BMC Cardiovascular Disorders - Latest articles

A compare between myocardial topical negative pressure levels of -25 mmHg and -50 mmHg in a porcine model

2008-06-22

Background: Topical negative pressure (TNP), widely used in wound care, is known to stimulate wound edge blood flow, granulation tissue formation, stimulation of angiogenesis and revascularization of the underlying tissue. We have previously shown that a myocardial TNP of -50 mmHg significantly increases microvascular blood flow in the underlying myocardium. We have also shown that a TNP pressure levels between -75 mmHg and -150 mmHg don't alter, or even have a tendency to decrease the microvascular blood in the underlying myocardium. The present study was designed to elucidate the difference between -25 mmHg and -50 mmHg TNP on microvascular flow in normal and ischemic myocardium. Methods: Six pigs underwent median sternotomy. The microvascular blood flow in the myocardium was recorded before and after the application of TNP using laser Doppler velocimetry. Analyses were performed before left anterior descending artery (LAD) occlusion (normal myocardium), and after 20 minutes of LAD occlusion (ischemic myocardium). Results: A TNP of -25 mmHg significantly increased microvascular blood flow in both normal (from 263.3 +/- 62.8 PU before, to 380.0 +/- 80.6 PU after TNP application, * p < 0.05) and ischemic myocardium (from 58.8 +/- 17.7 PU before, to 85.8 +/- 20.9 PU after TNP application, * p < 0.05). A TNP of -50 mmHg also significantly increased microvascular blood flow in both normal (from 174.2 +/- 20.8 PU before, to 240.0 +/- 34.4 PU after TNP application, * p < 0.05) and ischemic myocardium (from 44.5 +/- 14.0 PU before, to 106.2 +/- 26.6 PU after TNP application, * p < 0.05). Conclusions: Topical negative pressure of -25 mmHg and -50 mmHg both induce a significant increase in microvascular blood flow in normal and in ischemic myocardium.

Effect of garlic on blood pressure: A systematic review and meta-analysis

Karin Ried, Oliver R Frank, Nigel P Stocks, Peter Fakler and Thomas Sullivan — 2008-06-16

Background: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. Methods: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. Results: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). Conclusion: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.

The Metabolic Syndrome and the immediate antihypertensive effects of aerobic exercise: a randomized control design

2008-06-10

Background: The metabolic syndrome (Msyn) affects about 40% of those with hypertension. The Msyn and hypertension have a common pathophysiology. Exercise is recommended for their treatment, prevention and control. The influence of the Msyn on the antihypertensive effects of aerobic exercise is not known. We examined the influence of the Msyn on the blood pressure (BP) response following low (LIGHT, 40% peak oxygen consumption, VO2peak) and moderate (MODERATE, 60% VO2peak) intensity, aerobic exercise. Methods: Subjects were 46 men (44.3 ± 1.3 yr) with pre- to Stage 1 hypertension (145.5 ± 1.6/86.3 ± 1.2 mmHg) and borderline dyslipidemia. Men with Msyn (n = 18) had higher fasting insulin, triglycerides and homeostasis model assessment (HOMA) and lower high density lipoprotein than men without Msyn (n = 28) (p < 0.01). Subjects consumed a standard meal and 2 hr later completed one of three randomized experiments separated by 48 hr. The experiments were a non-exercise control session of seated rest and two cycle bouts (LIGHT and MODERATE). BP, insulin and glucose were measured before, during and after the 40 min experiments. Subjects left the laboratory wearing an ambulatory BP monitor for the remainder of the day. Repeated measure ANCOVA tested if BP, insulin and glucose differed over time among experiments in men without and with the Msyn with HOMA as a covariate. Multivariable regression analyses examined associations among BP, insulin, glucose and the Msyn. Results: Systolic BP (SBP) was reduced 8 mmHg (p < 0.05) and diastolic BP (DBP) 5 mmHg (p = 0.052) after LIGHT compared to non-exercise control over 9 hr among men without versus with Msyn. BP was not different after MODERATE versus non-exercise control between Msyn groups (p ≥ 0.05). The factors accounting for 17% of the SBP response after LIGHT were baseline SBP (β = -0.351, r2 = 0.123, p = 0.020), Msyn (β = 0.277, r2 = 0.077, p = 0.069), and HOMA (β = -0.124, r2 = 0.015, p = 0.424). Msyn (r2 = 0.096, p = 0.036) was the only significant correlate of the DBP response after LIGHT. Conclusion: Men without the Msyn respond more favorably to the antihypertensive effects of lower intensity, aerobic exercise than men with the Msyn. If future work confirms our findings, important new knowledge will be gained for the personalization of exercise prescriptions among those with hypertension and the Msyn.

