Previous Cardiovascular Disease Events Research Articles

Abstract 13180: Cardiovascular Disease and Cholesterol Lowering Therapy in Women and Men With Molecularly Proven Familial Hypercholesterolemia

Introduction: Familial Hypercholesterolemia (FH) is an autosomal dominant disease affecting women and men on the same proportion. There is scant evidence on cardiovascular disease (CVD) and therapy adequacy on contemporary FH cohorts according to sex. Goals: Evaluate whether there were differences in CVD outcomes and treatment intensity in women and men with molecularly proven FH at a specialized lipid clinic. Methods: Initially a cross-sectional analysis of 801 patients with FH enrolled between 2011 and 2022 on a genetic cascade screening program was done . All had a positive FH molecular diagnosis. Participants were then followed by a median of 5 years (0.08 to 11 years). Clinical, laboratory and, treatment parameters were compared at baseline and during follow-up according to sex. Results: The cohort consisted of 455 women (57%) and 346 men (43%), mean age 47± 15 years. At baseline there were no sex differences regarding LDL-C (196±74 mg/dL men vs 200±75 mg/dL women, p= 0.567) as well as percentage of those with LDL-C < 100 mg/dL (6.8% men vs 6.1% women, p=0.712) or < 70 mg/dL at baseline (0.3% men vs 0% women, p=0.238). Intensive lipid lowering treatment use was similar between men and women at baseline (75.1% vs. 74.4%; p= 0.848) and during follow-up (87.6% vs. 88.3%; p= 0.785). At baseline 23.1% of women and 38.1% of men had a previous history of CVD (p= 0.000). After follow-up, 41 women (9%) and 52 men (15%) had an incident CVD event (p=0.009). Multivariate Cox regression analysis showed that risk factors related to incident events were age (HR=1.028, 95% CI 1.005-1.052 per year, p =0.019), presence of corneal arcus (HR 1.794, 95% CI 1.096-2.937, p= 0.02), current smoking (HR 2.534, 95% CI 1.304-4.927, p=0.006) and a previous CVD event (HR= 1.793, 95%CI 1.041-3.087, p= 0.035). Conclusions: Overall FH men had a greater risk of CVD events than FH women. There was no difference in treatment intensity and CVD outcomes were associated with traditional risk factors or previous CVD.

Cardiovascular Risk Scores among Asymptomatic Adults with Haemophilia.

The mortality rate of Brazilian people with haemophilia (PwH) is decreasing, but the relative incidence of deaths associated with cardiovascular disease (CVD) is increasing. We aimed to describe the CVD risk score of PwH according to Pooled Cohort Equations Risk (PCER) Calculator tool and its treatment recommendations. We also compared the PCER estimates with the respective Framingham Risk Score (FRS). This cross-sectional study included male PwH ≥ 40 years treated at the Comprehensive Haemophilia Treatment Centre of Pernambuco (Recife/Brazil). PwH with a previous CVD event or a low-density lipid cholesterol ≥ 5.0 mmol/L were excluded. Interviews, medical file reviews, and blood tests were performed. The PCER tool was used to estimate the CVD risk and compare it with the respective FRS. A p-value < 0.05 was accepted as statistically significant. Thirty PwH were included. Median age was 51.5 [interquartile range-IQR; 46.0-59.5] years. The prevalence of obesity, systemic arterial hypertension, diabetes mellitus, hypertriglyceridaemia, hypercholesterolaemia, and hypoHDLaemia were 20%, 67%, 24%, 14%, 47%, and 23%, respectively. The median PCER score was 6.9% [IQR; 3.1-13.2], with 50% having a high risk (PCER ≥ 7.5%). Statin use was suggested for 54% of PwH. Blood pressure was poorly controlled in 47% of PwH. The agreement between PCER and FRS was 80% (κ = 0.60; p = 0.001). Half of the male people with haemophilia aged 40 years or older had a 10-year high risk of developing CVD with strong recommendations to improve control of dyslipidaemia and blood pressure.

