Early Cardiovascular Disease Risk Research Articles

Cardiovascular Comorbidity Associated With Albuminuria in Youth-Onset Type 2 Diabetes: Analyses From the iCARE Study

ObjectivesLittle is known about the relationship between albuminuria in youth with type 2 diabetes (T2D) and cardiovascular risk. We aimed to determine whether youth with T2D and albuminuria have evidence of increased cardiovascular risk and/or early cardiovascular dysfunction compared with youth with T2D without albuminuria. MethodsYouth with T2D were stratified by albuminuria status. Cardiovascular risk factors, including body mass index (BMI), 24-hour blood pressure, lipid profile, smoking and smoking exposure, habitual physical activity and screen time, were compared between groups. Left ventricular structure and function and carotid intima-media thickness (cIMT) were evaluated in participants who underwent cardiac imaging. ResultsTwo hundred sixty-five youth participated, 83 (31.3%) of whom had albuminuria. Ethnicity, sex, BMI z score, age at diagnosis, duration of diabetes and hepatocyte nuclear factor-1alpha status did not differ between youth stratified by albuminuria. Smoking, exposure to second-hand smoke and low physical activity levels did not differ between groups. Youth with albuminuria were more likely to have hypertension, dyslipidemia and poor glycemic control. Left ventricular structure and carotid cIMT did not differ between groups, but youth with albuminuria had evidence of early left ventricular diastolic dysfunction. ConclusionsWe found evidence of increased cardiovascular disease risk factors and left ventricular diastolic dysfunction in youth with T2D and albuminuria compared with those without albuminuria, despite a relatively short duration of disease. Thus, albuminuria may serve as a marker of early cardiovascular disease risk in youth with T2D.

Abstract 14819: Excess Epicardial Fat Volume is Associated With Increased Cardiovascular Structural and Functional Abnormalities in Menopausal Women Regardless of Body Weight: The Higher the Epicardial Fat Volume, the Higher the Abnormalities

Background: It has been reported that an increase in epicardial fat volume (EFV) has been associated with an increase in cardiovascular structural and functional abnormalities (CVSFA). Purpose: The purpose of this study is to assess whether a step-wise increase in EFV is associated with a proportional increase in CVSFA. Methods: We screened 2,756 asymptomatic subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System (ECVDRS), which consists of 10 tests; 7 are vascular and 3 are cardiac. The vascular tests are: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post-mild protocol exercise (PME), CIMT, abdominal aorta ultrasound, retinal photography, and microalbuminuria. The 3 cardiac tests are: Pro-BNP, ECG, and LV ultrasound. Additional tests are waist circumference, BMI, fasting blood sugar, lipid profile, and CRP. 596 out of the total subjects were asymptomatic, and out of these 220 (37%) underwent cardiac CT for coronary artery calcium scoring (CACS) and EFV determination using Siemens Somatom Definition Dual source CT scanner 64x2. 107 out of the 220 were females (48%). These females were divided into 5 groups based on their EFV: 24 with < 69cm 3 ; 33 between 70cm 3 and 94cm 3 ; 16 between 95cm 3 and 119cm 3 ; 20 between 120cm 3 and 144cm 3 ; and 14 >145cm 3 . Results: As noted in the table, a step-wise increase in EFV was associated with proportional increases in CVSFA, specifically CACS, resting BP, abnormal rise in BP-PME, CRP, and triglycerides. An increase in EFV was noticeably associated with an increase in resting blood BP by a 10mmHg difference between the group whose EFV < 120cm 3 and those whose EFV is > 120cm 3 . Conclusions: Based on our data, we feel that excess EFV appears to be the villain for most CVSFA. Accordingly, we urge all healthcare professionals that it is time to focus on early and accurate assessment of this significant risk marker, which is the culprit for many CVD risk factors. Early detect to protect.