The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

2008-05-27

Background: Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function. Methods: Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A2, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise. Results: Our results during exercise showed a) platelet activation (increased thromboxane B2, TXB2), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups). Conclusion: Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB2 levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.

A randomised trial of a 5 week, manual based, self-management programme for hypertension delivered in a cardiac patient club in Shanghai

Feng Xue, Wen Yao and Robert J Lewin — 2008-05-06

Background: In Shanghai there are 1.2 million people with hypertension, many of whom have difficulty in affording medical treatment. Community based, anti-hypertensive clubs have been created to provide health education but education alone is often ineffective. Lifestyle change programmes have shown some potential for reducing blood pressure but in previous trials have required specialist staff and extensive contact. We have previously demonstrated that self-management programmes delivered by health professionals, such as a nurse who has had short training in self-management techniques can change health behaviour and reduce symptoms. This study was designed to evaluate the benefits of a simple, cognitive-behavioural, self-management programme for hypertension based around a hypertension manual and delivered in the setting of a community anti-hypertensive club in Shanghai.MethodThe method was a pragmatic randomised controlled trial with an intention-to-treat analysis. Adult patients with mild-to-moderate primary hypertension, waiting to join a neighbourhood anti-hypertension club, were randomised to the self-management programme or to an information only control procedure. They attended the group treatment sessions on 4 occasions over 5 weeks for education combined with goal setting for lifestyle change and an introduction to exercise. The main outcome measures were: changes in blood pressure; blood total cholesterol; diet; activity level and health related quality of life 1 month and 4 months after the end of treatment. Results: A total of 140 adults with mild-to-moderate primary hypertension took part. All of the main outcomes showed beneficial changes. Four months after the end of treatment the mean blood pressure differences between groups were systolic 10.15 mm Hg (P < 0.001, 95% CI 7.25–13.05), and diastolic 8.29 mmHg (P < 0.001, 95% CI 6.71–9.88). Patients in the intervention group also had significantly reduced weight, lowered blood total cholesterol, increased physical activity and improved quality of life. Conclusion: Patients with mild-to-moderate primary hypertension attending a 5 week, group and manual based, cognitive-behavioural self-management programme, delivered through a voluntary club in Shanghai experienced a significant reduction in blood pressure.Trial registrationCurrent Controlled Trials ISRCTN73114566

Hypoxia-inducible factor-1alpha is a critical mediator of hypoxia induced apoptosis in cardiac H9c2 and kidney epithelial HK-2 cells

Ricky Malhotra, David W Tyson, Henry M Rosevear and Frank C Brosius — 2008-04-30

Background: Hypoxia inducible factor-1 (HIF-1) is a transcription factor that functions to maintain cellular homeostasis in response to hypoxia. There is evidence that HIF-1 can also trigger apoptosis, possibly when cellular responses are inadequate to meet energy demands under hypoxic conditions. Methods: Cardiac derived H9c2 and renal tubular epithelial HK-2 cells expressing either the wild type oxygen regulated subunit of HIF-1 (pcDNA3-Hif-1α) or a dominant negative version that lacked both DNA binding and transactivation domains (pcDNA3-DN-Hif-1α), were maintained in culture and exposed to hypoxia. An RNA interference approach was also employed to selectively knockdown expression of Hif-1α. Apoptosis was analyzed in both H9c2 and HK-2 cells by Hoechst and TUNEL staining, caspase 3 activity assays and activation of pro-apoptotic Bcl2 family member Bax. Results: Overexpression of pcDNA3-DN-Hif-1α led to a significant reduction in hypoxia -induced apoptosis (17 ± 2%, P < 0.01) in H9c2 cells compared to both control-transfected and wild type Hif-1α transfected cells. Moreover, selective ablation of HIF-1α protein expression by RNA interference in H9c2 cells led to 55% reduction of caspase 3 activity and 46% reduction in the number of apoptotic cells as determined by Hoechst 33258 staining, after hypoxia. Finally, upregulation of the pro-apoptotic protein, Bax, was found in H9c2 cells overexpressing full-length pcDNA3-HA-HIF-1α exposed to hypoxia. In HK-2 cells overexpression of wild-type Hif-1α led to a two-fold increase in Hif-1α levels during hypoxia. This resulted in a 3.4-fold increase in apoptotic cells and a concomitant increase in caspase 3 activity during hypoxia when compared to vector transfected control cells. HIF-1α also induced upregulation of Bax in HK-2 cells. In addition, introduction of dominant negative Hif-1α constructs in both H9c2 and HK-2 -cells led to decreased active Bax expression. Conclusion: These data demonstrate that HIF-1α is an important component of the apoptotic signaling machinery in the two cell types.

