Lower Incidence Of Cardiovascular Disease Research Articles

Fish oil consumption prevents ischemic injury through neovasculogenesis

Human endothelial progenitor cells (hEPCs) derived from bone marrow play a crucial in the prevention of ischemic injury in the course of postnatal neovasculogenesis. Frequent fish oil (FO) consumption is reportedly associated with a significantly lower incidence of cardiovascular disease (CVD). However, the molecular mechanisms of eicosapentaenoic acid (EPA) / docosahexaenoic acid (DHA) are not well elucidated, and the beneficial effect of FO consumption on neovasculogenesis has not been demonstrated yet. In the current study, we investigated the effects of EPA/DHA and FO consumption on neovasculogenesis both in vitro and in vivo. The results demonstrate that EPA /DHA dose‐dependently enhance the neovasculogenesis and cell migration of hEPCsin vitro. The mechanisms of action included upregulation of the c‐kit protein as well as the phosphorylation of the ERK1/2, Akt and endothelial nitric oxide synthase (eNOS) signaling molecules in hEPCs. Furthermore, EPA significantly suppressed the expression of microRNA (miR) 221 in vitro. In experimental animal models, FO consumption significantly induced the formation of new blood vessels (neovasculogenesis) and prevented ischemia. Taken together, it is suggested that FO consumption enhances neovasculogenesis mainly through the effects of EPA in hEPCs, thereby exerting a preventive effect against ischemic injury.

Obese-insulin resistance accelerates and aggravates cardiometabolic disorders and cardiac mitochondrial dysfunction in estrogen-deprived female rats.

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but have an increased incidence of CVD and metabolic syndrome after menopause, indicating the possible protective effects of estrogen on cardiometabolic function. Although obesity is known to increase CVD risks, its impact on the heart on estrogen deprivation is still inconclusive. We investigated the effects of obese-insulin resistance on cardiometabolic function in estrogen-deprived ovariectomized rats. Adult female ovariectomized (O) or sham (S)-operated rats randomly received either normal diet (ND, 19.77 % fat) or high-fat diet (HF, 57.60 % fat) (n = 6/group) for 12 weeks. The heart rate variability (HRV), left ventricular (LV) performance, cardiac autonomic balance, cardiac mitochondrial function, metabolic parameters, oxidative stress, and apoptotic markers were determined at 4, 8, and 12 weeks. Insulin resistance developed at week 8 in NDO, HFS, and HFO rats as indicated by increased plasma insulin and HOMA index. However, only HFO rats had elevated plasma cholesterol level at week 8, whereas HFS rats had showed elevation at week 12. In addition, only HFO rats had depressed HRV, impaired LV performance indicated by decreased fractional shortening (%FS) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, mitochondrial depolarization and swelling, as early as week 8, whereas other groups exhibited them at week 12. Either estrogen deprivation or obesity alone may impair metabolic parameters, cardiac autonomic balance, and LV and mitochondrial function. However, an obese insulin-resistant condition further accelerated and aggravated the development of these cardiometabolic impairments in estrogen-deprived rats.

Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice.

The consumption of flavan-3-ol-containing foods, including (-)-epicatechin (EC), has been linked to lower incidence of cardiovascular disease and stroke. We previously demonstrated nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) -dependent EC efficacy in reducing stroke-induced deficits in 2-mo-old mice; yet stroke is primarily a disease of the elderly. Because neuroinflammation, oxidative stress, and vascular dysfunction are hallmarks of aging, we tested whether Nrf2 mediates EC efficacy in aging mice through modulation of glial responses and blood brain barrier permeability. First, we compared anastomosis in naïve wild-type and C57BL/6 Nrf2(-/-) mice to identify potential differences in cerebrovascular architecture. Data showed no significant differences in the number of anastomoses or mean intersection points, indicating similar gross vascular physiology. To assess efficacy and mechanisms of protection, wild-type or Nrf2(-/-) mice were administered the minimum effective EC dose established in our previous studies before the permanent distal middle cerebral artery occlusion. Similar to previous results with young mice, 12-mo-old wild types also showed significant reductions in infarct volume (41.01 ± 29.57%) and improved performance in removing adhesive tape relative to vehicle-treated controls, whereas a trend toward protection was observed in Nrf2(-/-). However, EC did not reduce immunoreactivity for the microglia/macrophage marker anti-ionized calcium-binding adapter molecule 1, suggesting that dampened activation/recruitment did not account for EC protection. Furthermore, there were no differences in mouse IgG extravasation or spontaneous hemorrhage between EC-treated groups. These data demonstrate that EC protection occurs independent of microglia/macrophage modulation or blood brain barrier preservation, suggesting that the glial cell responses in young mice are compensatory to another, and potentially novel, protective mechanism.

