Risk Of Acute Cardiovascular Events Research Articles

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

ObjectivesPrevious studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates...

Serum uric acid levels during dual antiplatelet therapy with ticagrelor or clopidogrel: Results from a single-centre study

Background and aimsNew antithrombotic therapies have significantly improved the outcomes of patients with acute coronary syndrome (ACS), where the introduction of ticagrelor has provided the greatest mortality benefits. However, ticagrelor treatment has been associated with a potential increase in the serum uric acid (SUA) levels, which may influence endothelial dysfunction and prothrombotic status, thereby affecting the risk of acute cardiovascular events in patients requiring dual antiplatelet therapy (DAPT). The present study aimed to compare the impact of antiplatelet agents such as ticagrelor or clopidogrel on SUA levels and their effect on platelet reactivity. Methods and resultsWe included patients admitted for ACS or elective percutaneous coronary intervention (PCI) and discharged with ASA (acetylsalicylic acid; 100–160 mg) and clopidogrel (75 mg) or ticagrelor (90 mg twice a day). Chemistry was assessed at admission (baseline) and after a 30–90-day period of DAPT (together with platelet reactivity). The absolute and percentage variations of SUA after DAPT introduction were considered. Multiple-electrode aggregometry was used to assess platelet function.A total of 378 patients were enrolled, with 145 treated with aspirin and clopidogrel (AC) and 233 with aspirin and ticagrelor (AT). The AC patients were older (p = 0.003) and more often showed elective PCI as an indication to DAPT (<0.001); they received chronic therapy with ARB (angiotensin II receptor blocker; p = 0.001), nitrates (p = 0.044), CCB (calcium channel blocker; p = 0.005) and diuretics (p = 0.044). The AT patients displayed a higher percentage of ACS diagnosis (p < 0.001) and received chronic therapy with ACE (angiotensin-converting enzyme) inhibitors (p = 0.001), beta blockers (p = 0.001) and statins (p = 0.013).The AC patients displayed higher platelet reactivity at COL (collagen) test, ASPI test and ADP (adenosine diphosphate) test (p = 0.03, 0.001 and <0.001, respectively) and a higher percentage of HRPR (high residual platelet reactivity) in the ADP test (p = 0.001).No difference was found in the baseline uric acid and creatinine levels between AC and AT patients. At 30–90 days, a significant absolute and percentage increase in the SUA levels was found in AT as compared to AC patients (0.204 mg/dl vs. −0.165 mg/dl, p = 0.034; 6.26% vs. −0.005%, p = 0.018, respectively). Results were not influenced by variations in renal function. At multivariate analysis, in fact, ticagrelor therapy emerged as an independent predictor of increase in the uric acid levels (odds ratio (OR; 95% confidence interval (CI)) = 2.79 (1.66–4.67), p < 0.001). However, the variation in the SUA levels did not affect platelet reactivity or HRPR in both AC and AT patients. ConclusionAn increase in the SUA levels at 30–90 days was observed in patients receiving chronic DAPT with ticagrelor, but not clopidogrel treatment. However, the changes in the SUA levels do not influence platelet aggregation.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence

Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

BackgroundHerpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association.Methods and FindingsThe self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination.ConclusionsStroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a role of zoster vaccination in these associations. These findings enhance our understanding of the temporality and magnitude of the association between zoster and acute cardiovascular events.

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

PAD in women: the ischemic continuum.

Lower extremity peripheral arterial disease (PAD) is part of the ischemic continuum of atherosclerotic vascular disease and is associated with an increased risk of myocardial infarction, stroke, and cardiovascular death. Compared to men, women with PAD are more likely to have asymptomatic disease or atypical symptoms. PAD in women is associated with decreased exercise capacity, reduced quality of life, increased risk of depression, as well as a greater risk of acute cardiovascular events and cardiovascular mortality than male counterparts. Ensuring an appropriate diagnosis of women with PAD offers an opportunity to begin risk factor modification therapy, improve walking capacity and make atimely referral for revascularization if needed. It is critical to highlight the sex-based disparities in lower extremity PAD so that we may work to improve outcomes for women with PAD.

Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity

The risk of acute cardiovascular events is highest during morning hours, and platelet activity peaks during morning hours. The effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity is not known. It was our objective to evaluate the effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity. A randomised open-label cross-over trial in healthy subjects (n=14) was conducted. Participants used acetylsalicylic acid (80 mg) on awakening or at bedtime for two periods of two weeks, separated by a four-week wash-out period. At the end of both periods blood was drawn every 3 hours to measure COX-1-dependent (VerifyNow- Aspirin; Serum Thromboxane B2 [STxB2]) and COX-1-independent (flow cytometry surface CD62p expression; microaggregation) platelet activity. VerifyNow platelet reactivity over the whole day was similar with intake on awakening and at bedtime (mean difference: –9 [95 % confidence interval (CI) –21 to 4]). However, the morning increase in COX-1-dependent platelet activity was reduced by intake of aspirin at bedtime compared with on awakening (mean difference VerifyNow: –23 Aspirin Reaction Units [CI –50 to 4]; STxB2: –1.7 ng/ml [CI –2.7 to –0.8]). COX-1-independent assays were not affected by aspirin intake or its timing. Low-dose aspirin taken at bedtime compared with intake on awakening reduces COX-1-dependent platelet reactivity during morning hours in healthy subjects. Future clinical trials are required to investigate whether simply switching to aspirin intake at bedtime reduces the risk of cardiovascular events during the high risk morning hours.

A score to quantify coronary plaque vulnerability in high-risk patients with type 2 diabetes: an optical coherence tomography study.

BackgroundPatients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes.MethodsOCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology.ResultsMultivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098).Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96).ConclusionThis is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.

Methylmercury-Induced Inhibition of Paraoxonase-1 (PON1)—Implications for Cardiovascular Risk

Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 μg/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.

Comprehensive plaque assessment by coronary CT angiography.

Most acute coronary syndromes are caused by sudden luminal thrombosis due to atherosclerotic plaque rupture or erosion. Preventing such an event seems to be the only effective strategy to reduce mortality and morbidity of coronary heart disease. Coronary lesions prone to rupture have a distinct morphology compared with stable plaques, and provide a unique opportunity for noninvasive imaging to identify vulnerable plaques before they lead to clinical events. The submillimeter spatial resolution and excellent image quality of modern computed tomography (CT) scanners allow coronary atherosclerotic lesions to be detected, characterized, and quantified. Large plaque volume, low CT attenuation, napkin-ring sign, positive remodelling, and spotty calcification are all associated with a high risk of acute cardiovascular events in patients. Computation fluid dynamics allow the calculation of lesion-specific endothelial shear stress and fractional flow reserve, which add functional information to plaque assessment using CT. The combination of morphologic and functional characteristics of coronary plaques might enable noninvasive detection of vulnerable plaques in the future.

Increased Risk of Acute Cardiovascular Events After Partner Bereavement

IMPORTANCE The period immediately after bereavement has been reported as a time of increased risk of cardiovascular events. However, this risk has not been well quantified, and few large population studies have examined partner bereavement. OBJECTIVE To compare the rate of cardiovascular events between older individuals whose partner dies with those of a matched control group of individuals whose partner was still alive on the same day. DESIGN, SETTING, AND PARTICIPANTS Matched cohort study using a UK primary care database containing availale data of 401 general practices from February 2005 through September 2012. In all, 30 447 individuals aged 60 to 89 years at study initiation who experienced partner bereavement during follow-up were matched by age, sex, and general practice with the nonbereaved control group (n = 83 588) at the time of bereavement. EXPOSURES Partner bereavement. MAIN OUTCOMES AND MEASURES The primary outcome was occurrence of a fatal or nonfatal myocardial infarction (MI) or stroke within 30 days of bereavement. Secondary outcomes were non-MI acute coronary syndrome and pulmonary embolism. All outcomes were compared between the groups during prespecified periods after bereavement (30, 90, and 365 days). Incidence rate ratios (IRRs) from a conditional Poisson model were adjusted for age, smoking status, deprivation, and history of cardiovascular disease. RESULTS Within 30 days of their partner's death, 50 of the bereaved group (0.16%) experienced an MI or a stroke compared with 67 of the matched nonbereaved controls (0.08%) during the same period (IRR, 2.20 [95% CI, 1.52-3.15]). The increased risk was seen in bereaved men and women and attenuated after 30 days. For individual outcomes, the increased risk was found separately for MI (IRR, 2.14 [95% CI, 1.20-3.81]) and stroke (2.40 [1.22-4.71]). Associations with rarer events were also seen after bereavement, including elevated risk of non-MI acute coronary syndrome (IRR, 2.20 [95% CI, 1.12-4.29]) and pulmonary embolism (2.37 [1.18-4.75]) in the first 90 days. CONCLUSIONS AND RELEVANCE This study provides further evidence that the death of a partner is associated with a range of major cardiovascular events in the immediate weeks and months after bereavement. Understanding psychosocial factors associated with acute cardiovascular events may provide opportunities for prevention and improved clinical care.