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care

2008-04-15

Background: Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS) in a very early stage. General practitioners (GPs), however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP), a biomarker that is detectable as soon as one hour after onset of ischemia. Methods: Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect®) in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG) and venapunction for a plasma troponin test within 12–36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result), using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis. Conclusion: Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP outside a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.

Rapid short-duration hypothermia with cold saline and endovascular cooling before reperfusion reduces microvascular obstruction and myocardial infarct size

2008-04-10

Background: The aim of this study was to evaluate the combination of a rapid intravenous infusion of cold saline and endovascular hypothermia in a closed chest pig infarct model. Methods: Pigs were randomized to pre-reperfusion hypothermia (n = 7), post-reperfusion hypothermia (n = 7) or normothermia (n = 5). A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min. Hypothermia was started after 25 min of ischemia or immediately after reperfusion by infusion of 1000 ml of 4°C saline and endovascular hypothermia. Area at risk was evaluated by in vivo SPECT. Infarct size was evaluated by ex vivo MRI. Results: Pre-reperfusion hypothermia reduced infarct size/area at risk by 43% (46 ± 8%) compared to post-reperfusion hypothermia (80 ± 6%, p < 0.05) and by 39% compared to normothermia (75 ± 5%, p < 0.05). Pre-reperfusion hypothermia infarctions were patchier in appearance with scattered islands of viable myocardium. Pre-reperfusion hypothermia abolished (0%, p < 0.001), and post-reperfusion hypothermia significantly reduced microvascular obstruction (10.3 ± 5%; p < 0.05), compared to normothermia: (30.2 ± 5%). Conclusion: Rapid hypothermia with cold saline and endovascular cooling before reperfusion reduces myocardial infarct size and microvascular obstruction. A novel finding is that hypothermia at the onset of reperfusion reduces microvascular obstruction without reducing myocardial infarct size. Intravenous administration of cold saline combined with endovascular hypothermia provides a method for a rapid induction of hypothermia suggesting a potential clinical application.

The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome

2008-03-17

Background: Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs) in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study). A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs. Methods: Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men) aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology. Results: Obesity (body mass index ≥ 30 kg/m2), smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment), dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels) and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment) were present in 947 (15.7%), 1673 (27.0%), 2268 (36.7%), 2113 (34.2%) and 407 (6.6%) of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age. Conclusion: The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.

WRN polymorphisms affect expression levels of plasminogen activator inhibitor type 1 in cultured fibroblasts

Elena Castro, Vladimir Oviedo-Rodríguez and Luis I Angel-Chávez — 2008-02-29

Background: Recessive mutations in WRN gene eliminate WRN protein function (helicase) and cause Werner syndrome. One of the most important clinical features of Werner syndrome patients are the premature onset and accelerated atherosclerosis process. Studies carried out on polymorphic WRN locus have shown that the alleles 1367R and 1074L confer protection for cardiovascular disease. Given that the levels of plasminogen activator inhibitor type 1 (PAI-1) were found to be significantly increased in Werner syndrome patients, is quiet possible that PAI-1 expression could be under regulation of WRN helicase. Therefore the purpose of this work was to evaluate the role of WRN polymorphism in modulating the expression of PAI-1. Methods: In order to accomplish our aim, an array of primary cultured fibroblasts from normal adult donors was genotyped for polymorphisms of both the WRN and PAI-1 loci. In addition, steady state levels of WRN and PAI-1 were measured by semi-quantitative RT-PCR assays in such cultures. To search for the potential relationship between the lack of WRN protein and PAI-1 expression, heterozygous cultures of fibroblasts (1367RC/1074LF; WRN genotype) were treated with a molecule of interference RNA against WRN messenger RNA (mRNA). Results: We found that, carriers of 1367R and 1074L alleles of WRN shown to have low amounts of PAI-1 in plasma (7.56 ± 5.02), as compared with carriers of 1367C and 1074F alleles (16.09 ± 6.03). Moreover, fibroblasts from carriers with these alleles had low expression levels of PAI-1 mRNA. The treatment of heterozygous primary fibroblast cultures (1367RC/1074LF; WRN genotype) with iRNA against WRN mRNA caused PAI-1 overexpression. Treatment with normal PAI-1 inducers (TGFβ, TNFα, or insulin) in these cultures and from those with genotypes 1367CC/1074FF and 1367RR/1074FL resulted in a genotype-dependent PAI-1 expression level. Conclusion: Our results suggest that polymorphisms in the WRN gene might have a significant role regulating PAI-1 levels in healthy individuals and "normal states" as well as acute or chronic stress, obesity, aging, acute inflammation, among others, where characteristic high levels of insulin, TNF α and TGFβ, could favor PAI-1 high levels in carriers with polymorphic variants (C and F alleles), beyond the levels reached by carriers with other alleles (R and L alleles).