors. In patients with HS it may be beneficial to offer routine CAC screening to evaluate CVD risk to enhance opportunities for earlier primary prevention strategies. Methods We performed a retrospective, observational analysis at a high-volume cardiac CT centre analysing consecutive CT coronary angiography (CTCA) studies. All patients referred for investigation of chest pain over a 28-month period (June 2014 to November 2016) were included. Patients with established CVD were excluded. The cardiac findings were reported by a cardiologist and retrospectively analysed by two independent radiologists for the presence of HS. Those with CAC of zero and those with CAC greater than zero were compared for demographic and cardiac risks. A multivariate analysis comparing the risk factors was performed to adjust for the presence of established risk factors. A binomial logistic regression model was developed to assess the association between the presence of HS and increasing strata of CAC. Results In total there were 1499 patients referred for CTCA without prior evidence of CVD. The assessment of HS was completed in 1195 (79.7%) and CAC score was performed in 1103 (92.3%). There were 466 with CVD and 637 without CVD. The prevalence of HS was significantly higher in those with CVD versus those without CVD on CTCA (51.3% versus 39.9%, p = 0.007). Male sex (50.7% versus 36.1% p= <0.001), age (59.4 ± 13.7 versus 48.1 ± 13.6, p= <0.001) and diabetes (12.4% versus 6.9%, p = 0.04) were also significantly higher in the CAC group compared to the CAC score of zero. HS was associated with increasing strata of CAC score compared with CAC of zero (CAC score 1-100 OR1.47, p = 0.01, CAC score 101-400 OR:1.68, p = 0.02, CAC score >400 OR 1.42, p = 0.14). This association became non-significant in the highest strata of CAC score. Conclusion We found a significant association between the increasing age, male sex, diabetes and HS with the presence of CAC. HS was also associated with a more severe phenotype of CVD based on the multinomial logistic regression model. Although the association reduced for the highest strata of CAC (CAC score >400) this likely reflects the overall low numbers of patients within this group and is likely a type II error. Based on these findings it may be appropriate to offer routine CVD risk stratification techniques in all those diagnosed with HS.

Platelet-to-lymphocyte ratio is associated with cardiovascular disease in continuous ambulatory peritoneal dialysis patients

BackgroundChronic kidney disease (CKD) patients have a high incidence of cardiovascular disease (CVD) events, which is related to the inflammatory status of this population. Platelet–to–lymphocyte ratio (PLR) is a relatively new indicator of inflammation. The aim of this study was to investigate the relationship between PLR and the CVD events in continuous ambulatory peritoneal dialysis (CAPD) patients. MethodsA total of 70 stable CAPD patients were included in this study from February 2014 to March 2017, and complete demographic characteristics and clinical laboratory baseline data were collected at enrollment. The primary endpoint was defined as the experienced of CVD events during the follow-up period. Binary logistic regression was used to assess the association between PLR and CVD events in CAPD patients. ResultsDuring a median follow-up period of 22 months, 28 (40%) CAPD patients experienced CVD events. Patients in the CVD event group had a high level of platelets (P < 0.01), C-reactive protein (P < 0.01), PLR (P < 0.01) and neutrophil-to-lymphocyte ratio (NLR) (P < 0.01). However, lymphocyte counts (P < 0.01) were significantly lower than patients without CVD events. Following adjusted binary regression analysis revealed no relationship between high NLR and CVD events (OR, 1.21; 95% CI, 0.52–2.85; p = 0.44). However, the correlation between high PLR and CVD events was significant (OR, 1.05; 95% CI, 1.02–1.08; p < 0.01). High PLR was confirmed as an independent predictor of CVD events. ConclusionOur results demonstrated that PLR was independently associated with CVD events. High PLR can be used to predict the risk of CVD events in CAPD patients. PLR was easy to obtain and can be considered as a routine test to serve the clinic.