Antioxidant Potentials of Tomato Paste Extracts Found on Major Markets in Accra Metropolis

The harmful effects of the free radicals on humans could be inhibited by antioxidants in fruits and vegetables. Tomato contains several antioxidants such as phenolic compounds and flavonoids. Consumption of tomatoes has been related epidemiologically to a lower incidence of cardiovascular diseases, prostate, gastrointestinal and epithelial cell cancers. In this study ten different brands of canned tomato pastes on the Ghanaian market were evaluated for their antioxidant potentials based on their polyphenolic and flavonoid contents as well as DPPH free radical scavenging activities. The amount of total phenolic compounds extracted were determined using the Folin-Ciocalteu reagent. Total flavonoid content was determined using aluminum chloride colorimetric assay method. The antioxidant activities were evaluated using the DPPH scavenging activity. Total phenolic and flavonoid contents ranged from 6.26 mg GAE/gdw to 22.82 mg GAE/gdw and between 1.83 μg QE/gdw to 45.26μg QE/gdw respectively. DPPH scavenging activity ranged from 8.03% to 29.69%. High and significant correlations existed between antioxidant activities, total phenolic and flavonoid contents of tomato paste samples analysed indicating these pastes are potentially rich sources of dietary polyphenolic compounds and antioxidants, and might contribute important health benefits to consumers.

The chromosome 9p21 variant interacts with vegetable and wine intake to influence the risk of cardiovascular disease: a population based cohort study.

BackgroundChromosome 9p21 variants are associated with cardiovascular disease (CVD) but not with any of its known risk markers. However, recent studies have suggested that the risk associated with 9p21 variation is modified by a prudent dietary pattern and smoking. We tested if the increased risk of CVD by the 9p21 single nucleotide polymorphism rs4977574 is modified by intakes of vegetables, fruits, alcohol, or wine, and if rs4977574 interacts with environmental factors on known CVD risk markers.MethodsMultivariable Cox regression analyses were performed in 23,949 individuals from the population-based prospective Malmö Diet and Cancer Study (MDCS), of whom 3,164 developed CVD during 15 years of follow-up. The rs4977574 variant (major allele: A; minor allele: G) was genotyped using TaqMan® Assay Design probes. Dietary data were collected at baseline using a modified diet history method. Cross-sectional analyses were performed in 4,828 MDCS participants with fasting blood levels of circulating risk factors measured at baseline.ResultsEach rs4977574 G allele was associated with a 16% increased incidence of CVD (95% confidence interval (CI), 1.10–1.22). Higher vegetable intake (hazard ratio (HR), 0.95 [CI: 0.91–0.996]), wine intake (HR, 0.91 [CI: 0.86–0.96]), and total alcohol consumption (HR, 0.92 [CI: 0.86–0.98]) were associated with lower CVD incidence. The increased CVD incidence by the G allele was restricted to individuals with medium or high vegetable intake (Pinteraction = 0.043), and to non- and low consumers of wine (Pinteraction = 0.029). Although rs4977574 did not associate with any known risk markers, stratification by vegetable intake and smoking suggested an interaction with rs4977574 on glycated hemoglobin and high-density lipoprotein cholesterol (Pinteraction = 0.015 and 0.049, respectively).ConclusionsOur results indicate that rs4977574 interacts with vegetable and wine intake to affect the incidence of CVD, and suggest that an interaction may exist between environmental risk factors and rs4977574 on known risk markers of CVD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0138-x) contains supplementary material, which is available to authorized users.

