Cardiovascular Disease Factors Research Articles

Breastfeeding and ApoB in late adolescence: a Hong Kong birth cohort study.

Breastfeeding may provide some population-level lifelong protection against cardiovascular disease. This study supports policies promoting breastfeeding as a modifiable exposure that contributes to a healthy start in life as an investment for lifelong cardiovascular disease prevention. • Apolipoprotein B (ApoB) is a recognizedrisk factor forcardiovascular disease, but whether breastfeeding affects ApoB in later life overall and by sex is unknown. • Exclusive breastfeeding in the first 3 months of life was associated with lower ApoB in late adolescence, with similar estimates for both sexes. • The inverse association of breastfeeding with ApoB suggests that breastfeeding could reduce cardiovascular disease and overall mortality over the lifespan.

MO468: Moving More Associates With Reduced Risk of Cardiovascular Disease and Death Across All Stages of Chronic Kidney Disease: A UK Biobank Study

Abstract BACKGROUND AND AIMS Physical activity (PA) is widely recommended for the prevention of chronic conditions including cardiovascular (CV) disease. In chronic kidney disease (CKD), it is unclear whether PA confers a similar benefit. We examined whether the duration and intensity of PA are associated with the risk of CV disease and mortality and whether the relationship differs in CKD. METHOD Participants were from UK Biobank: a prospective cohort study with over 500 000 participants. The estimated glomerular filtration rate was calculated using cystatin C (eGFRcys). CKD was defined according to the KDIGO guidelines and participants were categorized as no CKD (eGFRcys > 90mL/min/1.73m2), CKD G1-2 (eGFRcys 60–89mL/min/1.73m2) or CKD G3-5 (eGFRcys < 60mL/min/1.73m2). Exercise duration and intensity were self-reported using the international physical activity questionnaire (IPAQ) and participants were categorized into four groups: inactive (reference), low, moderate and vigorous PA, according to World Health Organisation (WHO) weekly PA recommendations. Cox proportional hazards models tested associations between PA category and a composite endpoint of CV disease (myocardial infarction or stroke) or all-cause mortality across CKD categories. Models were adjusted for other known risk factors for CV disease and death including age, smoking status, blood pressure, eGFRcys and albuminuria. RESULTS Of 502 460 participants in UK Biobank, 123 167 were excluded because of missing biochemistry or IPAQ data and a further 21 084 were excluded because of pre-existing CV disease: 358 209 participants were included in the analyses. Of these 182 457 (51.0%) were classed as no CKD, 162 621 (45.4%) as CKD G1-2 and 13 131 (3.7%) as CKD G3-5. A total of 48 369 (13.5%) of participants were classed as inactive and 211 591 (16.5%) as undertaking vigorous PA. In participants without CKD, any PA above inactivity was associated with a reduced risk of reaching the combined endpoint by approximately 20% (low: hazard ratio, HR 0.77, 95% confidence interval, CI 0.67–0.89; moderate: HR 0.80, 95%CI 0.70–0.91; vigorous: HR 0.81, 95%CI 0.73–0.90, P < 0.001). This relationship is maintained in CKD G1-2, but in CKD G3-5, moderate (HR 0.75, 95%CI 0.61–0.93) and vigorous (HR 0.77, CI 0.66–0.89, P < 0.001) activity are associated with reduced risk of the combined endpoint (Table 1). Interestingly across all categories of CKD, the majority of participants considered that they undertook more than the WHO minimum recommended PA per week. CONCLUSION Achieving the minimum weekly targets for PA set by WHO is associated with a significantly reduced risk of a combined endpoint of CV disease and death. This relationship is preserved in those with CKD G1-2, even when adjusted for other recognized risk factors. The benefit is seen in CKD G3-5 with increased intensity of PA, above the WHO minimum. PA data is self-reported which limits the accuracy and association does not prove causality. However, patients with CKD have a much higher risk of CVD and death and PA is a simple, low-cost intervention that warrants further study to improve CV morbidity and all-cause mortality amongst people with CKD.

Comparison of major adverse cardiovascular events risk after androgen deprivation therapy initiation by body mass index.