Psychological distress and health perception in patients with a previous myocardial infarction or stroke: a national cross-sectional study

BackgroundWhile understanding the impact of mental health on health perception improves patient-centered care, this relationship is not well-established in patients with cardiovascular disease (CVD). We examined the relationship between psychological distress and health perception in patients with a previous myocardial infarction (MI) and/or stroke.MethodsWe extracted data for patients with a previous MI and/or stroke from the 2019 National Health Interview Survey (NHIS). Health perception was self-reported. Presence and severity of anxiety and depression were estimated using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-8 (PHQ-8). Binary analyses of anxiety/depression, multivariable logistic regressions controlling for confounders, and univariable analyses of confounders and anxiety/depression severity were performed.ResultsOf 31,948 individuals for whom data on MI/stroke was available, 1235 reported a previous MI and 1203 a previous stroke. The odds of positive perceived health status were lower for individuals with anxiety/depression compared to those without anxiety/depression in both post-MI (anxiety OR 0.52, 95% CI = 0.32–0.85, P < 0.001; depression OR 0.45, 95% CI = 0.29–0.7, P < 0.001) and post-stroke groups (anxiety OR 0.61, 95% CI = 0.39–0.97, P < 0.001; depression OR 0.37, 95% CI = 0.25–0.55, P < 0.001) upon multivariable analyses. Increasing severity of anxiety/depression was also associated with worse perception of health status upon univariable analysis.ConclusionAmong patients with a previous acute CVD event, those with psychological distress have worse perception of their health status. Understanding the range of patient health perceptions can help physicians provide more patient-centered care and encourage patient behaviors that may improve both CVD and mental health outcomes.

Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case–control study

Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case–control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.

Integration of preprocedural computed tomography scan findings into atherosclerotic cardiovascular disease risk estimation in patients with atrial fibrillation scheduled for catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) and atherosclerosis often coexist due to a shared risk profile. Prior to an AF ablation, computed tomography (CT) scans are routinely performed to assess pulmonary vein anatomy. Often coronary plaques are described as incidental findings. According to current guidelines, patients with coronary plaques on CT are classified as being at very high risk of developing cardiovascular atherosclerotic events, potentially resulting in a redefinition of treatment targets for comorbidities. Purpose This study estimated individual 10-year risks of developing atherosclerotic cardiovascular disease (CVD) events according to the 2021 ESC guideline on CVD prevention before and after the integration of CT-derived coronary plaque information in the risk assessment of AF patients scheduled for catheter ablation. Methods Consecutive AF patients scheduled for catheter ablation were included in the ISOLATION registry (NCT04342312). Patients were excluded from this subanalysis if no preprocedural CT was performed. Each patient was classified as being at low-to-moderate, high, or very high risk of developing CVD in the coming 10 years according to the 2021 ESC guideline on CVD prevention (Figure 1). This classification was based on previous CVD, chronic kidney disease, diabetes mellitus, or the Systematic Coronary Risk Estimation 2 (SCORE2) or SCORE2-Older Persons (SCORE2-OP) risk estimation. The impact of pre-AF ablation CTs on CVD risk was assessed by comparing risk classifications excluding and including information on coronary plaques on CT. Results A total of 1022 patients (age 64 ±9, 664 [65%] male, 686 [67%] paroxysmal AF) was included. Overall CVD risk was high, with 86% of patients at a high (n=190, 19%) or very high (n=693, 68%) 10-year risk of developing CVD events. Coronary plaques were observed in 59% (n=606) of pre-AF ablation CTs. Integration of the CT-derived information on coronary plaques resulted in reclassification of 364 patients (36%) towards the very high risk category (Figure 2). Previous CVD events were observed in 161 very high risk patients (16%). Conclusion In AF patients scheduled for catheter ablation, integration of the information on coronary plaques derived from the pre-AF ablation CT resulted in reclassification of one in three patients towards the very high risk category, which impacted treatment targets for lipid levels and blood pressure.