Atrial natriuretic peptide gene variants and circulating levels: implications in cardiovascular diseases

ANP (atrial natriuretic peptide), discovered 30 years ago in rat cardiac atria, has been extensively investigated with regard to physiology, pathophysiology, cardiovascular disease therapeutics and molecular genetic aspects. Besides its diuretic, natriuretic and vasorelaxant effects, novel properties of this hormone have been described. Thus anti-hypertrophic, anti-fibrotic, anti-proliferative and anti-inflammatory actions suggest that ANP contributes not only to haemodynamic homoeostasis and adjustments, but has also a role in cardiovascular remodelling. Circulating ANP levels represent a valuable biomarker in cardiovascular diseases. ANP structure is highly conserved among species, indicating a key role in cardiovascular health. Thus an abnormal ANP structure may contribute to an increased risk of disease due to altered functions at either the vascular or cardiac level. Among others, the 2238T>C exon 3 variant has been associated with endothelial cell damage and dysfunction and with an increased risk of acute cardiovascular events, a frameshift mutation within exon 3 has been related to increased risk of atrial fibrillation, and ANP gene variants have been linked to increased risk of hypertension in different ethnic groups. On the other hand, the rs5068 variant, falling within the 3' UTR and associated with higher circulating ANP levels, has been shown to have a beneficial cardioprotective and metabolic effect. Dissecting out the disease mechanisms dependent on specific ANP molecular variants may reveal information useful in the clinical setting for diagnostic, prognostic and therapeutic purposes. Furthermore, insights from molecular genetic analysis of ANP may well integrate advancing knowledge on the role of ANP as a significant biomarker in patients affected by cardiovascular diseases.

Screen or not to screen for peripheral arterial disease: guidance from a decision model

BackgroundAsymptomatic Peripheral Arterial Disease (PAD) is associated with greater risk of acute cardiovascular events. This study aims to determine the cost-effectiveness of one time only PAD screening using Ankle Brachial Index (ABI) test and subsequent anti platelet preventive treatment (low dose aspirin or clopidogrel) in individuals at high risk for acute cardiovascular events compared to no screening and no treatment using decision analytic modelling.MethodsA probabilistic Markov model was developed to evaluate the life time cost-effectiveness of the strategy of selective PAD screening and consequent preventive treatment compared to no screening and no preventive treatment. The analysis was conducted from the Dutch societal perspective and to address decision uncertainty, probabilistic sensitivity analysis was performed. Results were based on average values of 1000 Monte Carlo simulations and using discount rates of 1.5% and 4% for effects and costs respectively. One way sensitivity analyses were performed to identify the two most influential model parameters affecting model outputs. Then, a two way sensitivity analysis was conducted for combinations of values tested for these two most influential parameters.ResultsFor the PAD screening strategy, life years and quality adjusted life years gained were 21.79 and 15.66 respectively at a lifetime cost of 26,548 Euros. Compared to no screening and treatment (20.69 life years, 15.58 Quality Adjusted Life Years, 28,052 Euros), these results indicate that PAD screening and treatment is a dominant strategy. The cost effectiveness acceptability curves show 88% probability of PAD screening being cost effective at the Willingness To Pay (WTP) threshold of 40000 Euros. In a scenario analysis using clopidogrel as an alternative anti-platelet drug, PAD screening strategy remained dominant.ConclusionThis decision analysis suggests that targeted ABI screening and consequent secondary prevention of cardiovascular events using low dose aspirin or clopidogrel in the identified patients is a cost-effective strategy. Implementation of targeted PAD screening and subsequent treatment in primary care practices and in public health programs is likely to improve the societal health and to save health care costs by reducing catastrophic cardiovascular events.

Primary care of hypertensive patients and the risk of acute cardiovascular events

Purpose: Hypertension is one of the most important risk factors for acute cardiovascular events such as myocardial infarction and stroke. It is unknown which aspects are most important in determining which hypertensive patients have more risk to get an acute myocardial infarction or stroke and get hospitalised for this event. The objective of this study was to establish which factors play a role in determining the risk of an acute cardiovascular event in hypertensive patients. We specifically assessed the difference in use of general practitioner (GP) care, medication and clinical and demographic parameters by comparing two groups of hypertensive patients: those who were hospitalised with an acute cardiovascular event and those who did not experience any acute cardiovascular event. Methods: We linked Dutch Register of General Practitioners (DRGP) and Hospital Discharge Register using personal identification number. From DRGP we identified patients that were diagnosed with hypertension (ICPC code K85, K86 and K87) in 2009 or before. Further we identified which of those patients were hospitalised for myocardial infarction (ICD-9-CM 410) or stroke (ICD-9-CM 430-436) in 2010. Using multilevel logistic regression we identified the risk factors for these hypertensive patients to be hospitalised with an acute myocardial infarction (AMI) or stroke. Findings: In total 34328 hypertensive patients were identified in DRGP. Of those patients 448 were hospitalised with AMI or stroke in 2010. The risk of hospitalisation for AMI or stroke significantly increased with age and with increasing number of cardiovascular diseases (other than hypertension). The risk of hospitalisation for women was lower than that for men. Patients hospitalised for an acute cardiovascular event had more GP contacts of all types (mean = 9,7 contacts for patients hospitalised with an acute event versus 7.9 contacts for patients without acute events). Patients hospitalised with an acute event had also significantly more drugs prescribed, European Forum for Primary Care Conference, Istanbul, September 9-10, 2013. 2 International Journal of Integrated Care – Volume 13, 06 November – URN:NBN:NL:UI:10-1-114900–http://www.ijic.org/ except lipid modifying agents that were equally often prescribed in both groups with and without acute cardiovascular events. Both mean systolic and mean diastolic blood pressure was significantly elevated in patients that were hospitalised with AMI or stroke. Patients hospitalised for an acute event had about 4 times higher risk to have a frequent number (13+) of GP contacts per year. This risk was partly explained by the number of other chronic and other cardiovascular diseases that these patients had. Patients with hypertension that were hospitalised for an acute event had significantly more frequent contacts with their GP already 11 months before hospitalisation compared to hypertensive patients that did not experience an acute event. Discussion: Older male patients and with multiple cardiovascular conditions are at higher risk to be hospitalised for an acute myocardial infarction or stroke. These patients have significantly more contacts with their GP long before hospitalisation. Despite these more frequent contacts and higher number of prescriptions the blood pressure of those patients is less well controlled. The results of this study can help primary care providers better identify patients with hypertensions that are at higher risk for getting an acute cardiovascular event.

Is the Future of Statins Aligned with New Novel Lipid Modulation Therapies?

Dyslipidemia is an established risk factor for the development of atherosclerotic cardiovascular disease. Statin therapy has been proven in a number of clinical trials to lower the risk of acute cardiovascular events and is the mainstay of cholesterol treatment. Despite current optimal treatment for dyslipidemia, many patients fail to reach adequate cholesterol treatment goals and remain at a significantly increased risk of cardiovascular events. Given this residual risk, there is a critical need for additional lipid therapies that could augment the ability of statins to lower the burden of atherogenic lipoproteins and, in some cases, raise levels of high-density lipoproteins. A number of novel lipid-altering therapies have been developed and are currently in clinical trials. In this review, we discuss these promising therapies, which include PCSK9 inhibitors, apolipoprotein B antisense oligonucleotides, microsomal transfer protein inhibitors, thyroid mimetics, and cholesteryl ester transfer protein inhibitors. Although statin therapy is the current recommended primary treatment for dyslipidemia, emerging novel agents may become adjuvant therapies in the treatment of atherosclerotic heart disease.

Role of Mitogen-Activated Protein Kinase Pathways in Multifactorial Adverse Cardiac Remodeling Associated with Metabolic Syndrome

Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia), soluble inflammatory molecules (such as cytokines and chemokines), as well as hormones (such as insulin), characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis) are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs) were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.

Does cholesterol drive atherosclerosis?

O of the most enduring views held by mainstream medicine is the close association between circulating cholesterol and cardiovascular disease and in particular coronary heart disease. Except under rare circumstances, a prerequisite precursor to acute coronary or cardiovascular events of an ischemic nature is atherosclerosis, which is known to start in some individuals at an early age and the prevalence is strongly age dependent. It is widely believed that cholesterol drives atherosclerosis, a notion that can be found in the introductions of hundreds of papers. The advent of non-invasive coronary artery imaging techniques such as electron beam computed tomography and coronary computed tomographic angiography have allowed medical scientists to inadvertently test this hypothesis by direct observation of the prevalence and progression of calcified, mixed and non-calcified coronary plaque. The results of a large number of studies involving a broad spectrum of age, ethnic background and both genders fail to support this hypothesis and in fact find a total lack of correlation between circulating total or LDL cholesterol and coronary plaque burden and progression in individuals with subclinical atherosclerosis, including type 2 diabetics who have well documented elevated risk of acute cardiovascular events. Furthermore, a number of studies have consistently found that lipid lowering, especially with the statin class of drug, fails to impact either the prevalence or progression of subclinical coronary atherosclerosis in either non-diabetics or diabetics. This apparent falsification of the hypothesis that cholesterol drives coronary atherosclerosis continues to be ignored. Furthermore, in true primary prevention trials using statin therapy to prevent acute coronary events in both non-diabetic and diabetic individuals, almost all generate absolute risk reductions that are very small, some would say not clinically significant, and there is no impact on mortality. The belief that this approach represents significant preventive therapy, especially for those who are asymptomatic but judged of high risk, including diabetics, is based on relative risk reductions which have the well recognized and intrinsic potential for exaggerating benefit and misleading clinical practice. Large numbers needed to treat to prevent one acute event suggests the need for a new paradigm.