Observed versus predicted cardiovascular events and all-cause death in HIV infection: a longitudinal cohort study

BackgroundThe aim of the study was to assess the applicability of an algorithm predicting 10-year cardiovascular disease (CVD) generated in the setting of the Framingham Heart Study to a real-life, contemporary Italian cohort of HIV-positive subjects.MethodsThe study was an observational longitudinal cohort study. The probability for 10-year CVD events according to the Framingham algorithm was assessed in 369 consecutive HIV-positive participants free from overt CVD enrolled in 2004, who were followed for a median of 10.0 years (interquartile range, 9.1-10.1). Cardiovascular events included myocardial infarction, hospitalized heart failure, revascularized angina, sudden cardiac death, stroke, peripheral arterial disease.ResultsOver 3097 person-years of observation, we observed a total of 34 CVD events, whereas Framingham algorithm predicted the occurrence of 34.3 CVD events. CVD event rate was 11.0/1000 person-years of follow-up. In a receiver operating characteristics curve analysis, Framingham risk equation showed an excellent predictive value for incident CVD events (c-statistics, 0.83; 95% confidence interval, 0.76-0.90). In a multivariable Cox analysis, age, smoking and diabetes were independent predictors of CVD events. All-cause death rate was 20.0/1000 person-years of follow-up (n = 62 deaths). Causes of death included liver diseases (18), malignancies (14), AIDS-related (11); cardiovascular (9) and others (10). In a Cox analysis, age, AIDS diagnosis and chronic hepatitis were independent predictors of death.ConclusionsObserved CVD events in HIV-infected patients were well predicted by Framingham algorithm. Established major CVD risk factors are the strongest determinants of CVD morbidity in an Italian contemporary cohort of HIV-positive subjects. Interventions to modify traditional risk factors are urgently needed in HIV people.

Skin advanced glycation end products in HIV infection are increased and predictive of development of cardiovascular events.

HIV-1 infection is associated with an increased cardiovascular disease (CVD) risk. Advanced glycation end products are formed as stable markers of glycaemic and oxidative stress. Skin autofluorescence (SAF) as marker of accumulated advanced glycation end products is increased and predictive of CVD events in diabetes mellitus, chronic kidney disease (CKD), and preexisting CVD. We determined SAF levels in HIV-1 infected patients, testing the hypothesis that SAF predicts CVD events in HIV infection. Single-centre prospective cohort study. In 2010-2011, SAF was measured in 91 patients. Development of CVD events was monitored during a median follow-up of 4.8 years. SAF values of the patients were expressed as a ratio (rSAF) to expected SAF levels in age-matched healthy volunteers. Seventy-nine men and 12 women were included, mean age 47 years; 81 patients were on combination antiretroviral therapy. With a mean rSAF of 1.155, SAF levels in patients were 15.5% higher than predicted for their age (95% confidence interval, 10.0-20.0; P < 0.001). In multivariate regression analysis, rSAF was associated with nadir CD4 cell count less than 200 cells/μl (β -0.274; P = 0.01), smoking (β 0.240; P = 0.03), and men who have sex with men (MSM) (β 0.202; P = 0.07). CVD events occurred in six patients (7%). In Cox regression analysis including age, SAF, smoking, diabetes, hypertension and CKD, SAF (P = 0.01), and (Wet Medisch-wetenschappelijk Onderzoek met mensen; WMO) CKD (P = 0.03) remained as independent predictors of CVD events. SAF is increased in HIV-infected patients, and related with smoking, low nadir CD4 cell count, and MSM. Larger studies are needed to confirm whether SAF is an independent predictor of CVD events.

Blood Pressure Response to a Community-Based Program and Long-term Cardiovascular Outcome