FRAILTY AND CARDIOVASCULAR DISEASE EVENTS IN COMMUNITY-DWELLING HEALTHY OLDER ADULTS

Abstract BACKGROUND Frailty is associated with adverse outcomes, but whether it independently increases cardiovascular disease (CVD) risk requires clarification. METHODS This study examined the association between frailty in a cohort with no previous CVD events and subsequent CVD outcomes in 19,114 community-dwelling older people from the ASPREE trial. Frailty was assessed using the modified Fried phenotype, comprising weakness, exhaustion, low body mass index (BMI), slowness and low physical activity, and a deficit accumulation frailty index (FI) of 66 items. CVD event was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for heart failure. Results Over a median 4.7-years of follow-up (interquartile range: 3.6 to 5.7 years), pre-frail/frail participants were more likely to develop CVD events (Hazard ratio (HR): 1.33; 95% Confidence Interval (CI): 1.16, 1.53 for pre-frail and HR: 1.68; 95% CI: 1.19, 2.38 for frail participants) according to Fried phenotype. Subtypes of CVD (fatal/non-fatal myocardial infarction and heart failure hospitalization) similarly increased HRs except fatal or non-fatal stroke. These effect sizes were more prominent when frailty was assessed using the FI than that assessed by Fried phenotype. CONCLUSION Pre-frail and frail participants were at significantly increased risk of developing CVD and its sub-types (particularly fatal/non-fatal myocardial infarction and hospitalization for heart failure). Addressing pre-frailty and frailty in older people could contribute to CVD prevention strategies.

Hydroxychloroquine exposure reduces the risk of cardiovasular disease events in patients with hypertension or diabetes mellitus.

To investigate the association of hydroxychloroquine (HCQ) with the risk of cardiovascular disease (CVD) events in patients with traditional risk factors, hypertension (HTN) or diabetes mellitus (DM). We conducted a retrospective cohort study from 1 January, 2010 to 30 September, 2022. There was a total of 1007585 patients from a hospital-based population. In this cohort, 146862 patients had newly diagnosed HTN or DM. Among these patients, 1903 patients had HCQ exposure and 136396 patients had no HCQ exposure after exclusion of previous CVD events or invasive cardiovascular procedures. The risk of developing CVD events, a composite of acute myocardial infarction (AMI) and ischaemic stroke was evaluated. The patients with HCQ exposure had reduced risk of CVD events [HR (hazard ratio)=0.67 95%CI: 0.55-0.83], AMI (HR=0.61, 95%CI: 0.41-0.90) and ischaemic stroke (HR=0.74, 95%CI:0.59-0.93), when compared with non-HCQ exposure, after adjusting for age, sex, rheumatic diseases, comorbidities and medications. Specifically, reduced risk for CVD events (HR=0.67, 95%CI: 0.54-0.83), including AMI (HR=0.67, 95%CI: 0.44-1.00) and ischaemic stroke (HR=0.71, 95%CI: 0.55-0.90) were observed in older patients (age ≥50 yrs) with HCQ exposure, and reduced risk for AMI also observed in younger patients (age <50 yrs) (HR=0.28, 95%CI: 0.08-0.97). Reduced risk for CVD events (HR=0.63, 95%CI: 0.48-0.82) and ischaemic stroke (HR=0.63, 95%CI: 0.47-0.85) were observed particularly in female patients with HCQ exposure. Reduced risk for AMI was observed particularly in male patients with HCQ exposure (HR=0.44, 95%CI: 0.22-0.87). HCQ has protective effect on CVD events, including both AMI and ischaemic stroke in the patients with traditional risk factors. The protective effect of HCQ on CVD events is prominent in older patients.

