Female Cardiovascular Disease Research Articles

Abstract P314: A Community Outreach Program Focused on Hypertension Awareness Reaches 600+ People in Rural Georgia and Works to Build the Next Generation of Biomedical Scientists

The U.S. national average for the prevalence of hypertension in women aged 35-44 is 10.8%. In southeastern states including Georgia, Mississippi, and South Carolina, the prevalence of hypertension in women of this same age group is 13.5%, 17.8%, and 15.5%, respectively. The increase is mostly observed in Black women from non-metro areas. Thus, a need exists to improve awareness of cardiovascular risk in these communities and to support scientific research to improve the understanding of how sex contributes to differences in cardiovascular risk factors like hypertension. Rural Obese At Risk (ROAR) establishes a Specialized Center of Research Excellence on Sex Differences (SCORE) homed at Augusta University, spanning three Southeast universities. The overall goal is to establish ROAR as a national resource and recognized leader in cardiovascular disease in females, and to change perceptions and awareness surrounding cardiovascular risk in women across the Southeast, particularly in high-risk groups. One objective of ROAR Augusta is to establish a community outreach pipeline of trained scientists to increase awareness of sex as a biological variable (SABV), promote optimal cardiovascular healthcare for men and women, and empower the community to self-monitor and identify barriers to improving access to healthcare through the Community Engagement Core (CEC). The CEC aims to develop meaningful relationships among the research, medical, and lay communities promoting the increase of awareness of the importance of blood pressure control in women through community outreach, a Qualitative Needs Assessment, design and dissemination of unique illustrative educational materials related to cardiovascular disease in women, and the launch of a Blood Pressure Checks for Women campaign. In six months (December 2023 – May 2024), ROAR participated in 10 community events providing blood pressure checks and educational materials and reaching more than 600 people in 6 counties; awarded one pre-doctoral career enhancement mini-sabbatical; awarded three early career SABV pilot grants; hosted a SABV symposium reaching 120 biomedical scientists; and hosted a SABV seminar and workshop reaching 142 biomedical scientists. In conclusion, the ROAR CEC is well on its way to positively impacting hypertension perceptions and awareness in women across the Southeast.

Oral hormonal contraceptives and cardiovascular risks in females.

Oral hormonal contraception (OHC) is a widely employed method in females for the prevention of unintended pregnancies, as well as for the treatment of menstrual disorders, endometriosis, and polycystic ovarian syndrome. However, it is believed that with OHCs use, some females may have higher risk of cardiovascular diseases, such as hypertension, diabetes, myocardial infarction, thrombosis, and heart failure. Although such risks are infrequently detected in healthy young females with the use of oral contraceptives, slightly elevated risks of cardiovascular diseases have been observed among reproductive-aged healthy females. However, prolonged use of OHC has also been claimed to have protective cardiac effects and may contribute to reduced risk of cardiovascular disease. In fact, the debate on whether OHC administration increases the risk of cardiovascular diseases has been ongoing with inconsistent and controversial viewpoints. Nevertheless, a great deal of work has been carried out to understand the relationship between OHC use and the occurrence of cardiovascular risk in females who use OHC for preventing the unwanted pregnancy or treatment of other disorders. Therefore, in this review we summarize the most recent available evidence regarding the association between the use of oral hormonal contraceptives and the risk for cardiovascular disease in females who are using OHC to prevent unintended pregnancy.

Differential effects of cigarette smoking on cardiovascular disease in females: A narrative review and call to action

ObjectiveCigarette smoking continues to be a major driver in the incidence and progression of cardiovascular disease (CVD). As females become an increasingly larger fraction of those who smoke it is imperative that the sex-specific effects of smoking be further explored and acted upon. MethodsThis narrative review describes current evidence on the differential effects of smoking on CVD in females and the need to improve treatment. ResultsEvidence to date suggests that smoking has disproportionately negative effects on the cardiovascular (CV) system in females, especially in those who are younger. Usually, the onset of CVD is later in females than males, but smoking decreases or eliminates this gap. Females are also more likely to develop types of CVD closely tied to smoking, such as ST-elevated myocardial infarctions, with even higher rates among those who are younger. Possible mechanisms for these worse outcomes in females include a complex interplay between nicotine, other products of combusted cigarettes, and hormones. Sex differences also exist in treatment for smoking. In females, Varenicline appears more effective than either Bupropion or nicotine replacement therapy while in males, all three therapies show similar efficacy. Disparities in smoking are also apparent in secondary prevention settings. Females and males are entering secondary prevention with equal rates of smoking, with potentially higher levels of exposure to the byproducts of smoking in females. ConclusionsThese disproportionately negative outcomes for females who smoke require additional research and these persisting rates of smoking suggest a need for female-specific approaches for treating smoking.