Sympathetic cardiac modulation and vascular worsening in arteritis: A case report

Increases in sympathetic modulation have been associated with increased risk of acute cardiovascular events in some populations. However, whether altered cardiac autonomic modulation is related to peripheral vascular worsening has not yet been described. In this study, we assessed cardiac autonomic modulation by heart rate variability in two patients with arteritis who were followed up for 5 months. Only the subject who presented high cardiac sympathetic modulation had acute vascular worsening. This case report suggests that cardiac autonomic modulation may be related to vascular worsening in patients with arteritis.

Modulation of H2S Metabolism by Statins: A New Aspect of Cardiovascular Pharmacology

Statins (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors) are commonly used in the treatment of cardiovascular diseases. Statins reduce plasma low-density lipoproteins, inhibit inflammatory reaction, improve endothelial function, ameliorate oxidative stress, and reduce platelet activity. Consequently, statins markedly decrease the risk of acute cardiovascular events. H(2)S is synthesized in all layers of the vascular wall, including the endothelium, smooth muscle cells, and perivascular adipose tissue (PVAT). Recent studies demonstrate that PVAT-derived H(2)S decreases vascular tone by activating K(ATP) and/or KCNQ potassium channels in smooth muscle cells. Lipophilic atorvastatin, but not hydrophilic pravastatin, increases net H(2)S production in PVAT by inhibiting its mitochondrial oxidation, and augments the anticontractile effect of PVAT. Inhibition of H(2)S metabolism results from atorvastatin-induced decrease in coenzyme Q, which is a cofactor of H(2)S oxidation by sulfide:quinone oxidoreductase. In contrast to H(2)S, statins do not impair mitochondrial oxidation of organic substrates. Taking into account antiatherosclerotic and anti-inflammatory effect of H(2)S, the gas may mediate some of the beneficial effects of statins on the cardiovascular system. In addition, specific statins differ in their ability to enhance H(2)S signaling. Since both statins and H(2)S reduce ischemia-reperfusion injury, the possible effect of statins on H(2)S oxidation in other tissues such as the heart and the kidney needs to be examined. Inhibition of H(2)S metabolism may be a new therapeutic strategy to improve H(2)S signaling, especially in the mitochondrial compartment.

Correlation between Inflammation and Fibrinolysis Impairment on Central Obesity: A Study for hsCRP, PAI-1, PAP and TAFI

BACKGROUND: Inflammation in the vascular wall plays an important role in the pathogenesis of atherosclerosis. Current studies have shown that increase of systemic inflammatory marker like the acute phase component C-reactive protein (CRP) are associated with an unfavorable progression of disease and an increased risk for acute cardiovascular events. Recently, a close association of Metabolic Syndrome (MetS) with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MetS. High PAI-1 concentrations may be associated with thrombus formation, also causing cardiovascular events. Therefore, we investigated the association between markers for chronic inflammation (CRP) and the markers of fibrinolytic impairment (PAI-1, PAP, TAFI) in subjects with central obesity.METHODS: This was a cross-sectional study in 80 male Indonesian subjects, aged 30-60 years old with central obesity, conducted from January to March 2008 in Bandung.RESULTS: The study results showed that there was a difference of PAI-1 levels between MetS and Non-MetS group. There were significant correlations between hsCRP and PAI-1 (r=0.252, p=0.024 ), hsCRP and PAP (r=0.253, p=0.024), and also between PAI-1 and PAP (r=-0.239, p=0.033 ) respectively. But, no correlation found between hsCRP and TAFI.CONCLUSIONS: There was correlation between inflammation and fibrinolysis impairment on central obesity. Concentrations oh hsCRP, PAI-1 and TAFI were significantly higher in MetS.KEYWORDS: inflammation, fibrinolysis impairment, hsCRP, PAI-1, PAP, TAFI