Functional foods and cardiometabolic diseases: International Task Force for Prevention of Cardiometabolic Diseases

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its very beginning, and additional research is necessary to substantiate the potential health benefit of foods for which the diet–health relationships are not yet scientifically validated. It appears essential, however, that before health claims are made for particular foods, in vivo randomized, double-blind, placebo-controlled trials of clinical end-points are necessary to establish clinical efficacy. Since there is need for research work aimed at devising personalized diet based on genetic make-up, it seems more than reasonable the latter be modeled, at present, on the Mediterranean diet, given the large body of evidence of its healthful effects.The Mediterranean diet is a nutritional model whose origins go back to the traditional diet adopted in European countries bordering the Mediterranean sea, namely central and southern Italy, Greece and Spain; these populations have a lower incidence of cardiovascular diseases than the North American ones, whose diet is characterized by high intake of animal fat. The meeting in Naples and this document both aim to focus on the changes in time in these two different models of dietary habits and their fall out on public health.

Variation in prescribing of lipid-lowering medication in primary care is associated with incidence of cardiovascular disease and all-cause mortality in people with screen-detected diabetes: findings from the ADDITION-Denmark trial.

AimsTo examine variation between general practices in the prescription of lipid-lowering treatment to people with screen-detected Type 2 diabetes, and associations with practice and participant characteristics and risk of cardiovascular events and all-cause mortality.MethodsObservational cohort analysis of data from 1533 people with screen-detected Type 2 diabetes aged 40–69 years from the ADDITION-Denmark study. One hundred and seventy-four general practices were cluster randomized to receive: (1) routine diabetes care according to national guidelines (623 individuals), or (2) intensive multifactorial target-driven management (910 individuals). Multivariable logistic regression was used to quantify the association between the proportion of individuals in each practice who redeemed prescriptions for lipid-lowering medication in the two years following diabetes diagnosis and a composite cardiovascular disease (CVD) outcome, adjusting for age, sex, prevalent chronic disease, baseline CVD risk factors, smoking and lipid-lowering medication, and follow-up time.ResultsThe proportion of individuals treated with lipid-lowering medication varied widely between practices (0–100%). There were 118 CVD events over 9431 person-years of follow-up. For the whole trial cohort, the risk of CVD was significantly higher in practices in the lowest compared with the highest quartile for prescribing lipid-lowering medication [adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6–7.3]. Similar trends were found for all-cause mortality.ConclusionsMore frequent prescription of lipid-lowering treatment was associated with a lower incidence of CVD and all-cause mortality. Improved understanding of factors underlying practice variation in prescribing may enable more frequent use of lipid-lowering treatment. The results highlight the benefits of intensive treatment of people with screen-detected diabetes (Clinical Trials Registry No; NCT 00237549).What's new Despite the well-established cardioprotective benefits of lipid-lowering treatment in Type 2 diabetes, evidence suggests large variations in statin use in primary care. Variation may be particularly high among people with screen-detected diabetes because general practitioners (GPs) might be reluctant to prescribe cardioprotective drugs for asymptomatic patients. There was wide variation in the prescription of lipid-lowering treatment among people with screen-detected diabetes in Danish primary care; more frequent prescription of lipid-lowering treatment was associated with a lower incidence of cardiovascular disease and all-cause mortality. More work is needed to improve understanding of the factors underlying practice variation in prescribing in order to encourage GPs to offer lipid-lowering treatment to this high-risk group.

Na+K+-ATPase activity and K+ channels differently contribute to vascular relaxation in male and female rats.

Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones’ effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K+) channels and Na+K+-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K+ channels and Na+K+-ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100 µM) and the following K+ channels blockers: tetraethylammonium (TEA, 2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 µM) and charybdotoxin (ChTX, 0.1 µM). The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K+ channel (Kv) participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax in females than in males. The functional activity of the Na+K+-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUAincubation. OUA reduced K+-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na+K+-ATPase functional activity. L-NAME reduced K+-induced relaxation only in the female group, suggesting that nitric oxide (NO) participates more in their functional Na+K+-ATPase activity. These results suggest that the K+ channels involved in the gender-based vascular relaxation differences are the large conductance Ca2+-activated K+ channels (BKCa) in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males.

Definitions and potential health benefits of the Mediterranean diet: views from experts around the world.

The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern.Electronic supplementary materialThe online version of this article (doi:10.1186/1741-7015-12-112) contains supplementary material, which is available to authorized users.