Association of homocysteine with anaemia, menstrual cycle patterns, outcomes of pregnancy and risk for cardiovascular diseases in females from the Maldives National University

Association of homocysteine with anaemia, menstrual cycle patterns, outcomes of pregnancy and risk for cardiovascular diseases in females from the Maldives National University

Vaccination Coverage Against Human Papillomavirus in Female Students in Cyprus.

BackgroundHuman papillomavirus (HPV) has been associated with the development of several cancers and cardiovascular diseases in females. Nevertheless, there is still poor data on vaccination coverage against HPV in several countries, including Cyprus. The main target of the present research was to assess the vaccination status of female students in Cyprus.MethodologyAn online survey was conducted via a cloud-based short questionnaire on Google Forms. Students with a known email address were initially invited via email to complete the survey. The questionnaire was distributed to 340 students, aged 18-49 years old, who lived in Cyprus (60% response rate).ResultsThe total vaccination coverage was 38.1%. The mean age of participants was 23.5 (±6.5) years. The major reason for non-vaccination was the belief that participants were not at risk of serious illness from HPV infection (22%), followed by the reported lack of time to get vaccinated (16%) and inertia (13%). The students who had information about the safety of HPV vaccines from electronic sources of information (television, websites, and blogs) had lower vaccination coverage compared to those who had received information from alternative sources (primary health centers, family doctors, or obstetricians) (relative risk (RR) = 1.923, 95% confidence interval (CI) = 0.9669-3.825; p = 0.033). No significant differences in vaccination rates between participants who were coming from schools of health sciences versus those from financial schools (RR = 1.082, 95% CI = 0.7574-1.544; p = 0.3348) were observed.ConclusionsPublic health policy interventions and education on HPV vaccines are effective ways to improve the awareness and acceptance rate of HPV vaccination among female students and improve the HPV vaccination coverage level in Cyprus.

Cystamine reduces vascular stiffness in Western diet-fed female mice.

Consumption of diets high in fat, sugar, and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Women with obesity are more prone to develop arterial stiffening leading to more frequent and severe CVD compared with men. As tissue transglutaminase (TG2) has been implicated in vascular stiffening, our goal herein was to determine the efficacy of cystamine, a nonspecific TG2 inhibitor, at reducing vascular stiffness in female mice chronically fed a WD. Three experimental groups of female mice were created. One was fed regular chow diet (CD) for 43 wk starting at 4 wk of age. The second was fed a WD for the same 43 wk, whereas a third cohort was fed WD, but also received cystamine (216 mg/kg/day) in the drinking water during the last 8 wk on the diet (WD + C). All vascular stiffness parameters assessed, including aortic pulse wave velocity and the incremental modulus of elasticity of isolated femoral and mesenteric arteries, were significantly increased in WD- versus CD-fed mice, and reduced in WD + C versus WD-fed mice. These changes coincided with respectively augmented and diminished vascular wall collagen and F-actin content, with no associated effect in blood pressure. In cultured human vascular smooth muscle cells, cystamine reduced TG2 activity, F-actin:G-actin ratio, collagen compaction capacity, and cellular stiffness. We conclude that cystamine treatment represents an effective approach to reduce vascular stiffness in female mice in the setting of WD consumption, likely because of its TG2 inhibitory capacity.NEW & NOTEWORTHY This study evaluates the novel role of transglutaminase 2 (TG2) inhibition to directly treat vascular stiffness. Our data demonstrate that cystamine, a nonspecific TG2 inhibitor, improves vascular stiffness induced by a diet rich in fat, fructose, and salt. This research suggests that TG2 inhibition might bear therapeutic potential to reduce the disproportionate burden of cardiovascular disease in females in conditions of chronic overnutrition.

Abstract PS7-26: Acute myocardial infarction prevalence and trends in females with active breast cancer

Abstract Introduction:Breast cancer is among the three most common malignancies worldwide, and a better understanding of the epidemiology of the cardiovascular disease in females with breast cancer is needed Methods:Females with active breast cancer diagnosis hospitalized from January 2010 to December2017 were identified in the Nationwide Readmissions Database. Outcomes of interest were the prevalence of acute myocardial infarction (AMI), non-ST-segment myocardial infarction (NSTEMI), cardiac complications, and in-hospital mortality.Results:1,424,102 females with breast cancer were identified. Of whom, 17,578 (1.23%) were hospitalized for AMI. AMI patients were older with a mean age of 72.51 (11.73) vs. 62.22 (14.29), p<0.001. AMI patients had a higher prevalence of hypertension; 65.3% vs. 47.3%, p<0.001, known coronary artery disease; 51.1% vs. 8.2%, p<0.001, hyperlipidemia; 46.6% vs. 24.2%, p<0.001, known heart failure; 42.6% vs. 8.8%, p<0.001, smoking; 26.7% vs. 21.6%, p<0.001, history of stroke; 6.2% vs. 3.2%, p<0.001, history of prior AMI; 9.5% vs. 2.3%, p<0.001, and diabetes with chronic complications; 11.0% vs. 4.2%, p<0.001, and diabetes without complications; 25.2% vs. 15.8%, p<0.001. Over the 8 years, the prevalence of cardiovascular risk factors increased in breast cancer patients including; diabetes with chronic complications; from 2.3% in 2010 to 10.4% in 2017, p-trend<0.001, obesity; 7.8% in 2010 to 13.3% in 2017, p-trend<0.001, coronary artery disease; 8.1% in 2010 to 10.2% in 2017, p-trend<0.001, hyperlipidemia; 20.7% in 2010 to 29.7% in 2017, p-trend<0.001, and smoking; 16.8% in 2010 to 28.2% in 2017, p-trend<0.001. AMI increased over the study duration from 1.0% in 2010 to 1.8% in 2017, p-trend<0.001, and NSTEMI increased from 0.8% in 2010 to 1.5% in 2017, p-trend<0.001. The observed increase was persistent when patients with localized malignancies were examined with AMI inclining from 2.1% in 2010 to 2.4% in 2017, p-trend<0.001, and NSTEMI from 1.6% in 2010 to 2.0% in 2017, p-trend<0.001. Breast cancer patients with AMI had a higher hospital mortality rate; 14.7% vs. 4.2%, OR: 3.96, 95% CI (3.80-4.13), p<0.001, cardiac arrest; 3.9% vs. 0.5%, OR: 8.53, 95% CI (7.87-9.24), p<0.001, and cardiogenic shock, 5.1% vs. 0.1%, OR: 42.03, 95% CI (38.73-45.60), p<0.001.Conclusion:Females with breast cancer have a concerning prevalence of cardiovascular disease with stern worse outcomes, and the prevalence is shown to be increasing over the study duration. Known cardiovascular risk factors are also increasing in breast cancer patients. Further efforts should be directed to aggressively reduce the prevalence of modifiable risk factors in order to improve the outcomes of breast cancer patients. 20102011201220132014201520162017P-trendCoronary Artery Disease8.1%8.3%8.0%8.5%8.9%8.1%9.7%10.2%<0.001Diabetes with chronic complications2.3%2.5%2.5%2.9%3.3%3.9%7.2%10.4%<0.001Heart Failure7.8%7.8%7.9%8.5%9.5%9.0%11.3%12.5%<0.001Hyperlipidemia20.7%21.9%22.8%24.6%25.8%23.1%28.0%29.7%<0.001Obesity7.8%8.7%9.8%11.2%12.2%12.2%12.2%13.3%<0.001Smoking16.8%17.2%19.0%20.7%23.2%22.2%27.6%28.2%<0.001OutcomesAMIOverall1.0%1.0%1.1%1.1%1.3%1.2%1.5%1.8%<0.001Localized Malignancies2.1%1.9%2.0%2.0%2.1%1.8%2.0%2.4%<0.001Patients with History of Radiation Therapy1.2%0.7%1.1%0.7%1.2%1.2%1.6%1.6%<0.001History of prior AMI3.5%3.6%4.2%4.7%5.5%4.3%6.6%6.5%<0.001NSTEMIOverall0.8%0.8%0.9%0.9%1.0%1.0%1.3%1.5%<0.001Localized Malignancies1.6%1.5%1.6%1.6%1.7%1.5%1.7%2.0%<0.001Patients with History of Radiation Therapy0.9%0.6%0.9%0.6%0.9%1.0%1.5%1.3%<0.001History of prior AMI3.0%2.5%3.8%3.7%4.5%3.9%5.7%5.6%<0.001 Citation Format: Mohamed M Gad, Anas M Saad. Acute myocardial infarction prevalence and trends in females with active breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-26.

Comportamento em saúde e perfil nutricional de idosos hipertensos

Objetivo: avaliar o comportamento em saúde e o perfil nutricional de idosos hipertensos cadastrados no programa Hiperdia. Método: estudo transversal, realizado com 60 idosos hipertensos. Realizou-se a coleta de dados por meio de entrevista e avaliação antropométrica. Para a entrevista foi utilizado formulário semi-estruturado que englobou variáveis sociodemográficas e relacionadas ao comportamento em saúde entre o período de novembro e dezembro de 2017. Resultados: reportando-se aos hábitos alimentares, o alimento mais consumido foi a massa. O índice de etilismo e tabagismo foi baixo (8,3% e 13,3%) respectivamente. Em relação ao índice de massa corporal 53,0% dos idosos se apresentaram eutróficos, contudo, houve prevalência de obesidade abdominal, com risco elevado para doenças cardiovasculares no sexo feminino, (48,3%). Conclusão: a avaliação do comportamento em saúde e do estado nutricional de idosos hipertensos é crucial para a prevenção de complicações e surgimento comorbidades.

Mercury induces nuclear estrogen receptors to act as vasoconstrictors promoting endothelial denudation via the PI3K/Akt signaling pathway

Cardiovascular diseases (CVD) are more frequent among postmenopausal women due to the decline of estrogen concentration in plasma. However, the role of the vascular modulator effect of estrogen is controversial, since it occurs both in physiological and pathological conditions, increasing or reducing vascular reactivity. As mercury is widely associated with the development of CVD, we investigated putative hazardous effects on the mechanisms that modulate vascular reactivity in aortic rings of female Wistar rats promoted by acute mercury exposure. Mercury increased vascular reactivity and oxidative stress possibly due to NADPH oxidase participation, increased production of cyclooxygenase-2 (COX-2) and thromboxane A2 (TXA2) formation.The metal also induced endothelial denudation in the aorta by reducing the bioavailability of nitric oxide (NO) and enhancing the activity of the PI3K/Akt signaling pathway. Mercury exposure also induced nuclear estrogen receptors (ERα, ERβ) to act as vasoconstrictors. Our findings suggest that mercury might increase the chances of developing cardiovascular diseases in females and should be considered an important environmental risk factor.

Evaluation the effect of testosterone on the number of endothelial progenitor cells and amount of SDF-1α, PDGF, bFGF, and NO.

Background:Recent therapeutic advances in cardiovascular disease, thanks to the discovery of endothelial progenitor cells (EPCs). Stromal cell-derived factor-1α (SDF-1α), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and nitric oxide (NO) play a role in migration, homing, and differentiation of EPCs into mature endothelial cells. The incidence of cardiovascular disease is higher in men than in women. This fact suggests the influence of sex hormones on incidence of cardiovascular disease.Methods:Twenty-four female wistar rats weighing 160–180 g were randomly divided into four groups (N = 6): 1. sham-treated by sesame oil, 2. ovariectomized (OVX)-treated by sesame oil, 3. OVX-treated by 10 μg/kg/day testosterone, and 4. OVX-treated by 100 μg/kg/day testosterone. After 21 days, the animals were euthanized and blood samples were saved for determination of EPC count and serum levels of SDF-1α, PDGF, bFGF, and NO production.Results:High-dose testosterone induced significant increase in EPC count in OVX rats (P < 0.05). Also 100 μg/kg/day testosterone increased serum level of SDF-1α more than OVX-treated by 10 μg/kg/day testosterone (P < 0.05). But 10 μg/kg/day testosterone increased significantly the serum level of PDGF >100 μg/kg/day testosterone-treated group (P < 0.05). The serum level of bFGF in sham-treated by sesame oil was equal with its concentration in OVX-treated by 100 μg/kg/day testosterone. And the serum concentration of NO production in testosterone-treated groups were significantly less than other groups (P < 0.05).Conclusions:This study suggests that testosterone might be effective on cardiovascular disease in females by increasing EPC count through SDF-1α and PDGF mechanisms which are some of the vascular healing factors.

Abstract 096: Progesterone Upregulates Endothelial Mineralocorticoid Receptor Expression Which Predisposes Female Mice to Obesity-Induced Endothelial Dysfunction

Compelling evidence indicates a higher efficacy of mineralocorticoid receptor (MR) blockade for the treatment of cardiovascular disease in females with obesity and diabetes than in males, however, the origin of this sex-specific effect is unknown. We have shown that leptin induces endothelial dysfunction in obese female mice via aldosterone-dependent activation of MR and that only female mice develop endothelial dysfunction (vasorelaxation to acetylcholine) in response to aldosterone ex vivo . Therefore, we hypothesized that females express higher endothelial MR (ECMR) expression than males which predisposes females to obesity-associated endothelial dysfunction. RT-PCR analysis in isolated aortic endothelial cells of Balb/C mice revealed a higher NR3C2 (MR gene) expression in females compared to males (2.9±0.5-fold from male, P&lt;0.05), however, no such difference was observed in non-endothelial cells. Similarly, human adipose tissue endothelial cells exhibited higher ECMR mRNA expression than males (2.1±0.1 fold from male). Female sex-hormone suppression (ovariectomy) decreased ECMR expression in female mice (-0.8±0.2-fold from sham), which was restored by progesterone supplementation (-0.1±0.1-fold from sham). NR3C2 mRNA gradually increased with progesterone in diestrous (1.6±0.1-fold from estrous) phase and increased further in pregnancy day 16 (9.2±0.2-fold from estrous). Furthermore, progesterone dose-dependently increased ECMR protein expression in human endothelial cells in vitro (P&lt;0.05). Increases in ECMR associated with higher progesterone levels in diestrus and pregnant females were associated with an increased sensitivity to leptin-induced endothelial dysfunction in mice. In parallel, while leptin induced endothelial dysfunction in intact ECMR female mice (P&lt;0.05), specific deletion of MR in endothelial cells protected female mice from leptin-induced endothelial dysfunction. These data indicate that progesterone drives the sex-difference in the levels of ECMR expression and predisposes female mice to leptin-induced endothelial dysfunction. In addition, these data provide a rational for the higher efficacy of MR blockade in obese and diabetic women suffering from cardiovascular disease.

Mineralocorticoids and Cardiovascular Disease in Females with Insulin Resistance and Obesity.

In the present review, we will discuss the evidence and the mechanisms underlying the complex interplay between obesity, mineralocorticoid receptor activation, and cardiovascular dysfunction with special emphasis on the pathogenesis of cardiovascular disease (CVD) in obese and insulin-resistant females. Since the initial isolation of aldosterone in 1953 and the cloning of the mineralocorticoid receptor (MR) decades later, our understanding has expanded tremendously regarding their involvement in the pathogenesis of CVD. Recent results from both pre-clinical and clinical studies support a close correlation between increase adiposity and enhanced aldosterone production (MR activation). Importantly, insulin resistance and obese females are more prone to the deleterious cardiovascular effects of MR activation, and enhanced MR activation in females has emerged as an important causative event in the genesis of a more severe CVD in diabetic women. Different clinical trials have been completed examining the effect of MR blockade in subjects with CVD. Despite its important beneficial mortality impact, side effects are frequent and a newer MR antagonist, finerenone, with less risk of hyperkalemia is currently being tested in large clinical trials.

Oxidative injuries induced by maternal low-protein diet in female brainstem

Many studies have shown that a maternal low-protein diet increases the susceptibility of offspring to cardiovascular disease in later-life. Moreover, a lower incidence of cardiovascular disease in females than in males is understood to be largely due to the protective effect of high levels of estrogens throughout a woman's reproductive life. However, to our knowledge, the role of estradiol in moderating the later-life susceptibility of offspring of nutrient-deprived mothers to cardiovascular disease is not fully understood. The present study is aimed at investigating whether oxidative stress in the brainstem caused by a maternal low-protein diet administered during a critical period of fetal/neonatal brain development (i.e during gestation and lactation) is affected by estradiol levels. Female Wistar rat offspring were divided into four groups according to their mothers’ diets and to the serum estradiol levels of the offspring at the time of testing: (1) 22 days of age/control diet: (2) 22 days of age/low-protein diet; (3) 122 days of age/control diet: (4) 122 days of age/low-protein diet. Undernutrition in the context of low serum estradiol compared to undernutrition in a higher estradiol context resulted in increased levels of oxidative stress biomarkers and a reduction in enzymatic and non-enzymatic antioxidant defenses. Total global oxy-score showed oxidative damage in 22-day-old rats whose mothers had received a low-protein diet. In the 122-day-old group, we observed a decrease in oxidative stress biomarkers, increased enzymatic antioxidant activity, and a positive oxy-score when compared to control. We conclude from these results that following a protein deficiency in the maternal diet during early development of the offspring, estrogens present at high levels at reproductive age may confer resistance to the oxidative damage in the brainstem that is very apparent in pre-pubertal rats.

Paraoxonases-1, -2 and -3: What are their functions?

Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual’s functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa’s pathogenesis. All three PONs modulate oxidative stress and inflammation. PON2 is localized in the mitochondria and endoplasmic reticulum. PON2 has potent antioxidant properties and is found at 3- to 4-fold higher levels in females than males, providing increased protection against oxidative stress, as observed in primary cultures of neurons and astrocytes from female mice compared with male mice. The higher levels of PON2 in females may explain the lower frequency of neurological and cardiovascular diseases in females and the ability to identify males but not females with Parkinson’s disease using a special PON1 status assay. Less is known about PON3; however, recent experiments with PON3 knockout mice show them to be susceptible to obesity, gallstone formation and atherosclerosis. Like PONs 1 and 2, PON3 also appears to modulate oxidative stress. It is localized in the endoplasmic reticulum, mitochondria and on HDL. Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis.

A cross-sectional study on effect of body mass index on the spectral analysis of heart rate variability

Background: Obesity is associated with dysregulation of autonomic function. Heart rate variability (HRV) in women has been related independently to menstrual cycle, body mass index (BMI), and other factors. A reduced HRV is associated with autonomic dysregulation. Aims and Objectives: The study was undertaken to observe the effect of BMI on the analysis of HRV in young adult females. Materials and Method: A total of 60 healthy women aged 18–30 years participated in the study. Their BMI was measured after recording their height and weight using Quetelet’s index. The HRV recording of each subject was then done. Using appropriate statistical tests, the HRV was compared among the subjects of different BMI groups. Result: HRV is reduced in overweight females depicted by an increase in low frequency (LF) and low frequency / high frequency ratio in overweight females when compared to normal-weight females. Conclusion: Raised BMI is associated with reduced HRV correlates with sympathetic overactivity and sympathovagal imbalance thereby increasing the chances of cardiac autonomic dysfunction, ultimately leading to cardiovascular disease in females.

OP22 The impact of estrogen on the anti-atherogenic effect of H2S

Objective Both estrogen and hydrogen sulfide (H 2 S) are involved in the regulation of atherosclerosis development. We previously reported that male mice with cystathionine gamma-lyase (CSE) gene knockout (CSE-KO) exhibited reduced vascular H 2 S production and increased adhesion molecule expression, which led to early development of atherosclerosis. Estrogen offers significant protection against proliferative cardiovascular diseases in females. The objective of this study is to investigate the impact of estrogen on the anti-atherogenic effect of H 2 S. Methods and results Plasma estrogen (17 β -estradiol) levels were significantly decreased in female CSE-KO mice in comparison with female wild-type (WT) mice. Age-matched female CSE-KO and WT mice were fed with control or atherogenic diet for 12-weeks. Plasma lipid levels, except triglyceride levels, were significantly increased in atherogenic diet-fed WT and CSE-KO mice when compared with control diet-fed groups. However, the extent of lipid change was greater in CSE-KO mice than in WT mice. Atherogenic diet fed female CSE-KO mice, but not WT mice, developed early atherosclerotic lesion. Atherogenic diet induced more atherosclerotic lesion, oxidative stress and intra-cellular adhesion molecule-1 (ICAM-1) expression and nuclear factor kappa B (NF κ B) pathway in female CSE-KO mice when compared with female WT mice. To explore the role of estrogen in early development of atherosclerosis, female WT and CSE-KO mice fed with atherogenic diet were administered subcutaneously with 17 β -estradiol at 80 μg/kg/day for 12 weeks. This treatment suppressed atherogenic factors such as hypercholesterolemia, oxidative stress, ICAM-1 expression and NF κ B pathway in female WT mice, but not in female CSE-KO mice. Conclusions Deficiency of CSE/H 2 S pathway lowered plasma estrogen levels in female mice and nullified the effects of estrogen on hypercholesterolemia, oxidative stress, ICAM-1 expression and atherosclerosis development. Thus, H 2 S is irreplaceable for these vascular effects of estrogen. The impact of this H 2 S dependency of estrogen on atherosclerosis development and the underlying mechanisms remain to be clarified.

Acetylcholinesterase activity in selected regions of the rat brain following paraoxon intoxication and concurrent therapy

Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual’s functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa’s pathogenesis. All three PONs modulate oxidative stress and inflammation. PON2 is localized in the mitochondria and endoplasmic reticulum. PON2 has potent antioxidant properties and is found at 3- to 4-fold higher levels in females than males, providing increased protection against oxidative stress, as observed in primary cultures of neurons and astrocytes from female mice compared with male mice. The higher levels of PON2 in females may explain the lower frequency of neurological and cardiovascular diseases in females and the ability to identify males but not females with Parkinson’s disease using a special PON1 status assay. Less is known about PON3; however, recent experiments with PON3 knockout mice show them to be susceptible to obesity, gallstone formation and atherosclerosis. Like PONs 1 and 2, PON3 also appears to modulate oxidative stress. It is localized in the endoplasmic reticulum, mitochondria and on HDL. Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis.

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program

BackgroundThe Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years.MethodsThis study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics.ResultsAmong the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects.ConclusionThe prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.

Lipid Profile of Type 2 Diabetic and Hypertensive Patients in the Jamaican Population

Aims:Previous studies have shown that diabetes mellitus (DM) increases the risk of cardiovascular diseases in females to a greater extent than in males. In this cross-sectional study, we evaluated the lipid profiles of type 2 diabetic males and females.Materials and Methods:The study included 107 type 2 diabetic patients (41 males and 66 females), and 122 hypertensive type 2 diabetic patients (39 males and 83 females), aged 15 years and older. Total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and high density lipoprotein-cholesterol (HDL-C) concentrations were assayed for each group using standard biochemical methods.Results:The mean TC, TG, VLDL-C, HDL-C and LDL-C concentrations, TG/HDL and LDL/HDL ratios were higher in type 2 diabetic and hypertensive type 2 diabetic patients compared with non-diabetic, and hypertensive non-diabetic control subjects, although these were not significant (P > 0.05). Hypertensive type 2 diabetic females had significantly higher serum TC (7.42 ± 1.63 mmol/L) than hypertensive non-diabetic males (5.76±1.57 mmol/L; P < 0.05). All the other lipid and lipoprotein parameters except HDL-C were non-significantly higher in females with type 2 DM and those with hypertension and type 2 DM, compared with type 2 diabetic and hypertensive type 2 diabetic males, respectively (P > 0.05).Conclusion:This study demonstrated that dyslipidemia exists in our type 2 diabetic population with greater TC in hypertensive type 2 diabetic females compared with hypertensive type 2 diabetic males. This suggests that hypertensive type 2 diabetic females are exposed more profoundly to risk factors including atherogenic dyslipidemia compared with males.

Regional life expectancy patterns in Lithuania

Background: The objective of this study was to investigate levels and trends of inequalities in life expectancy in administrative regions of Llthuania during 1988–1996 and to analyse possible reasons for reglonal inequalities. Methods: Information about the population and the deceased was obtained from the Lithuanian Department of Statistics. Life tables of 55 administrative regions of Lithuania were compiled in 3 year intervals: 1988–1990, 1991–1993 and 1994–1996. The contribution of major causes of death to regional inequalities in life expectancy was assessed. Associations of the regional inequalities in life expectancy with the level of urbanisation, health care resources, level of education, marital status, and unemployment along with certain indicators of well-being were evaluated. Results: The life expectancy of males varied by 7.4–10.8 years and that of females by 5.6–7.2 years in different regions. The more favourable regions for both males and females were the major towns and the resort town of Druskininkai. Differences in mortality from external causes of death in males and cardiovascular diseases in females contributed most significantly to the regional inequalities in life expectancy. Inequalities correlated with the regional differences in the level of urbanisation, education and marital status. There were no associations observed with either the distribution of health care resources, level of unemployment or certain other economic aspects of well-being. Conclusions: Large-scale, individual-based data would need to be studied to explain the considerable regional inequalities in life expectancy and for equity-oriented policy and strategy application.