44 Background: The association between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients is controversial.1-2 Major adverse cardiovascular events (MACE) occurred in 3-6% of patients in a 48-week ADT trial,2 but meta-analysis from a 2011 study found no association between ADT and increased risk of CV death.1 Body mass index (BMI) is a potential risk factor; Lee et al. found a lower risk of MACE in patients with high BMI than those with a normal weight, and patients with low BMI had a higher risk of all-cause mortality.3 This study evaluates the association between BMI and MACE risk in PCa patients on ADT using real-world data. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=36,249) receiving LHRH agonist/antagonist injections were conducted to calculate the risk of MACE since ADT initiation for the following BMI groups: <18.5, 18.5 to <25, 25 to <30, 30 to <35, and >35. BMI groups were based on the standard weight status associated with each BMI range (underweight, normal or healthy weight, overweight, obese, and severely obese, respectively).4 The database contained 178,388 LHRH agonist/antagonist injection entries and 965 documented MACE events. Exclusion criteria included lack of ADT initiation date, lack of BMI data, and MACE within 6 months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause based on a recent study in this field.2 Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between BMI groups. Statistical significance between survival curves was evaluated by log-rank test. Results: Differences in MACE incidence between BMI groups were not significant. (Table). Conclusions: MACE risk was similar across BMI subgroups after ADT initiation. This is consistent with the literature that higher BMIs do not confer additional CV/MACE risk as might be expected (a lower risk of MACE in patients with high BMI than those with normal weight).3 This 10-year analysis in >35,000 patients is likely reflective of the real world, but further study is recommended to evaluate whether BMI should be considered a predisposing risk factor for CV disease in PCa patients undergoing ADT. As the association between ADT and increased CV risk in PCa patients is controversial, future studies evaluating the role of co-morbidities on MACE risk for PCa patients during ADT may be helpful to identify other CV predictors.[Table: see text]

Differences in hypercholesterolemia patient management in secondary and primary care: lessons learned from the German PROCYON survey

Abstract Background In Germany, cardiovascular (CV) disease was the leading cause of mortality (39% of all deaths), responsible for 340,000 deaths in 2014 (1). Considering its role as a major risk factor for CV disease, awareness for hypercholesterolemia in clinical practice seems insufficient. Purpose The purpose of the present survey was to identify patients' journey differences between primary and secondary prevention in patients with hypercholesterolemia. Methods PROCYON was a two-part online survey on disease perception, awareness, burden, and management of hypercholesterolemia consisting of a patient survey (PROCYON A) and a healthcare practitioner (HCP) survey (PROCYON B). The survey included over 5,000 patients with and without prior CV events as well as 109 HCPs (general practitioners, internists, cardiologists) involved in primary and secondary prevention. Results 71% of the HCPs consider low-density lipoprotein cholesterol (LDL-C) as “very important” to assess a patients CV risk and 96% acknowledge a “causal relationship” between CV risk and LDL-C levels. Despite the theoretical awareness of LDL-C as a risk factor, 58% of the secondary prevention patients were initially diagnosed with hypercholesterolemia only while hospitalized due to a CV event, indicating insufficient translation of LDL-C awareness into clinical screening routine. General practitioners (GP) and internists are the main point of contact for patients with hypercholesterolemia after the diagnosis. In primary and even in secondary prevention, cardiologists play a minor role in hypercholesterolemia patient care (cardiologist vs. GP/internist ratio 1:5), the majority of patients are managed by their general practitioners and internists and (cardiologist vs. GP/internist ratio 2:3) (Table 1). The frequency of LDL-C control assessments is lower in primary prevention patients compared to secondary prevention (Table 2). In primary prevention, only 43% of the patients are on a lipid lowering therapy compared to 87% in secondary prevention. From the point of diagnosis, LDL-C levels improved at least to some extent in only 30% of the primary prevention patients and 51% of the secondary prevention patients. Of the patients without LDL-C improvement who are on drug therapy, 53% (primary prevention) and 39% (the secondary prevention) are still on their initial treatment since diagnosis. Conclusion(s) Major differences in relation to assessment intervals, treatment initiation, and specialist care were identified between primary and secondary prevention populations, reflecting a major focus in secondary prevention with respect to primary prevention. The high percentage of patients on secondary prevention diagnosed after the first CV event reflects the need to improve preventive screening. It is essential to identify measures to increase LDL-C risk awareness, improve screening efforts and efficient LDL-C reduction in order to prevent future CV events in both populations. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma GmbH