The gender-specific role of prediabetes on 10-year cardiovascular disease incidence: highlights from the ATTICA prospective (2002–2012) study

Abstract Background/Introduction Prediabetes in terms of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) are highly discussed for their aggravating effect on cardiac health and their potential inclusion in risk prediction to achieve earlier prevention. Purpose The aim of the present work was to evaluate the association between prediabetes and 10-year first fatal/non fatal cardiovascular disease (CVD) incidence in a sample without prevalent CVD, taking into account the stability of this condition or the transition to type II diabetes. Methods A prospective study was conducted during 2001–2012 studying n=1,514 males and n=1,528 females (aged >18 years old) free of CVD. According to American Diabetes Association Diagnosis, prediabetes in terms of IFG was defined as fasting glucose levels 100–125 mg/dl while type 2 diabetes as fasting blood glucose >125 mg/dl or the use of antidiabetic medication. Ten-year follow-up was performed in n=2,020 participants (n=317 CVD cases); the working sample here was n=1,485 (n=249 CVD cases) (without baseline diabetes and with available data on diabetes status at follow-up). Results Of the 1,485 participants, n=279 had IFG, at baseline. Ten-year CVD incidence was 19.3% in IFG subgroup and 12.3% in normoglycemic subgroup (p<0.001); the IFG-to-normoglycemic CVD incidence ratio in men was 1.22 while in women 1.60. Multi-adjusted analysis revealed that IFG was an independent predictor of CVD within the decade (Hazard ratio (HR)=1.39, 95% Confidence Interval (95% CI) (1.00, 1.95)). Significant interacting effect of gender on the examined association was revealed (p for interaction=0.001); in stratified analysis, IFG was independently associated with increased CVD risk only in women (HR=1.47, 95% CI (1.10, 2.68)). Within the decade, transition to diabetes status was observed in about one out of four participants with prediabetes (25.1%) while the respective rate in normoglycemic participants was 10% (n=191 diabetes cases, in total). Interestingly, sensitivity analysis revealed that when this category (with diabetes onset within the decade) was excluded from the analysis prediabetes retained its independent aggravating –even weaker– effect on 10-year CVD risk in total sample (HR=1.18, 95% CI (1.01, 1.91)) as well as in women (HR=1.25, 95% CI (1.03, 2.97)). Conclusion Here, it was suggested that IFG independently predicted long-term CVD onset, even without transition to a more serious cardiometabolic condition (i.e. diabetes) with more evident outcomes in case of women. Considering the increasing interest for early CVD risk prediction, prediabetes condition in terms of IFG may be a useful predictor towards this perspective. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003].

Cardiovascular disease risk assessment in patients with familial Mediterranean fever related renal amyloidosis

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and 126 patients with GN group. Forty-seven CVDEs were observed during the 4.2-years follow up; all 28 patients in the FMF-amyloidosis group and 14/19 patients with GN developed CVDEs before the age of 40 (p = 0.002). CVD mortality was 2.8 times higher (95% CI 1.02–7.76) in patients with FMF-amyloidosis. Across both groups, FMD and FGF23 (p < 0.001) levels were independently associated with the risk of CVDEs. Patients with FMF-amyloidosis are at increased risk of early CVDEs with premature mortality age. FGF 23, FMD and hsCRP can stratify the risk of early CVD in patients with FMF-related AA amyloidosis.

Adipokines in young survivors of childhood acute lymphocytic leukemia revisited: beyond fat mass.