Hemodialysis Patients with Cardiovascular Disease Reveal Increased Tissue Na+ Deposition

Background: The relationship between Na⁺ balance and cardiovascular disease (CVD) in hemodialysis (HD) patients is not yet fully understood. We hypothesized that HD patients co-diagnosed with CVD show increased tissue Na⁺ accumulation compared to HD patients without CVD. Methods: In our observational study, 52 HD patients were divided into a group with (23 subjects) or without (29 subjects) a positive history of cardiovascular events. We used ²³Na-magnetic resonance imaging (²³Na-MRI) at 3.0 Tesla to quantify Na⁺ content in skin and muscle of both groups directly before and after HD. Additionally, total body fluid distribution was determined by bioimpedance spectroscopy (BIS) and laboratory parameters were assessed. Results: Compared to HD patients without CVD, ²³Na-MRI detected an increased Na⁺ content in skin (21.7 ± 7.3 vs. 30.2 ± 9.8 arbitrary units (a.u.), p < 0.01) and muscle tissue (21.5 ± 3.6 vs. 24.7 ± 6.0 a.u., p < 0.05) in patients with previous CVD events. Simultaneously measured fluid amount by BIS, includingexcess extracellular water (1.8 ± 1.7 vs. 2.2 ± 1.7 L, p = 0.44), was not significantly different between both groups. Tissue Na⁺ accumulation in HD-CVD patients was paralleled by a higher plasma concentration of the inflammation marker interleukin-6 (5.1, IQR 5.8 vs. 8.5, IQR 7.9 pg/mL, p < 0.05). Conclusion: In our cohort, HD patients with CVD showed higher tissue Na⁺ content than HD patients without CVD, while no difference in body water distribution could be detected between both groups. Our findings provide evidence that the history of a cardiovascular event is associated with disturbances in tissue Na⁺ content in HD patients.

Arterial Stiffness Predicts Mortality in Individuals With Type 1 Diabetes.

Type 1 diabetes is accompanied by a significant burden of cardiovascular disease (CVD), which is poorly explained by traditional risk factors. We therefore aimed to explore whether arterial stiffness estimated by the augmentation index (AIx) predicts mortality in individuals with type 1 diabetes. After baseline examination comprising pulse wave analysis by applanation tonometry alongside assessment of traditional cardiovascular risk factors, 906 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study were followed up for a median of 8.2 years (interquartile range 5.7-9.7). Associations between baseline hemodynamics, including AIx, and all-cause mortality as well as a composite of cardiovascular and/or diabetes-related mortality were investigated using multivariable Cox regression models. The 67 individuals who died during follow-up had higher baseline AIx (median 28% [interquartile range 21-33] vs. 19% [9-27]; P < 0.001) compared with those alive. This association was independent of conventional risk factors (age, sex, BMI, HbA1c, estimated glomerular filtration rate [eGFR], and previous CVD event) in Cox regression analysis (standardized hazard ratio 1.71 [95% CI 1.10-2.65]; P = 0.017) and sustained in a subanalysis of individuals with chronic kidney disease. Similarly, higher AIx was associated with the composite secondary end point of cardiovascular and diabetes-related death (N = 53) after adjustments for sex, BMI, eGFR, previous CVD event, and height (standardized hazard ratio 2.30 [1.38-3.83]; P = 0.001). AIx predicts all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in individuals with type 1 diabetes, independent of established cardiovascular risk factors.

HDL (High-Density Lipoprotein) Cholesterol Efflux Capacity Is Associated With Incident Cardiovascular Disease in the General Population.

Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of HDL function metrics with CVD events. The current work aimed to determine, if baseline HDL-C efflux capacity (CEC) is associated with future CVD events in the general population. Approach and Results: We performed a prospective study among participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort (follow-up, 12 years). From the overall n=8592 subjects 325 with previous CVD events were excluded; of the remaining 8267 eligible participants all subjects with new CVD events during follow-up were selected and individually matched to controls for age, sex, smoking status, and HDL-C levels. CEC at baseline was quantified using human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma. Despite identical HDL-C and apoA (apolipoprotein)-I levels between cases (n=351) and controls (n=354) CEC was significantly lower in cases (0.93±0.29 versus 1.01±0.24 arbitrary units; P<0.001). In all subjects combined, CEC correlated positively with HDL-C and apoA-I and negatively with body mass index, hsCRP (high-sensitivity C-reactive protein), and urinary albumin excretion. CEC was inversely associated with incident CVD events, both expressed per quartile and per 1 SD change (odds ratio, 0.73; 95% CI, 0.62-0.86; P<0.001); this association remained significant after adjustments for HDL-C, hsCRP, kidney function, and several other clinical covariates. Combined these data demonstrate that in the general population baseline CEC is significantly associated with the future development of CVD events independent of HDL-C and apoA-I plasma levels.