Influence of cardiovascular drugs on the efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial

Abstract Background In DECLARE-TIMI 58, the sodium glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in a broad range of patients with type 2 diabetes mellitus (T2DM). SGLT2i are known to have diuretic and anti-hypertensive effects. However, whether concomitant CV drugs influence the efficacy and safety of dapagliflozin in these populations is less well known. Purpose We examined whether dapagliflozin consistently reduced the risk of CV outcomes and whether the safety of dapagliflozin was similar with or without the concurrent use of various CV drugs. Methods DECLARE–TIMI 58 was a randomized trial of dapagliflozin versus placebo in patients with T2DM and either atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for CV disease followed for a median of 4.2 years. We stratified patients by the use of CV drugs at baseline commonly used for heart failure: angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers (ACEi/ARB), beta-blockers, diuretics, and mineralocorticoid receptor antagonists (MRA). Efficacy outcomes of interest were the composite of CV death/HHF and HHF alone. We used the Cox proportional-hazard model for these analyses. Results Of 17,160 patients, 13,950 (81%) used ACEi/ARB, 9,030 (53%) used beta-blockers, 6,967 (41%) used diuretics, and 762 (4%) used MRA at baseline. All were balanced by randomized treatment groups. Patients using CV drugs at baseline had a greater prevalence of atherosclerotic risk factors and established CV disease than those without. Dapagliflozin consistently reduced the risk of CV death/HHF regardless of the use of CV medications (Figure). For HHF alone, similar results were seen with no significant interactions for any of the classes. There were no significant treatment interactions by the concomitant use of any of CV drugs for adverse events including symptoms of volume depletion or acute kidney injury. Conclusions In this analysis from the DECLARE–TIMI 58 trial, dapagliflozin consistently reduced the risk of CV death/HHF and HHF alone irrespective of the concurrent use of various CV drugs without any treatment interaction for key safety events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The DECLARE–TIMI 58 trial was supported by AstraZeneca.

The Roles of β-Carotene in Cardiomyocytes

Cardiovascular disease (CVD) is considered one of the major causes of mortality worldwide, with approximately 17.9 million deaths per year. There are several risk factors of cardiovascular diseases, such as behavioral factors (e.g., tobacco use, imbalanced diet, alcohol misuse, and lack of physical activities) and other underlying health-related factors (e.g., hypertension, dyslipidemia, and hyperglycemia). These factors are also correlated with the pathophysiology of CVD, and one of the determinants of early aging is the poor overall quality of life. One of the main strategies to prevent these risks is by achieving a healthy lifestyle, including the consumption of natural supplements. Recently, β -carotene has gained the attention of researchers owing to its natural antioxidant properties. It is found in fruit and vegetable compounds. In this article, we review the effects of β-carotene as an antioxidant that counteracts free radicals and cytoprotective agents that have positive benefits, such as preventing several age-related diseases improvement of the health of the cardiac muscle.

MALONDIALDEHYDE IN TYPE 2 DIABETICS AND ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS

Background: Type 2 diabetes mellitus (T2DM) is a progressive chronicdisease with high prevalence all over the world. It is expected to have 693million people affected by diabetes by 2045. Many body systems areaffected due to complications of DM with major effect on thecardiovascular system. Dyslipidemia is one of the major risk factors forcardiovascular disease in diabetes mellitus. Malondialdehyde (MDA) is ahighly toxic end product formed by lipid oxidation that mediates its toxiceffects due to its high reactivity particularly towards proteins and DNA.Malondialdehyde interacts both irreversibly and reversibly with proteinsand phospholipids causing profound effects, especially in the collagen ofthe cardiovascular system. Normally, MDA level remains within normalvalues due to antioxidant effects, but in DM these protective effects aredisrupted.Objective: Measure serum Malondialdehyde level as a marker of lipidperoxidation in type 2 diabetic patients and its association with othercardiovascular risk factors.Patients and methods: The study included 40 diabetic patients recruitedfrom Outpatient Diabetes Clinic at Alexandria Main University Hospitalin addition to healthy 40 healthy subjects as a control group. Basic data,clinical examination and laboratory analysis were obtained from all thesubjects within the two groups. Serum Malondialdehyde (MDA) wasmeasured in the participants within the two groups by using ELISA kit.Results: The mean serum MDA level was statistically significant higherin the diabetic cases as compared to the controls (Median MDA was30.72nmol /ml in cases and 25.16 nmol /ml in the control). There is asignificant increase in serum MDA level with increasing the risk of CVdisease in the whole study subjects and in the diabetic cases. In the casesgroup MDA shows positive correlation with all the study parametersexcept high density lipoproteins (HDL) where it revealed negativecorrelation. BY ROC curve analysis, a cutoff point more than > 26.57 had62.5% sensitivity, 70% specificity, 66.4 % positive predictive value (PPV)and 72.5% negative predictive value (NPV).Conclusion: Malondialdehyde is a non-invasive biomarker that could beutilized in differentiation of T2DM cases form healthy controls in additionfor identifying the high-risk diabetic patients for cardiovascular disease(CVD). However, further large-scale studies are recommended toaccurately determine its sensitivity and specificity.

Anti-Mullerian hormone concentrations are inversely associated with subclinical atherosclerosis in premenopausal women

Abstract Background Anti-Müllerian hormone (AMH) constitutes a marker of ovarian reserve and appears to have a predictive role regarding the time of menopause. Moreover, AMH is associated with adverse cardiac events. History of premature menopause and early onset of menopause have been associated with increased risk of cardiovascular (CV) disease. In addition, menopausal transition and duration of menopause have been associated with increased burden of subclinical atherosclerosis. However, the association between AMH as a marker of female reproductive age with atherosclerosis in premenopausal women is currently unknown. Purpose To investigate whether AMH concentrations are associated with markers of early atherosclerosis in healthy, normally menstruating women. Methods In a cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima-media thickness (IMT), lipid profile and serum AMH concentrations were assessed. Exclusion criteria were clinically overt CV disease, abnormal ovulatory cycles, polycystic ovarian syndrome, acute infection or chronic inflammatory disease, risk factors for CV disease and any medication Results Seventy premenopausal women, aged 32.7±6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or traditional CV risk factors was found. After multi-variable adjustment for traditional CV risk factors, the association between AMH concentrations combined IMT and carotid bulb IMT, remained significant. Conclusions In healthy, normally ovulating women, low AMH concentrations are associated with an adverse lipid profile and subclinical atherosclerosis, independently of traditional CV risk factors. This finding suggest a role of decreased follicular reserve with atherosclerotic disease. Funding Acknowledgement Type of funding source: None

1623-P: Prevalence and Clinical Determinants of Obesity in Type 1 Diabetes Mellitus

The prevalence of obesity in adults with type 1 diabetes mellitus (T1DM) is rising and is known to increase cardiovascular (CV) risk and mortality. However, the clinical features of adiposity are poorly described and discovery of novel associations may shed light on areas of possible intervention. We performed a retrospective cross-sectional analysis of 625 adults diagnosed with T1DM who were seen in Endocrinology between 2015-2018. These patients were stratified into 5 weight categories (normal weight, overweight, and obesity classes 1-3) then compared across various comorbidities, medication use, and metabolic parameters. Patients had a mean age of 35.2 ± 15.3 years, 53% were female, and >25% had a BMI ≥ 30. HbA1c did not significantly increase with weight. CV risk factors were more prevalent in patients with obesity (p<0.05) (Table 1). The anti-obesity medication, phentermine, was only prescribed in 3/172 patients and antidiabetic agents associated with weight loss were rarely applied to overweight individuals. Obesity combined with T1DM was associated with higher rates of metabolic disturbances and risk factors for CV disease. The sparse use of phentermine suggests suboptimal treatment of obesity in this population. Therefore, increased attention towards optimization of weight management for patients with obesity and T1DM is needed in an effort to reduce the comorbidities seen in this study. Disclosure Y. Tsushima: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc. K. Zhou: None.