The health effects of US unemployment insurance policy: does income from unemployment benefits prevent cardiovascular disease?

ObjectivePrevious studies suggest that unemployment predicts increased cardiovascular disease (CVD) risk, but whether unemployment insurance programs mitigate this risk has not been assessed. Exploiting US state variations in unemployment insurance benefit programs, we tested the hypothesis that more generous benefits reduce CVD risk.MethodsCohort data came from 16,108 participants in the Health and Retirement Study (HRS) aged 50–65 at baseline interviewed from 1992 to 2010. Data on first and recurrent CVD diagnosis assessed through biennial interviews were linked to the generosity of unemployment benefit programmes in each state and year. Using state fixed-effect models, we assessed whether state changes in the generosity of unemployment benefits predicted CVD risk.ResultsStates with higher unemployment benefits had lower incidence of CVD, so that a 1% increase in benefits was associated with 18% lower odds of CVD (OR:0.82, 95%-CI:0.71–0.94). This association remained after introducing US census regional division fixed effects, but disappeared after introducing state fixed effects (OR:1.02, 95%-CI:0.79–1.31).This was consistent with the fact that unemployment was not associated with CVD risk in state-fixed effect models.ConclusionAlthough states with more generous unemployment benefits had lower CVD incidence, this appeared to be due to confounding by state-level characteristics. Possible explanations are the lack of short-term effects of unemployment on CVD risk. Future studies should assess whether benefits at earlier stages of the life-course influence long-term risk of CVD.

Loss-of-Function Mutations in APOC3 and Risk of Ischemic Vascular Disease

BackgroundHigh plasma levels of nonfasting triglycerides are associated with an increased risk of ischemic cardiovascular disease. Whether lifelong low levels of nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein C3 (APOC3) are associated with a reduced risk of ischemic cardiovascular disease in the general population is unknown.MethodsUsing data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease. Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10,797 participants, and ischemic heart disease developed in 7557 of these 10,797 participants.ResultsParticipants with nonfasting triglyceride levels of less than 1.00 mmol per liter (90 mg per deciliter) had a significantly lower incidence of cardiovascular disease than those with levels of 4.00 mmol per liter (350 mg per deciliter) or more (hazard ratio for ischemic vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss-of-function mutations in APOC3, as compared with no APOC3 mutations, was associated with a mean reduction in nonfasting triglyceride levels of 44% (P<0.001). The cumulative incidences of ischemic vascular disease and ischemic heart disease were reduced in heterozygotes as compared with noncarriers of APOC3 mutations (P=0.009 and P=0.05, respectively), with corresponding risk reductions of 41% (hazard ratio, 0.59; 95% CI, 0.41 to 0.86; P=0.007) and 36% (hazard ratio, 0.64; 95% CI, 0.41 to 0.99; P=0.04).ConclusionsLoss-of-function mutations in APOC3 were associated with low levels of triglycerides and a reduced risk of ischemic cardiovascular disease. (Funded by the European Union and others.)

Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways

Human endothelial progenitor cells (hEPCs) derived from bone marrow play a crucial in the prevention of ischemic injuries in the course of postnatal neovasculogenesis. Frequent fish oil (FO) consumption is reportedly associated with a significantly lower incidence of cardiovascular disease. However, the molecular mechanisms of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) are not well elucidated, and the beneficial effect of FO consumption on neovasculogenesis has not been demonstrated yet. In the current study, we investigated the effects of EPA/DHA and FO consumption on neovasculogenesis by using vascular tube formation assay, Western blotting, real-time polymerase chain reaction, immunohistochemical staining and Doppler imaging in both in vitro and in vivo models. The results demonstrate that EPA and DHA dose-dependently enhance the neovasculogenesis and cell migration of hEPCs in vitro. The mechanisms of action included up-regulation of the c-kit protein as well as the phosphorylation of the ERK1/2, Akt and endothelial nitric oxide synthase signaling molecules in hEPCs. Furthermore, EPA significantly suppressed the expression of microRNA 221 in vitro. In experimental animal models, FO consumption significantly induced the formation of new blood vessels (neovasculogenesis) and prevented ischemia. Taken together, it is suggested that FO consumption enhances neovasculogenesis mainly through the effects of EPA in hEPCs, thereby exerting a preventive effect against ischemic injury.