PurposeThis cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors.MethodsA multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines.ResultsThis study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18–24 Gy). The BMI z-score, the FMI, and sex (P<0.050 for all) influenced at least one adipokine, while cranial radiotherapy exposure was marginal in model 2. Parameter estimates from the MANCOVA's final model showed that the BMI z-score (β=-0.437, P=0.010) and the FMI (β=-0.209, P=0.004) negatively influenced adiponectin, while the FMI positively affected resistin (β=0.142, P=0.020). The relationship between leptin, visfatin, and the adiposity ndexes could not be established. In model 1, females presented with increased adiponectin (β=-1.014, P=0.011) and resistin (β=-1.067, P=0.002) levels; in model 2, female sex positively affected adiponectin (β=-1.515, P=0.001) and marginally influenced resistin (β=-0.707, P=0.054) levels. Cranial radiotherapy negatively determined visfatin levels in both final models (P<0.050).ConclusionsChanges in body fat may be associated with adipose tissue dysfunction and should be carefully evaluated in survivors of acute lymphocytic leukemia, considering both sex and cranial radiotherapy exposure, to treat disorders that may possibly aggravate their risk for early cardiovascular disease.

Atherogenic Lipid Ratios Related to Myeloperoxidase and C-Reactive Protein Levels in Psychotic Disorders.

BackgroundCardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders.MethodsAs a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors.ResultsA markedly higher proportion (26%–31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses.ConclusionsOur findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies.

Obesity, overweight and risk for cardiovascular disease and mortality in young women.

The aim of this study was to investigate the relation between body mass index (BMI) in young women, using weight early in pregnancy as a proxy for pre-pregnancy weight, and risk for early cardiovascular disease (CVD) and mortality. In this prospective, registry-based study, we used weight data in early pregnancy from women, registered in the Swedish Medical Birth Registry, and who gave birth between 1982 and 2014 (n = 1,495,499; median age 28.3 years). Of the women, 118,212 (7.9%) were obese (BMI ≥ 30 kg/m2) and 29,630 (2.0%) severely obese (BMI ≥ 35 kg/m2). After a follow-up of median 16.3 years, we identified 3295 and 4375 cases of acute myocardial infarction (AMI) and ischemic stroke (IS) corresponding to 13.4 and 17.8 per 100,000 observation years, respectively, occurring at mean ages of 49.8 and 47.3 years. Compared to women with a BMI 20-<22.5 kg/m2, the hazard ratio (HR) of AMI increased with higher BMI from 1.40 (95% confidence interval (CI) 1.27-1.54) among women with BMI 22.5-<25.0 kg/m2 to 4.71 (95% CI 3.88-5.72) among women with severe obesity, with similar findings for IS and CVD death, after adjustment for age, pregnancy year, parity and comorbidities at baseline. Women with BMI 30-<35.0 and ≥35 kg/m2 had increased all-cause mortality with adjusted HR 1.53 (95% CI 1.43-1.63) and 1.83 (95% CI 1.63-2.05), respectively. A significant increase in the risk for early AMI, IS and CVD death was noticeable in overweight young women, with a marked increase in obese women.

Impact of preventive screening and lifestyle interventions in women with a history of preeclampsia: A micro-simulation study.

Preeclampsia is a female-specific risk factor for the development of future cardiovascular disease. Whether early preventive cardiovascular disease risk screenings combined with risk-based lifestyle interventions in women with previous preeclampsia are beneficial and cost-effective is unknown. A micro-simulation model was developed to assess the life-long impact of preventive cardiovascular screening strategies initiated after women experienced preeclampsia during pregnancy. Screening was started at the age of 30 or 40 years and repeated every five years. Data (initial and follow-up) from women with a history of preeclampsia was used to calculate 10-year cardiovascular disease risk estimates according to Framingham Risk Score. An absolute risk threshold of 2% was evaluated for treatment selection, i.e. lifestyle interventions (e.g. increasing physical activity). Screening benefits were assessed in terms of costs and quality-adjusted-life-years, and incremental cost-effectiveness ratios compared with no screening. Expected health outcomes for no screening are 27.35 quality-adjusted-life-years and increase to 27.43 quality-adjusted-life-years (screening at 30 years with 2% threshold). The expected costs for no screening are €9426 and around €13,881 for screening at 30 years (for a 2% threshold). Preventive screening at 40 years with a 2% threshold has the most favourable incremental cost-effectiveness ratio, i.e. €34,996/quality-adjusted-life-year, compared with other screening scenarios and no screening. Early cardiovascular disease risk screening followed by risk-based lifestyle interventions may lead to small long-term health benefits in women with a history of preeclampsia. However, the cost-effectiveness of a lifelong cardiovascular prevention programme starting early after preeclampsia with risk-based lifestyle advice alone is relatively unfavourable. A combination of risk-based lifestyle advice plus medical therapy may be more beneficial.

Risk of hospitalization for early onset of cardiovascular disease among infertile women: a register-based cohort study.

Is female infertility predictive of a woman's future risk of early cardiovascular disease (CVD)? Female infertility does not seem to be predictive of early CVD during a mean follow-up of 9 years. Associations between infertility and comorbidity have been found in several studies, but data on the association between female infertility and risk of CVD are scarce and inconclusive. In this nationwide cohort study, we included 87 221 women registered in the Danish National IVF register, undergoing medically assisted reproduction (MAR) between 1st of January 1994 and 31st of December 2015. The cohort was followed for incident hospitalization due to CVD in the Danish National Patient Register from enrollment to 31 December 2015. Women with a history of CVD prior to enrollment were excluded. Cox proportional hazard models with age as the underlying time scale were used to estimate hazard ratios (HR) with 95% CI of CVD among women with an infertility diagnosis, compared to women without an infertility diagnosis. All analyses were adjusted for educational attainment. Female infertility and the reason for infertility was diagnosed and registered in the IVF register by specialists in Danish public and private fertility clinics since 1st of January 1994. In our cohort, 53 806 women (61.7%) were diagnosed with female factor infertility, while 33 415 (38.3%) did not have a female factor infertility diagnosis and made up the reference group. A total of 686 (1.3%) infertile women were hospitalized for CVD compared to 250 (0.7%) among women without an infertility diagnosis during a mean follow-up time of 9 years. We found no increased risk of early CVD in our analyses (adjusted HR 0.98, 95% CI: 0.85;1.14). Likewise, analyses stratified by specific infertility diagnosis, showed no risk difference. We were unable to adjust for confounding parameters such as body mass index, cigarette smoking or alcohol consumption. These results may not be generalizable to infertile women who do not seek out fertility treatment, or infertile women with other lifestyle characteristics than Danish women. Diagnosing female infertility or the time of MAR does not seem to be a window of opportunity where early screening for cardiovascular disease risk factors can have a prophylactic potential. This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. None of the authors declare any conflict of interest.

Abstract 135: Impaired Autonomic Function in Young Adults Born Preterm With Very Low Birth Weight is Associated With Elevated Serum Uric Acid Levels

Preterm birth increases the risk of cardiometabolic disease. We showed that prematurity induces programming effects that lead to elevated blood pressure (BP), higher serum uric acid, and impaired autonomic control characterized by reduced heart rate variability (HRV), baroreflex sensitivity (BRS), and elevated ratio of low frequency to high frequency power (LF/HF), a marker of sympathovagal balance. However, the relationships among these factors in subjects born preterm are undefined. Since uric acid has been shown to correlate with HRV in adult hypertensive subjects, we hypothesized that higher uric acid is associated with impaired autonomic function in subjects born preterm. Methods: A cohort of 131 young adults born preterm was compared to a cohort of 26 born term (19.6 years). Serum uric acid was measured. BP and ECG were recorded continuously for analysis of autonomic function reflected in HRV and BRS. We used generalized linear models to estimate the association between uric acid and measures of HRV and BRS, adjusting for race, age at follow up, and BMI. The potential interaction between uric acid and preterm birth was tested by introducing an interaction term and, if suggestive of an interaction (p ≤ 0.1), estimates were calculated within strata (preterm &amp; term). Results: Compared to term, preterm participants had higher serum uric acid levels (5.2 mg/dL, IQR: 4.2, 6.2 vs 4.8 mg/dL, IQR: 3.9, 6.0) and lower HRV as measured by standard deviation of normal to normal RR intervals (71 ms, IQR: 54, 97 vs 80 ms, IQR: 55, 101). Across term and preterm groups combined, uric acid was inversely associated with BRS measured as HF alpha ( β : -0.12, 95% CI -0.20 to -0.03, p for interaction = 0.06). Assessment of interaction showed this association was significant in preterms only ( β : -0.15, 95% CI -0.24 to -0.06 vs 0.07, -0.17 to 0.30). Uric acid was positively associated with LF/HF ( β : 0.13, 95% CI 0.01 to 0.25, p for interaction=0.01). Conclusions: Young adults born preterm had dampened parasympathetic control of heart rate and BP, and higher serum uric acid was associated with sympathovagal imbalance. The data suggest that alterations of uric acid metabolism associated with preterm birth may increase the risk of early cardiovascular disease in part by impairing autonomic control

Carbohydrate metabolism in patients with familial hypercholesterolemia: Data from the HELLAS-FH registry

Aim: Patients with familial hypercholesterolemia (FH) have increased risk of early cardiovascular disease and require intensive hypolipidemic treatment with statins and ezetimibe. Statin therapy is associated with an increased risk of type 2 diabetes mellitus (T2DM). The aim of this analysis was the evaluation of glycemic profile, as well as of the risk of T2DM in subjects with FH in Greece.

Elevated Fasting Plasma ApoB-lipoprotein Remnants are Associated with MetS and PCOS: Early Cardiovascular Disease Risk in Adolescents

Elevated Fasting Plasma ApoB-lipoprotein Remnants are Associated with MetS and PCOS: Early Cardiovascular Disease Risk in Adolescents

Preterm Adolescents Exhibit Higher Blood Pressure and Sodium Retention with Higher Uric Acid and Differential Circulating Renin‐Angiotensin System Expression

Preterm birth increases the risk of developing early cardiovascular disease in the future, but the underlying mechanisms are poorly understood. We previously showed that adolescents born preterm have higher blood pressure (BP), blunted pressure natriuresis, higher angiotensin II (Ang II) but lower Ang‐(1–7), and higher uric acid. The influence of preterm birth on uric acid metabolism may foster an increased risk of cardiovascular disease in part through chronic alterations in the renin‐angiotensin system (RAS) and increased sodium retention. Thus, we hypothesize that the preterm birth‐induced increase in uric acid correlates with higher BP, attenuated sodium excretion, and differential RAS expression with higher Ang II and lower Ang‐(1–7) in adolescence.A cohort of 175 adolescents born preterm was compared to 51 term controls. We recorded systolic and diastolic BP z‐scores. Circulating levels of Ang II and Ang‐(1–7) were quantified, their ratio calculated, and evaluated in relation to serum uric acid, spot urine sodium‐to‐creatinine ratios, and BP using Spearman correlation coefficients and generalized linear models by preterm birth status.Compared to those born term, adolescents born preterm had higher mean systolic and diastolic BP z‐scores (−0.4 vs −0.86, p&lt;0.001, and −0.26 vs −0.53, p=0.03, respectively) and a higher rate of hypertension (12% vs 2%, p=0.03). Higher SBP z‐score correlated with a higher Ang II:Ang‐(1–7) ratio (coefficient 0.18, p=0.02) and higher uric acid (β: 0.11 mg/dL, 95% CI 0.002 to 0.22 mg/dL). Higher serum uric acid correlated with lower Ang‐(1–7) (β: −0.02 pmol/L, 95% CI −0.04 to −0.001 pmol/L) and a higher Ang II:Ang‐(1–7) ratio (β: 0.04, 95% CI 0.008 to 0.08). Plasma Ang II correlated with a lower urine sodium:creatinine ratio (β: −0.01 pmol/L, 95% CI −0.02 to −0.004 pmol/L), a relationship that was stronger in adolescents born preterm compared to term (β: −0.01 pmol/L, 95% CI −0.02 to −0.001 pmol/L vs β: 0.001 pmol/L, 95% CI −0.009 to 0.01 pmol/L, interaction term p=0.04).In summary, the present study finds that in adolescents born preterm who have higher uric acid, BP, plasma Ang II, and lower Ang‐(1–7), higher plasma Ang II relative to Ang‐(1–7) correlated with higher serum uric acid, lower urinary sodium excretion, and higher BP. We propose that prematurity may increase the risk of early cardiovascular disease in part through increased circulating levels of uric acid that may differentially influence the expression of Ang II and Ang‐(1–7), leading to increased sodium retention and elevated BP.Support or Funding InformationEunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD047584; HD084227), the American Heart Association (AHA 14GRNT20480131), the Clinical Research Unit of Wake Forest Baptist Medical Center (MCRR/NIH M01‐RR07122), the Wake Forest Clinical and Translational Science Award (NIH UL1 TR001420), and Forsyth Medical Center and Wake Forest School of Medicine Department of Pediatrics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Angiotensin Receptor Expression and Vascular Endothelial Dysfunction in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with vascular endothelial dysfunction (VED) in otherwise healthy patients. The role of renin-angiotensin system (RAS) in the OSA induced VED is not well understood. Recently diagnosed OSA patients with very low cardiovascular disease (CVD) risk (Framingham score <5%) were studied at diagnosis and after 12 weeks of verified continuous positive airway pressure (CPAP) therapy. Participants underwent biopsy of gluteal subcutaneous tissue at baseline and after CPAP. Microcirculatory endothelial expression of angiotensin receptors type-1 (AT-1) and type-2 (AT-2) was measured in the subcutaneous tissue using quantitative confocal microscopy techniques. The ex-vivo effect of AT-1 receptor blockade (ARB) on endothelial superoxide production was also measured before and after CPAP treatment. In OSA patients (n = 11), microcirculatory endothelial AT1 expression decreased from 873 (200) (fluorescence units) at baseline to 393 (59) units after 12 weeks of CPAP (P = 0.02). AT2 expression did not decrease significantly in these patients (479 (75) to 329 (58) post CPAP (P = 0.08)). The ex-vivo addition of the losartan to the microcirculatory endothelium resulted in decreased superoxide expression in the vascular walls from 14.2 (2.2) units to 4.2 (0.8) P < 0.001; while it had no effect on post-CPAP patient tissue (P = 0.64). In OSA patients with no to minimal CVD risk, VED is associated with upregulation of AT-1 expression that is reversible with CPAP. Endothelial oxidative stress was reversible with ARB. RAS activation may play an important role in the development of early CVD risk in OSA patients.

A VACCINE-BASED STRATEGY FOR REDUCING CARDIOVASCULAR DISEASE RISK FACTORS

Introduction: Elevated levels of serum LDL-cholesterol (LDL-C) and triglycerides have independently been found to confer increased risk of early cardiovascular disease (CVD). Naturally occurring loss-of-function mutations in two host proteins that are involved in lipid metabolism, Proprotein

Abstract 13128: Novel Markers and Tools for Early Assessment of CV Risk Beyond Framingham and ACC/AHA Guidelines

Introduction: Framingham risk score (FRS) has been widely used, despite its sub-optimal contribution for early CVD risk stratification, mainly in women. The ACC/AHA atherosclerotic cardiovascular disease (ASCVD) score has been recently introduced as an improvement to FRS for CV risk assessment. Hypothesis: The aim of this work was to assess if blood pressure rise post mild exercise (BPrisePME) and abnormal pro-BNP is an appropriate tool for early detection of structural and functional CV abnormalities in asymptomatic subjects. Methods: We screened 2406 asymptomatic subjects, age 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System (ECVDRS), which consists of 10 tests: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post mild exercise (PME), Carotid Intima Media Thickness (CIMT), abdominal aorta and left ventricle ultrasound (LVUS), retinal photography, microalbuminuria, ECG, and pro-BNP. Abnormal blood pressure rise post mild exercise (BPrisePME) was defined as systolic BP rise &gt;30mmHg post 3-min-walk at 7% elevation, 2.5mph. Normotension (NT), pre-hypertension (pre-HTN), and hypertension (HTN) were defined according to JCN7 criteria. Results: Among the 2406 subjects, 1482 were in the age range 40-79, not taking any CV medication. These subjects, 841 female and 641 male, were stratified according to ASCVD, FRS and ECVDRS risk scores, respectively and assigned to low (L), intermediate (I) or high (H) risk. Prevalence of abnormal structural and functional abnormalities is in Table. Conclusions: Based on our data, 1. Abnormal rise in blood pressure prevalence correlates with the risks (L, I and H) in female and male, exhibiting structural and functional abnormalities. 2. ProBNP and BPrisePME are not statistically different in the ASCVD. and FRS underestimates the risk for female. 3. Abnormal rise and elevated ProBNP can help in the identification of early CVD and risk stratification in asymptomatic subjects.

Trajectories of Vasomotor Symptoms and Carotid Intima Media Thickness in the Study of Women's Health Across the Nation.

Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women. The Study of Women's Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12. Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01], P=0.03) and greater maximal IMT (b [SE]=0.04 [0.01], P=0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors. This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction.

Abstract 15779: Quality of Life in a Cohort of Familial Hypercholesterolemia Patients Undergoing Molecular Cascade Screening in Brazil

Introduction:: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated disease associated with elevated risk of early cardiovascular disease (CVD) and thus can reduce quality of life. The present health related quality of life (HRQL) investigation, evaluated patients personal interpretation of morbidity burden in daily life. Methods: The study included a total of 1,032 adult individuals participating in a FH molecular cascade-screening program. The involved individuals were index cases (IC n=363), with genetic diagnosis or FH and their first-degree relatives (FDR, n=669). All patients were evaluated at the first session of the molecular diagnosis process. HRQL measurements, mental (MCS) and physical (PCS) component scores, was carried out with the Medical Outcomes Study (MOS) 12-Item Short-Form Health Survey (SF-12) questionnaire. Results: IC were older (52±13.1 vs. 46±16.2 years, P&lt;0.05) and presented lower PCS than FDR (44.7±9.3 vs. 49.2±8.4, P&lt;0.05). No differences were seen on the MCS component. Overall, generalized linear models showed that smoking habit (11.9% prevalence, P=0.006), previous diagnosis of hyperlipidemia (78.6%, P=0.020) and depression (13.5% prevalence, P&lt;0.000) were significant predictors of MCS. The presence of heart failure (6.5%, P=0.018), angina pectoris (12.9%, P=0.005), previous myocardial infarction (12.3%, P=0.012), hypertension (33.9%, P=0.018) and obesity (12.8%, P&lt;0.000) were all predictors of PCS. The presence of arrhythmias (10.7% prevalence) predicted both MCS and PCS (P=0.042 and P=0.00, respectively). Male gender (42.4%, P&lt;0.000) and education level (&lt; 9 years of background, 28% P&lt;0.000) were social-demographic aspects predictive of differences in MCS and PCS, respectively. Conclusions: Reductions in the individuals’ reported quality of life were explained by differences in social-demographic characteristics but mainly by inadequate health/disease status, such as risk factors and previous CVD. Active FH genetic cascade diagnosis by promoting early and adequate medical care and thus preventing early CVD, may improve substantially the subjective appraisal of HRQL.

Abstract 18819: Adverse Pregnancy Outcomes and Their Prediction of Future Heart Disease

Objective: Pregnancy provides an opportunity for a natural stress test, with the physiological demands of pregnancy acting as a maternal stress test that can predict a woman’s health later in life. The 2011 Update of the American Heart Association’s Evidence-Based Guidelines for the Prevention of Cardiovascular Disease in Women identifies many complications of pregnancy as relevant in the determination of cardiovascular disease (CVD) risk. This is important because CVD is the leading cause of death in women worldwide. The purpose of this research was to determine if, in our diverse inner city population, pregnancies complicated by hypertensive disorders, gestational diabetes, intrauterine growth restriction, or abruption were associated with future development of CVD. Methods: We identified women who delivered at a large, urban hospital in Bronx, NY from 1997-2001 who were treated for gestational diabetes, hypertensive disorders of pregnancy, intrauterine growth restriction, and placental abruption (n=183). A hospital database was used to identify our cohort and electronic medical records were reviewed to determine if these patients developed CVD over 10 years since the index pregnancy. The end points were subsequent Hypertension, Myocardial Infarction, Cerebrovascular disease, Type 2 Diabetes Mellitus, and Thromboembolic events. The cohort was compared to controls delivered at the same institution. Results: The relative risk (RR) of subsequent type 2 diabetes mellitus was 1.93 [CI 1.00-3.75], if the exposed population was older than 35 at the time of the index pregnancy. The RR of subsequent hypertension was 2.21 [CI 1.3-3.77] in African Americans at any age of index pregnancy, regardless of exposure. When comparing all exposed population to our controls; there is an increased risk in our population of CVD with a RR of 1.58 (CI 1.12-.2.23), and a p value of 0.01. Conclusions: In our large, diverse, urban population, age or the presence of preeclampsia were associated with an increased risk for adverse CVD. These women may be appropriate for early CVD risk screening and intervention at younger ages than previously identified. Women with adverse pregnancy outcomes should be targeted for risk factor modification and prevention programs.

Familial Hypercholesterolemia: new therapeutic approaches

Familial Hypercholesterolemia (FH) is caused by a mutation in the gene that encodes the low-density lipoprotein (LDL) receptor, resulting in very high levels of circulating LDL-cholesterol and endothelial damage during time. Apoprotein B, activated by LDL receptor, and PCSK9 (proprotein convertase subtilisin / kexin type 9 serine Protease), that impairs the clearance of LDL receptors, are important additional mechanisms that lead to increase LDL-cholesterol. The prevalence of Homozigous form (HoFH) is estimated to be 1 per 1 million individuals and, if untreated, proximal coronary disease or aortic valve disease frequently occurs during childhood and most affected patients suffer from fatal coronary disease before the age of 30. Heterozygous condition (HeFH) occurs in about 1/380-500 individuals. The levels of LDL-cholesterol in this form may greatly vary but the disease is always asymptomatic until adult age when there is a high risk of early cardiovascular disease. Lifestyle intervention and maximal statin therapy are the mainstays of treatment. In patients that not achieve LDL-C targets, primarly HoFH patients, adjunctive lipoprotein apheresis is recommended where available. Biological agents represents to date a new therapeutic approach for this not so rare condition. The PCSK9 pathway is one of the best examples of how genetics has led to identification of a new target for cholesterol management. Different PCSK9 inhibitors (alirocumab, evolocumab) are now available [1]. Mipomersen is an antisense oligonucleotide (ASO) that targets apoliporotein B-100 mRNA and disrupts its function: it is distributed mainly to the liver where it silences apoB mRNA, thereby reducing hepatic apoB-100 and giving rise to reductions in plasma total cholesterol, LDL-cholesterol, and apoB concentrations [2]. Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor. MTP resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B–containing lipoproteins in enterocytes and hepatocytes. This inhibition leads to a reduction in the synthesis of chylomicrons and very low–density lipoprotein, resulting in a reduction in plasma LDL levels [3].