A comparative study of lipid profile, creatinine, blood sugar and urine level among diabetic and obese population of western Gorakhpur

Modern life style is known to be responsible for sequence of manifestations like obesity and hyperlipedemia, hypercholesterolemia and atherosclerosis. Due to obesity, about 2.8 million people die every year worldwide. About 5% Indian were influenced by weight. This study includes 6Methodology for estimation of serum glucose 0 individuals, which includes 10 uncontrolled type-2 diabetic, 15 controlled type-2 diabetic, 15 obese and 20 healthy individuals. To study the lipid profile, creatinine, routine urine and fasting blood sugar for healthy, diabetic and obese subject various biochemical parameters like fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG), high density-lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), very low density lipoprotein cholesterol (VLDL-c), creatinine, and qualitative urine were analysis. In current study more numbers of patients with abnormal blood glucose and lipid profile found to belong to the age group of 30-60 years, 71% participants have abnormal blood glucose and lipid profile as compared to younger participants of age group 20-30 years, 6% younger participants have normal blood glucose and lipid profile. The present study clearly established that, diabetes along with obesity has a direct effect on the physiological functioning of liver and heart, which is proven by various tests. It is also noted that high consumption of fat results in the accumulation of fat in the body which can cause cardiovascular diseases. Diabetes along with obesity results increase in the concentration of cholesterol, triglyceride, LDL, VLDL and decrease in HDL, which are well established in the risk factor of cardiovascular disease. Keywords: Life style diseases, Serum creatinine, Serum cholesterol, Serum triglyceride.

Assessment of Metabolic Syndrome as a Risk Factorfor Cardiovascular Diseases in Tertiary Care Hospital in Northern Maharashtra

Assessment of Metabolic Syndrome as a Risk Factorfor Cardiovascular Diseases in Tertiary Care Hospital in Northern Maharashtra

Abstract 841: Loss of S-nitrosylation of G Protein-Coupled Receptor Kinase 2 Leads to Cardiovascular Dysfunction With Aging

Nitric oxide (NO) and S-nitrosothiol (SNO) have cardiovascular-protective properties and we have shown that one mechanism is through SNO-modification of G protein-coupled receptor (GPCR) kinase 2 (GRK2). S-nitrosylation at Cys340 (C340S) of GRK2 inhibits its activity on GPCRs such as β-adrenergic receptors in the heart and other GRK2 dependent processes. S-nitrosylation is believed to act as a brake on this pathological kinase. We generated global knock-in (KI) mice that express endogenous levels of GRK2, but with C340 mutated to Ser (GRK2-C340S). The C340 site is the primary site of S-nitrosylation and is largely responsible for eNOS-mediated cardioprotection after acute ischemic injury of the heart. In this study we observed that the loss of SNO-mediated inhibition of GRK2 leads to cardiovascular dysfunction during normal aging. GRK2 has been shown to be up-regulated during several cardiovascular (CV) pathologies including hypertension and heart failure, and aging is a major risk factor of CV disease (CVD). GRK2-C340S KI mice compared to their wild-type (WT) controls showed significant pathology as early as 52 weeks of age and was maintained up to 82 weeks. Maladaptive cardiac hypertrophy was present in aged GRK2-C340S mice with significant perivascular myocardial fibrosis. Fibrosis was prevalent in the kidneys as well. These histological changes were accompanied by reduced systolic function and pulse pressure compared to WT mice. Within the vasculature, aged GRK2-C340S aortas had reduced medial thickness and had reduced contraction in response to PE, KCl, or L-NAME. Acetylcholine-induced relaxation responses remained intact. Consistent with enhanced GRK2 activity in vivo in the heart, we found increased circulating levels of serum catecholamines. Many of these phenotypes we observed in GRK2-C340S mice are also observed in human aging and CVD. These phenotypes predispose patients to developing other diseases. As the US population becomes increasingly older, understanding the dynamic between aging and CVD is important in disease management and therapy. The aged GRK2-C340S mouse model represents a model of higher CVD risk and provides insights into consequences of chronic GRK2 global over-activity when the regulation of this kinase by NO is lost.

Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target.

Vascular calcification is a pathologic phenomenon consisting of calcium phosphate crystal deposition in the vascular walls. Vascular calcification has been found to be a risk factor for cardio-vascular diseases, due to its correlation with cardiovascular events and mortality, and it has been as-sociated with aging, diabetes, and chronic kidney disease.Studies of vascular calcification have focused on phosphate homeostasis, primarily on the important role of hyperphosphatemia. Moreover, vascular calcification has been associated with loss of plasma pyrophosphate, one of the main inhibitors of calcification, thus indicating the importance of the phos-phate/pyrophosphate ratio.Extracellular pyrophosphate can be synthesized from extracellular ATP by ecto-nucleotide pyrophos-phatase/phosphodiesterase, whereas pyrophosphate is hydrolyzed to phosphate by tissue-nonspecific alkaline phosphatase, contributing to the formation of hydroxyapatite crystals.Over the last decade, vascular calcification has been the subject of numerous reviews and studies, which have revealed new agents and activities that may aid in explaining the complex physiology of this condition. This review summarizes current knowledge about alkaline phosphatase and its role in the process of vascular calcification as a key regulator of the phosphate/pyrophosphate ratio.

A Hospital-based Study for Clinico-investigative Profile of Newly Diagnosed Patients of Hypothyroidism

Introduction: Hypothyroidism in adults has an insidious onset with a range of non-specific symptoms resulting in delayed diagnosis. Hypothyroidism is characterized by a broad clinical spectrum ranging from an overt state of myxedema, end-organ effects and multisystem failure to an asymptomatic or subclinical condition with normal levels of thyroxine and triiodothyronine and mildly elevated levels of serum thyrotropin. Thyroid dysfunction leads to altered glucose and lipid metabolism leading to insulin resistance, which is an important risk factor for cardio vascular diseases. This study attempts to study clinical and biochemical profile of patients with subclinical hypothyroidism or overt hypothyroidism. Aim of study: To study clinical and investigative profile of hypothyroidism in the newly diagnosed patients of hypothyroidism. Methods: All newly diagnosed hypothyroidism patients fulfilling inclusion and exclusion criteria were taken in to study. Demographic profile of all enrolled patients was recorded. They were subjected to detailed history and examination and the findings were recorded as a predesigned Performa. The clinical diagnosis of hypothyroidism was made as per Indian thyroid society guidelines. The following laboratory investigations were performed: serum lipid profile and serum uric acid using enzymatic assay, fasting insulin, creatinine, direct bilirubin, and the following liver function parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT). Thyroid-hormone profile, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), including anti-thyroid peroxidase (TPO). Observation and results: Between October 1, 2015 and September 30, 2016, 226 patients with newly diagnosed hypothyroidism were studied. Out of 226 patients, 48 patients excluded from the study. Central hypothyroidism was present in 4 patients and 44 were pregnant and lactating women. 178 patients with newly diagnosed hypothyroidism were enrolled in study. Out of 178 patients’ subclinical hypothyroidism was present in 29(16.9%) patients. Out of 178 patients, 131 (73.6%) were females and 47 (26.4%) were males and various parameters were studied. Conclusion: Our study confirms that dyslipidemia, insulin resistance and metabolic syndrome correlate positively with newly diagnosed hypothyroid patients.

The Influence of Obese Insulin-Resistance on the Outcome of the Ischemia/Reperfusion Insult to the Heart.