Sex hormones in the cardiovascular system.

Gender-associated differences in the development of cardiovascular diseases have been described in humans and animals. These differences could explain the low incidence of cardiovascular disease in women in the reproductive period, such as stroke, hypertension, and atherosclerosis. The cardiovascular protection observed in females has been attributed to the beneficial effects of estrogen on endothelial function. Besides estrogen, sex hormones are able to modulate blood pressure by acting on important systems as cardiovascular, renal, and neural. They can have complementary or antagonistic actions. For example, testosterone can raise blood pressure by stimulating the renin-angiotensin-aldosterone system, whereas estrogen alone or combined with progesterone has been associated with decreased blood pressure. The effects of testosterone in the development of cardiovascular disease are contradictory. Although some researchers suggest a positive effect, others indicate negative actions of testosterone. Estrogens physiologically stimulate the release of endothelium-derived vasodilator factors and inhibit the renin-angiotensin system. Although the cardioprotective effects of estrogen are widely appreciated, little is known about the effects of progesterone, which is commonly used in hormone replacement therapy. Progesterone has both vasodilatory and vasoconstrictive effects in the vasculature, depending on the location of the vessel and the level of exposure. Nevertheless, the mechanisms through which sex hormones modulate blood pressure have not been fully elucidated. Therefore, the characterization of those could lead to a better understanding of hypertension in women and men and perhaps to improved forms of therapy.

Exploiting the anti-inflammatory properties of olive (Olea europaea) in the sustainable production of functional food and neutraceuticals

Olive oil is an important lipid source of the Mediterranean diet which has been associated with lower incidence of cardiovascular diseases whereas olive pomace (OP), a natural by-product of olive oil production, has been found to contain micro constituents with antioxidant, antithrombotic and antiatherogenic activities. The evaluation of OP in order to produce sustainable functional food and neutraceuticals has been the subject of research over the last years. All recent data, focusing on the anti-inflammatory properties of olive oil derived from olive (Olea europaea) and OP along with the potential production of sustainable functional food and neutraceuticals, are presented in this review.

A whole grain diet reduces blood pressure in overweight/obese adults 151; a randomized control trial (249.3)

Epidemiological studies suggest that dietary whole grain intake is associated with a lower incidence of cardiovascular disease. However, there are no Level‐1 data from randomized control trials (RCT) to support these observations. We performed a double‐blind crossover RCT in 40 sedentary overweight/obese (39.1±1.1 years, BMI: 32.5±0.7 kg/m2) adults to test the hypothesis that a whole grain diet reduces cardiovascular risk. Diets were provided based on meeting nutritional guidelines for fat, protein and carbohydrate (i.e. ~28, 18, and 54%) and contained either whole grain (50 g/1000 kcal), or refined grain. Each diet was provided for 8 weeks with an 8‐10 week washout period between diets. A total of 33 subjects completed the study. Mean energy intake, based on resting metabolic rate and a sedentary lifestyle activity factor, was similar between the whole grain and refined grain diets (2051.4±60.7 and 2032.8±60.1 kcal/d, P=0.46). Diets were also similar in macronutrient intake, saturated fat, dietary cholesterol, sodium, and potassium. Compared to baseline, the whole grain and refined grain diets induced similar weight/fat loss (~2 kg, P&lt;0.05). Both diets reduced cholesterol, LDL cholesterol and triglycerides (all P&lt;0.05), but insulin was only reduced after the whole grain diet (P&lt;0.05). Although both diets reduced systolic blood pressure by ~3.5 mmHg, the improvement in diastolic blood pressure (‐5.9±1.1 vs. ‐2.3±1.4 mmHg, P&lt;0.05) and pulse pressure (2.6±2.1 vs. ‐2.5±1.6 mmHg, P&lt;0.05) was significantly greater after the whole grain compared to the refined grain diet. We conclude that a whole grain diet reduces cardiovascular risk factors and produces a clinically significant reduction in diastolic blood pressure in overweight/obese adults independent of weight loss. Since diastolic blood pressure is a predictor of mortality in adults under the age of 50 years, increased whole grain intake may provide a protective nutritional prevention and treatment strategy for hypertension.Grant Funding Source: A grant‐in‐aid from Nestle and NIH UL1‐RR024989