Soluble ICAM 1 and VCAM 1 Blood Levels Alert on Subclinical Atherosclerosis in Non Smokers with Asymptomatic Metabolic Syndrome

Metabolic syndrome (MetS) is a heterogeneous clinical entity associated with insulin resistance, low-grade proinflammatory balance and impaired endothelial function, accelerating atherosclerosis. Atherosclerotic lesions worsen with age, smoking and co-morbidities, making it difficult to accurately diagnose the cardiovascular disease (CVD) risk. We investigate the association between subclinical atherosclerosis and the presence of blood parameters related to adipocyte and vascular endothelial cell dysfunction, in non-smokers with MetS, under 60 and without previous CVD events. Seventy-eight asymptomatic individuals (average 46.5years, 69% male; 59 MetS and 19 controls) were studied prospectively. Subclinical CVD was defined by the presence of carotid plaque and/or carotid intima-media thickness (CIMT)>0.9 in 2/3D ultrasound-studies, left ventricular hypertrophy (LVH) or high coronary calcium score (CCS). Multiplex immunoassay by Luminex xMAP was performed to measure plasma levels of adipokines and endothelial cell-derived molecules. Compared with controls, MetS patients had higher prevalence of carotid plaque (25 vs. 0%, p=0.01), CIMT>0.9 (73 vs. 26%, p=0.001) and higher CCS (69 vs. 5, p=0.01), which were associated with a remarkable decrease in plasma Omentin levels and increase in sICAM-1, sVCAM-1 and PAI-1 (p<0.05). There was a statistically significant association between CIMT and sICAM-1 (OR: 14.57, 95% CI: 2.56-82.73, p<0.001), sVCAM-1 (OR:7.33, 95% CI: 1,58-33.96, p=0.007) and PAI-1 (OR:7.80, 95% CI: 1.04-22.10, p=0.036) in patients with carotid plaque and/or CIMT>0.9. Positive correlation between plaque volume and sICAM-1 levels was also detected (r=0.40, p=0.045). We demonstrated that the increase of sICAM-1, sVCAM-1 and PAI-1, together with decrease of omentin-1 led to a proinflammatory imbalance pointing to the presence of subclinical atherosclerosis, and improving CVD risk stratification in non-smoking patients at early stage MetS beyond traditional scores.

OP.4A.06] CARDIOVASCULAR RISK IS BETTER REDUCED BY BEDTIME THAN UPON AWAKENING HYPERTENSION TREATMENT-REGIMEN

Objective: In hypertension, ingesting blood pressure (BP)-lowering medications at bedtime, compared to upon awakening, is usually associated with significantly improved reduction of sleep-time BP mean, a sensitive prognostic marker of cardiovascular disease (CVD) risk. The Hygia Project, a research network presently composed of 292 investigators of 40 clinical sites, was specifically designed to test the hypothesis that bedtime chronotherapy entailing the entire daily dose of >1 conventional hypertension medications exerts better ambulatory BP control and CVD risk reduction than all such medications ingested upon awakening. Design and method: We conducted a prospective, randomized, open-label, blinded endpoint trial of 15,674 hypertensive patients (8,682 men/6,992 women, 60.4 ± 13.7 years of age) according to ambulatory BP (ABPM) criteria. Participants were randomized to ingest all their prescribed hypertension medications upon awakening (n = 7,848) or the entire daily dose of at least one of them at bedtime (n = 7,826). Among the later, 3,918 participants were ingesting all medications at bedtime and the remaining 3,908 ingested some medications at bedtime and others upon awakening. At inclusion and at every scheduled clinic visit for ABPM (at least annually) during follow-up, BP was assessed for 48 h. The primary CVD-outcome was the composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke. Results: During a median 5.1-year follow-up, we documented 1,154 major CVD events. Patients of the bedtime, compared with the upon-waking, treatment group showed significantly lower hazard ratio of CVD events, adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, cigarette smoking, HDL-cholesterol, asleep systolic BP (SBP) mean, sleep-time relative SBP decline, and previous CVD event (0.47 [95%CI 0.42–0.54], P < 0.001). CVD risk was further reduced among patients who ingested not just some, but all their BP-lowering medications at bedtime (0.27 [0.21–0.34], P < 0.001, compared with ingestion of all medications upon awakening). Conclusions: In hypertensive patients, ingestion of some (preferably all) BP-lowering medications at bedtime, compared with ingestion of all such medications upon-awakening, results in improved ambulatory BP control (significantly enhanced decrease of asleep BP and increase of sleep-time relative BP decline) and, most importantly, markedly reduced risk of major CVD events.

Excess atherosclerosis in systemic lupus erythematosus,-A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls.

BackgroundSystemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.Methods281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.ResultsMedian age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).ConclusionsIn SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.

Mean platelet volume is associated with lower risk of overall and non-vascular mortality in a general population. Results from the Moli-sani study.

Larger mean platelet volume (MPV) has been associated with adverse health outcomes in high-risk populations or patients with cardiovascular disease (CVD). We tested the association of MPV with mortality in a prospective cohort study including 17,402 subjects randomly recruited from an adult general population within the Moli-sani study (2005-2010). Two distinct subgroups (with or without CVD at baseline) were subsequently analysed. Hazard ratios (HR) were calculated using multivariable Cox-proportional hazard models. Over a median follow up of eight years (137,547 person-years), 925 all-cause deaths occurred (330 vascular, 351 cancer and 244 other deaths). In a multivariable model, the highest MPV quintile (mean MPV=10.0 fL), as compared to the lowest one, was associated with reduced risk of overall mortality (HR=0.79; 95 % confidence interval 0.64-0.98), cancer death (HR=0.70; 0.49-1.00) and death from other non- vascular/non cancer causes (HR=0.55; 0.36-0.84) but not with vascular mortality. The inverse association with overall death appeared even stronger in the subgroup without CVD at baseline (HR=0.64; 0.50-0.81). In contrast, within 920 subjects reporting a previous CVD event, larger MPV was associated with higher risk of total mortality (HR=1.69; 1.05-2.72; p for interaction=0.048) and with a trend of risk for other cause-specific deaths. In conclusion, larger MPV is associated with lower risk of overall and non-vascular death in subjects apparently free from CVD, but appears to be a predictive marker of death in patients with CVD history. The latter is a likely effect modifier of the association between MPV and death.

PP.05.07

Objective: Recent guidelines suggest relying on the ambulatory blood pressure (BP) monitoring (ABPM) derived awake mean to corroborate the diagnosis of hypertension suspected by elevated clinic BP measurement. However, several prospective ABPM studies have found elevated sleep-time BP is a better predictor of cardiovascular disease (CVD) risk than awake BP mean, also in diabetes. We evaluated the combined contribution to CVD risk of clinic, awake, and asleep BP among patients with diabetes participants in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of Northwest Spain. Design and method: This study involved 2632 patients with type 2 diabetes, 1589 men/1043 women, 65.1 ± 11.6 years of age, with baseline BP ranging from normotension to sustained hypertension according to ABPM criteria, prospectively evaluated throughout a 4.1-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed at night and awakening in the morning. Results: The hazard ratios (HR) of total CVD events for each 1-SD elevation in clinic, awake, and asleep systolic BP (SBP) analyzed separately (adjusted for the significant influential characteristics of age, sex, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event) were 1.25 [95%CI: 1.17–1.35]; 1.39 [1.30–1.50], and 1.51 [1.41–1.62], respectively (always P < 0.001). Exploration of the combined contribution of all three BP measurements revealed elevation in asleep SBP (HR = 1.55 [1.38–1.75], P < 0.001) but not in clinic BP (1.08 [0.99–1.18], P = 0.082) or awake BP (0.93 [0.82–1.06], P = 0.270) was the only independent BP parameter significantly associated with increased CVD risk. Conclusions: In patients with diabetes, sleep-time SBP mean, but not daytime clinic BP measurement or ABPM-derived awake BP mean, is the only significant and independent prognostic marker of CVD morbidity and mortality. These findings indicate ABPM, but not conventional clinic BP so far mistakenly used to diagnose hypertension and establish therapeutic targets, is a clinical necessity to accurately detect abnormal sleep-time BP and assess CVD risk in diabetes.