The significance in terms of the cardiovascular outcome of different patterns of blood pressure (BP) response to community-based activities has not been previously studied. The aim of our study was to evaluate the relationship between changes of BP observed during a community-based program and long-term rate of cardiovascular disease (CVD) events. A program focused on the prevention of CVDs was implemented in a small city in Argentina over a 6-year period (1997-2003). The program was evaluated using a cohort of 1,526 randomly selected individuals. The population's mean systolic BP (SBP) decreased approximately 5mm Hg, but BP changes were heterogeneous. Eight years after the intervention had stopped, 1,124 individuals of the cohort were surveyed to evaluate incident CVD events. The sample was divided into 3 SBP change categories during the intervention: decrease (< -5mm Hg), no change (-5 to 5mm Hg) and increase (> 5mm Hg). Cox models were used to estimate the hazard ratio (HR) of CVD events for each category adjusted for age, sex, and baseline BP. At the end of the intervention, individuals who had increased their SBP showed an adjusted HR for CVD that was double those whose SBP levels decreased or did not change. An inverse relationship between baseline SBP and ΔSBP was observed: individuals with an increase in BP during the intervention had lower SBP at the beginning of the study. BP increase during the community-based program was an independent predictor of CVD events.

Monocyte Mayhem

Atherosclerosis is a lipoprotein disorder with inflammatory, vascular, and hemodynamic determinants. Total white blood cell count and subpopulations including granulocytes, monocytes, T cells, and bone marrow-derived precursors have been implicated in atherosclerotic cardiovascular disease (CVD).1,2 Although these associations may inform biological processes, they have not, to date, permitted specific mechanistic understanding of subsets of leukocytes involved nor have they advanced risk prediction and therapeutic targeting or monitoring in the clinic. Although short-lived in circulation, blood monocytes are proposed to play a specific role in atherosclerosis because (1) blood monocytes are the major source of tissue macrophages; (2) monocyte-derived macrophages and dendritic cells are the predominant leukocytes in atherosclerotic lesion; and (3) macrophages/dendritic cells have a variety of important proinflammatory (inflammatory recruitment/activation of other leukocytes and vascular cells, foam cell formation and lipid accumulation, fibrous cap erosion, and plaque rupture) and anti-inflammatory (phagocytosis, efferocytosis, and leukocyte egress) actions in experimental atherosclerotic lesions.1,3,4 Despite these mechanistic insights from human pathology and experimental studies in rodents, there have been disparate findings in studies of total monocyte counts and CVD.5,6 Article see p 122 There are several challenges to our understanding of the role of monocytes in atherosclerosis.7,8 First, circulating monocytes are heterogeneous due to subtype differentiation in bone marrow. The regulation and rate of subpopulation recruitment as well as their roles in atherosclerosis are uncertain. Second, monocyte subpopulations are typically defined by differential expression of specific cell surface antigens including receptors that modulate their function, for example, chemokine receptors chemokine (C-C motif) receptor 2 (CCR2), CX3C chemokine receptor 1 (CX3CR1), and C-C chemokine receptor type 5 (CCR5), as well as adhesion molecule integrin receptors very late antigen-4 (also called integrin α4β1) and LFA-1(integrin αLβ …

Coronary artery calcium score improves cardiovascular risk prediction in persons without indication for statin therapy

BackgroundRecent revision to the Canadian Cardiovascular Society (CCS) guidelines on cardiovascular disease (CVD) risk stratification provides expanded recommendations for statin therapy. If CVD risk in the remaining individuals can further be stratified and discriminated by additional risk assessment using coronary artery calcium (CAC) scoring is unknown. Methods and resultsIn a retrospectively analyzed subgroup comprising 1934 participants from the Heinz Nixdorf Recall study, who did not meet criteria for statin therapy based on current CCS guidelines, traditional CVD risk variables and CAC were measured. Between 2000 and 2008, incident CVD events, i.e. coronary deaths, non-fatal myocardial infarction, coronary revascularization, stroke and CV death were determined. Those 43 participants who experienced 55 CVD events (5-year risk to first event: 2.2% (1.6–3.0%)) had higher CAC scores than those who did not (p<0.0001). In multiple Cox regression analysis including age, sex, total-/HDL-cholesterol ratio, and antihypertensive medication, log2(CAC+1) remained an independent predictor of CVD events (HR=1.21 (1.09–1.33), p<0.001). Measures of discrimination improved with the addition of CAC into the model: the incremental discrimination improvement was 0.0167, p=0.014. Net reclassification improvement using risk categories of 0–<3%, 3–10% and >10% was 25.1%, p=0.01, largely driven by a 32.6% correct up-classification in persons with events. Yet, only 38 (2%) of participants were identified being at high risk using CAC imaging in addition to traditional risk factor assessment. ConclusionAdding CAC to traditional risk assessment in persons without indication for statin therapy improves discrimination. However, reclassification to the high risk category and overall event rates seem too low to justify liberal CAC testing in all these individuals.

Low Blood Flow Estimates in Lower-Leg Arteries Predict Cardiovascular Events in Japanese Patients With Type 2 Diabetes With Normal Ankle-Brachial Indexes

To examine the association of baseline measures in lower-leg arteries and conventional cardiovascular risk factors with the incidence of cardiovascular disease (CVD) events in type 2 diabetic patients with normal ankle-brachial indexes (ABIs) (>0.9). We studied 129 type 2 diabetic patients and 35 age-matched nondiabetic subjects with no apparent CVD consecutively admitted to our hospital. At baseline, total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery was evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Patients were followed 4.8 +/- 1.5 years (range 3.0-8.2) or until their first event of CVD. On follow-up, 16 patients developed primary CVD events. Patients with CVD had lower blood flow (P < 0.01) and higher vascular resistance (P < 0.05) than patients without CVD. When the patients were grouped into tertiles according to their levels of total flow volume (129.6-85.5, 85.3-63.3, and 62.7-23.8 ml/min), Kaplan-Meier analysis showed a higher probability of developing CVD events in patients in the lowest than in patients in the highest (P = 0.0199, log-rank test) tertile. Multivariate Cox proportional hazards analysis revealed that the lowest tertile for flow volume (hazard ratio [HR] 8.60, 95% CI 1.61-45.97, P = 0.012), hypertension (3.99, 1.12-14.25, P = 0.033), and smoking status (12.01, 1.21-119.28, P = 0.034) were significant independent predictors of CVD events. We have demonstrated that low blood flow estimates in lower-leg arteries may be predictive for CVD events among Japanese patients with type 2 diabetes even though they have a normal ABI.

Leukocyte Count as a Predictor of Cardiovascular Events and Mortality in Postmenopausal Women

Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women. In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women's Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality. At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein. The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.

Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease.

Resistance to insulin-mediated glucose disposal has been postulated to predispose individuals to a cluster of associated abnormalities (Syndrome X) known to increase risk of cardiovascular disease (CVD). Although several abnormalities subsumed under the rubric of Syndrome X have been shown to predict CVD, there has been no prospective study evaluating the power of insulin resistance, the putative fundamental defect in the syndrome, in this context. Therefore, this study was initiated to evaluate the hypothesis that resistance to insulin-mediated glucose disposal would predict the development of CVD in healthy volunteers. To accomplish this goal, 147 normal, healthy, nonobese, volunteers were evaluated [4.7 +/- 0.1 yr (mean +/- SEM)] after baseline measurements of steady state plasma glucose concentration (an estimate of insulin-mediated glucose disposal), as well as other CVD risk factors. Clinical end points developed in 13 subjects during the follow-up period; hypertension in 5, coronary artery disease in 4, cerebrovascular accident in 3, and peripheral vascular disease in 1. There was a significant univariate relationship between SSPG and CVD (P < 0.002), with the majority of the events taking place in the tertile of subjects with the highest SSPG concentration, i.e. the greatest degree of insulin resistance. In contrast, no CVD events were observed in the tertile with the lowest SSPG concentrations; the most insulin sensitive. SSPG was also related significantly to diastolic blood pressure, triglyceride, and low-density lipoprotein and high-density lipoprotein cholesterol concentrations, and the glucose and insulin responses to oral glucose. All of these relationships were independent of age, gender, body mass index, estimates of physical activity, and smoking history. When SSPG was paired with each of the other variables in a series of multiple regression models, only SSPG, or insulin response, were independent predictors of CVD events. In conclusion, approximately one of every five healthy, nonobese subjects in the most insulin-resistant tertile, followed for approximately 5 yr, had a serious clinical event. These data highlight the importance of insulin resistance as a predictor of CVD.