Hypoglycemic therapy in patients with type 2 diabetes and chronic heart failure

The article presents a literature review of prevalence, prognosis and treatment of overt tactics of chronic heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM). Application of modern pharmacological preparations and instrumental treatment of cardiovascular disease (CVD) increases life expectancy and improves the quality of life of patients with CHF as with normal carbohydrate metabolism (UO), and with type 2 diabetes. However, the risk of cardiovascular mortality (CAS) in patients with type 2 diabetes, compared to having a normal carbohydrate metabolism remains unchanged.Insulin resistance (IR) and compensatory hyperinsulinemia (GI) play a key role in the pathogenesis of type 2 diabetes. Ongoing research in the twentieth century of coronary heart disease (CHD) and heart failure in patients with type 2 diabetes revealed adverse effects of sulfonylurea medications on the metabolic processes in the myocardium and increased risk of death in patients with severe coronary artery disease. In comparison with sulfonylurea drugs, metformin and insulin not only reduces the risk of cardiovascular disease, but also can prevent or delay the development of type 2 diabetes in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose. Metformin acts on the key link of pathogenesis - insulin resistance, affecting the lower incidence of cardiovascular diseases, the development of chronic disease and mortality compared with insulin and sulfonylurea drugs. However, in patients with chronic heart failure is contraindicated the use of thiazolidinediones and metformin is limited tothe severity of CHF I-II FC NYNA. With effective treatment of chronic heart failure by cardiologists in patients with type 2 diabetes, affecting therapy with insulin resistance should be mandatory.

Abstract T P84: Beneficial Stroke Outcomes Following Epicatechin Consumption in Young and Older Mice

Background: The consumption of flavanol containing foods, including (-)-epicatechin, has been linked to lower incidence of cardiovascular disease and stroke. We have previously demonstrated that epicatechin prophylaxis reduces stroke-induced anatomical and functional deficits in young, healthy mice; yet clinical stroke is primarily a disease of the elderly. Since neuroinflammation and vascular dysfunction are associated with aging, we aimed to test whether epicatechin is also protective in aging mice subjected to experimental stroke, and if so, whether this results from reduced glial cell activation and blood brain barrier permeability. Methods: Twelve-month-old wildtype and C57BL/6 Nrf2 knockout mice were administered 15mg/kg epicatechin, the minimum effective dose in young, healthy mice, prior to permanent distal middle cerebral artery occlusion. Mice were evaluated for functional recovery at one day post-stroke using the Adhesive Removal Test. Infarct volume, gliosis, and blood brain barrier permeability estimates were conducted seven days following stroke. Additionally, we compared anastomosis in wildtype and Nrf2 knockout mice and assessed hemorrhage frequency in studies using four- and 12-month-old mice. Results: Consistent with previous results in young mice, 12-month-old wildtype mice pretreated with epicatechin showed significant reductions in infarct volume and latency to remove adhesive tape relative to vehicle-treated controls, while Nrf2 knockout mice were not protected by epicatechin. Interestingly, epicatechin did not reduce Iba1 immunoreactivity or mouse IgG extravasation at seven days post-stroke. Similarly, there were no significant differences in anastomosis or spontaneous hemorrhage between wildtype and Nrf2 knockouts, indicating that cerebral vascular physiology is similar and gross vascular integrity was unaffected by treatment. Conclusion: Thus, although epicatechin prophylaxis reduces infarct volume and functional deficits, it does not exert sustained effects on gliosis or cerebrovascular integrity in aging mice.