Prolonged P wave duration predicts stroke mortality among type 2 diabetic patients with prevalent non-major macrovascular disease.

BackgroundProlonged P wave duration is a marker of delayed inter-atrial conduction which may predict cardiovascular disease (CVD). Type 2 diabetes is a risk factor for all atherosclerotic manifestations including stroke. We evaluated the prognostic significance of prolonged P wave duration among middle-aged Finnish type 2 diabetes patients with and without prevalent non-major macrovascular disease (PNMMVD) with respect to total and stroke mortality.MethodsWe followed up for 18 years 739 type 2 diabetic patients without previous major CVD event at baseline. Participants were stratified according to P wave duration (<114 or ≥114 ms) and PNMMVD (i.e. coronary heart disease defined as ischaemic ECG changes and typical symptoms of angina pectoris, or claudication; yes or no). The Cox proportional hazards model was used to estimate the joint association between P wave duration, PNMMVD and the mortality risk.ResultsDuring the follow-up, 509 patients died, and 59 of them died from stroke. Those who had prolonged P wave duration had 2.45 (95% confidence interval: 1.11-5.37) increased stroke mortality among PNMMVD patients. In patients without PNMMVD, there was no relationship between P wave duration and stroke mortality.ConclusionsAs an easily measurable factor P wave duration merits further studies with higher number of patients to evaluate its importance in the estimation of stroke risk in type 2 diabetic patients with PNMMVD.

The cardiovascular disease risks of nonthyroidal illness syndrome and inflammatory responses on patients with chronic kidney disease: from the association to clinical prognosis.

Previous data have suggested the potential risk of low serum-free triiodothyronine (FT3) on the cardiovascular disease (CVD) events in patients with end-stage renal disease (ESRD). However, the roles of FT3 and interleukin-6 (IL-6) in the developing of CVD events in patients with chronic kidney disease (CKD) have not been investigated. A total of 176 consecutive patients with CKD underwent thyroid function, IL-6, and echocardiography evaluation. They were divided into two subgroups: group I, 77 patients with IL-6 >200 ng/L, and group II, 99 patients with IL-6 <200 ng/L. The total patients were also divided into two subgroups according to their serum FT3: group A, 83 patients with FT3 <4.0 pmol/L, and group B, 93 patients with FT3 >4.0 pmol/L. Serum FT3 (β = -0.21, P < 0.01), IL-6 (β = 0.48, P < 0.01), and glutathione peroxidase (GSH-Px, β = -0.58, P < 0.01) were found independently associated with left ventricular mass index (LVMI). Patients with higher IL-6 had significantly higher CVD incidence than those with IL-6 <200 ng/L (HR 1.98, P = 0.014); Patients with lower FT3 had significantly higher CVD incidence than those with FT3 >4.0 pmol/L (HR 1.81, P = 0.038), when extensive demographics, comorbidities and laboratory adjustments were made. Serum levels of FT3 and IL-6 were associated with the LVMI and previous CVD events; lower FT3 and higher IL-6 were strong predictors of subsequent CVD events in patients with CKD.

CD4/CD8 ratio is not predictive of multi-morbidity prevalence in HIV-infected patients but identify patients with higher CVD risk.

BackgroundCD4/CD8<0.8 is a surrogate marker of immune-activation/immunosenescence and independently predicts mortality in the HIV-infected patients due to non-AIDS related events. Most studies showed that patients on antiretroviral therapy (ART) often fail to normalize the CD4/CD8 ratio despite CD4 count normalization. Primary objective of the study was to explore the impact of CD4/CD8<0.8 as independent predictor of HIV-associated non-AIDS (HANA) conditions and multimorbidity (MM) in HIV patients. In patients with no previous history of cardiovascular disease (CVD) a particular insight is provided in the association between impact of CD4/CD8<0.8 and risk prediction of CVD or radiological markers of subclinical CVD.Materials and Methods914 consecutive patients attending Modena Metabolic HIV Clinic were evaluated in a cross-sectional retrospective study. Inclusion criteria: stable ART from ≥2 years; HIV-RNA plasma levels<40 copies/mL; stable CD4 count≥350/mmc. CD4/CD8 strata (0.8) was chosen as a cut off representing the median value of the cohort. MM was defined as the presence of≥2 HANA conditions including standard defined: chronic kidney disease, hypertension, previous CVD events, osteoporosis and diabetes mellitus. Calendar year of ART initiation was defined: “PreART” (<2000); “EarlyART” (2000–2005) and “LateART” (>=2006). High CVD risk was defined for Framingham Risk Score (FRS)≥6. Subclinical CVD was defined using cardiac CT scan for calcium score (CAC)≥100. Logistic univariate and multivariable adjusted analysis were performed to assess relationships between variables.ResultsDemographic and HIV-specific variables distribution in patients with and without MM are shown in Table 1. Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD8>0.8.In multivariable analyses CD4/CD8<0.8 was not an independent predictor of MM (OR=1.225, CI 0.891; 1.681, p=0.211) after adjustment for age, gender and BMI. Patients with CD4/CD8<0.8 displayed higher CVD risk but not higher prevalence of subclinical CVD. At multivariable analyses CD4/CD8<0.8 remained predictor of higher CVD risk (OR=0.65, CI 0.47–0.917, p=0.014) after correction for sex, BMI, age strata and HIV infection duration.ConclusionsLow CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent prepredictor of enhanced CVD risk. This may support role of immune-activation/senescence in the pathogenesis of CVD.

Patient Empowerment Programme in primary care reduced all-cause mortality and cardiovascular diseases in patients with type 2 diabetes mellitus: a population-based propensity-matched cohort study.

To assess whether a structured diabetes education programme, the Patient Empowerment Programme (PEP), was associated with a lower risk of first cardiovascular disease (CVD) event and all-cause mortality in a population-based cohort of patients with type 2 diabetes mellitus (T2DM) in primary care. A Chinese cohort of 27 278 patients with T2DM and without previous CVD events on or before the baseline study recruitment date was linked to the Hong Kong administrative database from 2008 to 2013. The PEP was provided to patients with T2DM treated at primary care outpatient clinics through community trained professional educators. PEP non-participants were matched one-to-one with the PEP participants using a propensity score method with respect to their baseline covariates. Cox proportional hazard regression was performed to estimate the associations of the PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics. During a median of 21.5 months follow-up, 795 (352 PEP participants and 443 PEP non-participants) patients experienced a first CVD event. After adjusting for confounding variables, PEP participants had a lower rate of all-cause mortality [hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.445-0.715; p < 0.001], first CVD (HR 0.807, 95% CI 0.696-0.935; p = 0.004) and stroke (HR 0.702; 95% CI 0.569-0.867; p = 0.001) than those without PEP. Enrolment in the PEP was associated with lower all-cause mortality and a lower number of first CVD events among patients with T2DM. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and the enhancement of quality of diabetes care in primary care.

Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes

AimDiabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire±FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.MethodsParticipants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).Results218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).ConclusionSAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM’s value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.