Obese insulin-resistance is one of the most important risk factor for cardiovascular diseases including ischemic heart disease (IHD). Growing evidences suggest that the susceptibility to myocardial ischemia-reperfusion (I/R) injury is increased in an obese insulin-resistance condition. Based on the currently available evidence from human and animal studies, this review mainly focuses on the influence of obese insulinresistance on the outcome of the I/R insult to the heart. Moreover, we have discussed whether improving insulin sensitivity by pharmacological interventions could ameliorate reperfusion induced myocardial injury. The electronic database Pubmed was used as the source of selected peerreviewed research articles published in English. Both pre-clinical studies and clinical trials were obtained using obesity, insulin resistance, ischemia-reperfusion injury and myocardial infarction as keywords. Twenty-seven pre-clinical studies were obtained using obesity, insulin resistance, and cardiac ischemia-reperfusion injury as keywords, and five clinical trials were obtained using obesity, insulin resistance, and myocardial infarction as keywords. The underlying mechanisms responsible for the exacerbation of I/R injury in obese insulinresistance were the main subject of our review. The findings of this review suggest that the susceptibility to I/R injury is increased in an obese insulin-resistance condition. However, the underlying mechanisms responsible for the exacerbation of I/R injury in obese insulin-resistance have not been fully elucidated, but increased basal oxidative stress, the impairment of anti-oxidant capacities, insulin signaling and pro-survival signaling and increased inflammation, likely play an important role.

Abstract P455: Obesity Types (Body Mass Index vs. Waist Circumference) Affect on Development of Major Cardiovascular Risks: Data From Korean National Health Insurance Service - National Sample Cohort (NHIS-NSC)

Background: Population based study demonstrated that obesity (defined as increased body mass index, BMI) is important predictor for developing hypertension and diabetes mellitus (DM), which have been well known major cardiovascular (CV) risk factors. Increased waist circumference (WC) representative of central obesity is focused as main factor for developing CV disease and its major risks. This study was to evaluate obesity as a predictor for new onset of hypertension and DM within 1-year in previously normotensives or normoglycemic subjects. Methods: The Korean National Health Insurance Service - National Sample Cohort (NHIS-NSC) established data about BMI and WC with medical, social and familial histories in 2009 and have been followed up for 1 years. Among total 349257 subjects with age more than 20 year-old, 95124 (normotensive group: 75.2% of population were 25-55 year-old, 54121(56.9%) male) of normotensives for evaluate new hypertension and 120501 (normoglycemic group: 83.6% of population were 25-65 year-old, 67183 (55.8%) male) normoglycemic subjects for evaluate new DM were analyzed. Results: During 1-year follow-up period, 3773 (3.97%) new hypertension in normotensive group and 1594 (1.32%) new DM in normoglycemic group were developed. Binary logistic regression analysis revealed that BMI was the predictor (Exp(B)=1.18, Sig<0.001) for new onset hypertension with age (Exp(B)=1.31, Sig<0.001), sex (Exp(B)=0.664, Sig<0.001), dyslipidemia and family history of hypertension. For new onset DM, WC (Exp(B)=1.04, Sig<0.001), age (Exp(B)=1.26, Sig<0.001), sex Exp(B)=0.664, Sig<0.001) and family history of DM (Exp(B)=1.76, Sig<0.001) were the independent predictors. Conclusion: Increase of BMI is independent predictor for new onset hypertension and increase of WC is independent predictor for new onset DM within 1-year. Obesity type might affects development of different major CV risks and hence, obesity itself is the important risk factor for CV disease.

Arterial stiffness in health and disease

The incidence of cardiovascular (CV) diseases is increasing worldwide raising the urgency for early detection of the underlying pathological processes. Early identification of risk factors is important to avoid hospitalization and to reduce CV morbidity and mortality rates. Cardiovascular risk can be assessed by history taking (age, gender, smoking habits), clinical examination (body mass index, heart rate, respiratory rate, blood pressure (BP), temperature and pulse oximetry), laboratory analysis (cholesterol, glucose, triglycerides, potassium, sodium) and with novel techniques like pulse wave velocity (PWV) and augmentation index. Pulse wave velocity is an emerging technique used for CV risk stratification, assessment of arterial stiffness and follow the efficiency of the therapeutic intervention. Pulse wave velocity proved to have independent predictive value when evaluated in conjunction with standard risk factors for CV diseases. However, the field of arterial stiffness research, which evolutes over the past 20 years, lacks guidance for research investigators. This review summarizes the mechanisms of arterial stiffness, various methodologies to assess arterial stiffness and the latest scientific statements regarding its clinical applications.

Abstract 13944: J Relationship of Body Mass Index of 22-year Cardiovascular Disease Mortality versus Body Mass Index

Introduction: J relationships of body mass index (BMI) with mortality have been described. However, little data are available on long-term follow-up in controlled clinical trials with respect to cardiovascular (CV) and all cause mortality. Hypothesis: We tested whether there is a J shape relationship between BMI with CV and all cause mortality at 22 years in the Systolic Hypertension in the Elderly Program (SHEP). Methods: SHEP was a placebo controlled, randomized clinical trial of antihypertensive therapy in patients with isolated systolic hypertension aged 60 and older. The relationship between CV and all cause mortality with baseline BMI was examined in 4,211 SHEP participants. Results: In unadjusted analyses, a J relationship was observed for all-cause mortality (linear term p=0.0318, quadratic term p=0.3217 and tricubic term p=0.0046) and for CV mortality (linear term p=0.0962, quadratic term p=0.6866 and tricubic term p=0.0908, left figure). The lowest risk was at a BMI of 25.9 for all-cause and 25.5 for CV mortality. The J shaped relationship between BMI and mortality was attenuated after adjustment for age, gender, comorbidities (e.g. diabetes, heart failure) and risk factors for CV disease (e.g. smoking and dyslipidemia, right figure). Age and gender were significant predictors of both all- cause and CV mortality: age p<0.0001, female gender p=0.0063 for all-cause mortality and p<0.0001 for age and p=0.0004 for female gender for CV mortality. <br/Conclusions: This study indicates that both very low and very high BMI are markers of high risk. The J relationship between BMI and mortality is mediated by age, female gender, comorbidities and risk factors for CV disease.

Possible Protective Mechanisms of Sitagliptin against Isoproternol Induced Myocardial Injury in Rat

Sitaglebtin, dipeptidyl peptidase 4 inhibitors, has been investigated and proved to improve triglycerides, low density lipoprotein and blood pressure, which are important risk factors for cardiovascular diseases. Aim: The present study was designed to investigate the potential protective effect of sitaglebtin in isoproterenol induced myocardial injury. Further assessment was done to address the cardioprotective mechanism. Method: Male Wister rats were treated with sitaglebtin (30 mg/kg/day for 2 weeks by gavage) and/ or isoproterenol (85mg /kg; i.p. 24 hours apart at day 14th and 15th of the experiment). Results: Isoproternol induced a significant ECG changes, several pathological changes and elevated cardiac enzymes. These changes were significantly attenuated by pre-treatment of rats with sitaglebtin. As a marker of oxidative stress, isoproterenol caused significant decrease in reduced glutathione level and superoxide dismutase with increase in malondialdhyde compared to the control group. Sitaglebtin pretreatment restored these markers toward normal values. Energy decline was assessed by measuring ATP/ADP, which decreased significantly in isoproterenol group and significantly increased by sitaglebtin pretreatment. Isoproternol caused inflammatory effects indicated by up-regulation of tumor necrosis factor-α expression in the myocardial tissue. Sitaglebtin also counteracted inflammatory cell infiltration, other histopathological changes, and the overexpression tumor necrosis factor-α in myocardial tissue. Collectively, these findings suggest that sitaglebtin, an anti-diabetic agent, has cardioprotective effect against isoproterenol induced myocardial injury that could be through antioxidant properties, TNF-α inhibition, and an enhancement of myocardial energy state .

Cardiovascular Benefits of Habitual Exercise in Systemic Lupus Erythematosus: A Review

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology that usually affects women of childbearing age. Although SLE causes damage to various body tissues, including joints, skin, kidneys, heart, lungs, blood vessels, and brain, cardiovascular (CV) disease is the leading cause of mortality and morbidity in this population. Because traditional risk factors for CV disease fail to completely explain the accelerated risk in patients with SLE, the management of CV disease is exceedingly difficult. Accumulating evidence indicates that regular exercise is beneficial in improving vascular function and disease-related symptoms associated with SLE. This can be accomplished with the intensity (mild), amount (moderate), and type (a variety) of physical activity that can be performed and tolerated by most, if not all, patients with SLE. However, the common signs and symptoms of SLE, including musculoskeletal problems, CV disease, and fatigue, are factors that are known to interfere with physical activity. Accordingly, the prescription of exercise needs to be conducted carefully for this population.