The Relationship Between Low-Density Lipoprotein Cholesterol Levels and the Incidence of Cardiovascular Disease in High-Risk Patients Treated With Pravastatin

This study aimed to evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular disease (CVD) in high-risk patients with hypercholesterolemia without a history of CVD. Patients who were receiving or started treatment with pravastatin, were followed-up for 2 years. Patients were divided into quartiles according to on-treatment LDL-C. The maximum contrast method based on the Cox proportional hazards model was used to evaluate the relationship between achieved LDL-C and the incidence of CVD. Incidence of CVD was also compared according to whether a number of risk factor targets were achieved. A total 6,229 patients were enrolled, with 4,916 having reported LDL-C values. During the 2 years, 69 cases of CVD (6.7/1000 patient years), including 36 coronary artery disease (CAD) (3.5/1000 patient years) and 28 strokes (2.7/1000 patient years), occurred. The comparison of on-treatment LDL-C level quartiles suggested that the incidence of all CVD decreased linearly as the LDL-C levels decreased. Incidence of CAD showed a curvilinear relationship to LDL-C levels, suggesting some attenuation of risk below LDL-C of 119 mg/dL. The incidence of all CVD and CAD tended to be decreased as the number of achieved risk factor targets increased. In conclusion, through our observational study, it was shown that a linear relationship between the incidence of CVD and LDL-C was observed in high-risk hypercholesterolemic patients. The low incidence of CVD in the present study may be associated with multifactorial management of conventional risk factors including high LDL-C levels. However, prospective, randomized studies are needed to confirm these findings.

Estrogen

See related article, p 616–623 Sex differences in the prevalence and progression of numerous cardiovascular diseases are well documented, with males typically exhibiting greater severity and progression of disease compared with age-matched females. In contrast, females are more likely to develop autoimmune disease compared with age-matched males, both clinically and experimentally. Nevertheless, there is growing evidence that certain autoimmune diseases, including systemic lupus erythematous (SLE), are associated with an increased risk of developing cardiovascular disease.1 Based on the expanding literature linking the immune system with cardiovascular disease, the question arises if females lose their cardiovascular protection with immune dysfunction and the molecular mechanisms driving cardiovascular disease in SLE. Historically, female sex hormones have been thought to contribute to the lower incidence of cardiovascular disease in premenopausal women. However, despite numerous studies designed to investigate the role of female sex hormones in cardiovascular disease, data from both animal and clinical research remain controversial. Therefore, it was with great interest that we read the study by Gilbert et al2 in the current issue of Hypertension , which was designed to determine whether estrogen has a causal role in the development of hypertension in adulthood in SLE, an autoimmune disease with high prevalence …

Leptin receptor Arg109 homozygotes display decreased total mortality as well as lower incidence of cardiovascular disease and related death

Two leptin receptor single nucleotide polymorphisms, Lys109Arg and Gln223Arg, have been shown to associate with several risk factors for cardiovascular disease. In addition, we have previously shown that Arg109 and Arg223 homozygotes displayed lower intima-media thickness in our well-defined OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. This current research investigated the impact of these LEPR polymorphisms on cardiovascular events and related death as well as to total mortality in the 19-year follow-up of OPERA. Subjects were randomly selected, middle-aged drug-treated hypertensives and their age- and sex-matched control subjects recruited to the OPERA study between 1990 and 1993. Mortality and hospital events of 1045 subjects were followed up until 2009. A total of 151 coronary heart disease (CHD) and 211 cardiovascular disease (CVD) events or deaths including 58 CHD and 69 CVD deaths occurred. Furthermore, during this follow-up, a total of 165 subjects died. Logistic regression analysis was performed to assess the impact of Lys109Arg and Gln223Arg on the events and death. Further modeling was performed with Cox regression for Lys109Arg. The logistic regression analysis revealed a significant protective impact of Arg109Arg genotype on CHD (OR 0.433; CI 95% 0.217–0.863) and CVD (OR 0.540; CI 95% 0.309–0.942) events or death as well as on total mortality (OR 0.390; CI 95% 0.196–0.775) when adjusted with age, sex and study group. Even after further adjustment with BMI, smoking status, systolic blood pressure and low-density lipoprotein cholesterol, the protective effect of Arg109Arg on CHD events or death and total mortality still remained statistically significant (OR 0.463; CI 95% 0.230–0.931 and OR 0.442; CI 95% 0.218–0.896, respectively). Arg109Arg was also shown to confer protection against CHD mortality (HR 0.224; CI95% 0.055–0.919) and overall mortality (HR 0.413; CI95% 0.218–0.783) also in Cox regression analysis. In conclusion, the Arg109Arg genotype of LEPR seems to be protective from cardiovascular events and death and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis.