Clinical Cardiovascular Disease Outcomes Research Articles

Classification, Diagnosis, and Treatment of Obesity-Related Heart Diseases.

Evidence-based medicine shows that obesity is associated with a wide range of cardiovascular (CV) diseases. Obesity can lead to changes in cardiac structure and function, which can lead to obese cardiomyopathy, subclinical cardiac dysfunction, and even heart failure. It also increases the risk of atrial fibrillation and sudden cardiac death. Many invasive and noninvasive diagnostic methods can detect obesity-related heart disease at an early stage, so that appropriate measures can be selected to prevent adverse CV events. However, studies have shown a protective effect of obesity on clinical outcomes of CV disease, a phenomenon that has been termed the obesity paradox. The "obesity paradox" essentially refers to the fact that the classification of obesity defined by body mass index (BMI) does not consider the impact of obesity heterogeneity on CV disease prognosis, but simply puts subjects with different clinical and biochemical characteristics into the same category. In any case, indicators such as waist-to-hip ratio, ectopic body fat qualitative and quantitative, and CV fitness have been shown to be able to distinguish different CV risks in patients with the same BMI, which is convenient for early intervention in an appropriate way. A multidisciplinary approach, including lifestyle modification, evidence-based generic and novel pharmacotherapy, and surgical intervention, can improve CV outcomes in overweight/obese patients.

Exposure to Arsenic and Subclinical Cardiovascular Disease in 9- to 11-Year-Old Children, Syracuse, New York

Studies in adults have demonstrated associations between arsenic exposure and clinical and subclinical cardiovascular disease (CVD). No studies to date have considered potential associations in children. To examine the association between total urinary arsenic levels in children and subclinical indicators of CVD. This cross-sectional study considered 245 children, a subset from the Environmental Exposures and Child Health Outcomes (EECHO) cohort. Children from the Syracuse, New York, metropolitan area were recruited from August 1, 2013, until November 30, 2017, with enrollment throughout the year. Statistical analysis was performed from January 1, 2022, to February 28, 2023. Total urinary arsenic was measured using inductively coupled plasma mass spectrometry. Creatinine concentration was used to adjust for urinary dilution. In addition, potential exposure routes (eg, diet) were measured. Three indicators of subclinical CVD were assessed: carotid-femoral pulse wave velocity, carotid intima media thickness, and echocardiographic measures of cardiac remodeling. The study sample included 245 children aged 9 to 11 years (mean [SD] age, 10.52 [0.93] years; 133 [54.3%] female). The geometric mean of the creatinine-adjusted total arsenic level in the population was 7.76 μg/g creatinine. After adjustment for covariates, elevated total arsenic levels were associated with significantly greater carotid intima media thickness (β = 0.21; 95% CI, 0.08-0.33; P = .001). In addition, echocardiography revealed that elevated total arsenic was significantly higher for children with concentric hypertrophy (indicated by greater left ventricular mass and greater relative wall thickness; geometric mean, 16.77 μg/g creatinine; 95% CI, 9.87-28.79 μg/g) relative to the reference group (geometric mean, 7.39 μg/g creatinine; 95% CI, 6.36-8.58 μg/g). With respect to exposure source, significant geographic clustering of total arsenic was found in 1 urban area of Syracuse, New York. These findings suggest a significant association between arsenic exposure and subclinical CVD in children. Elevated total arsenic levels were found in an area of Syracuse with known elevations of toxic metals from industrial waste, suggesting historical pollution as a possible source. Given the novelty and potential importance of this association, further research is needed to confirm our findings. Any potential effect of urinary arsenic exposure in childhood on actual clinical CVD outcomes in adulthood remains to be determined.

Elevated resting heart rate is associated with increased radiographic severity of knee but not hand joints

Although the resting heart rate (RHR) predicts the clinical outcomes of cardiovascular disease, chronic obstructive lung disease, diabetes mellitus, and the risk of cancer, its role in patients with musculoskeletal diseases, such as osteoarthritis (OA), remains unclear. We explored the association of the RHR with the extents of radiographic changes in the knees and hands of 2369 subjects from the Dong-gu Study. The radiographic hand and knee joint findings were graded semi-quantitatively; we calculated total hand and knee joint scores. Multiple linear regression was performed to examine the associations between the RHR and the radiographic characteristics of these joints. For the knee joints, the RHR was associated positively with the total (p < 0.01), osteophyte (p < 0.01), joint space narrowing (JSN; p < 0.01), and tibial attrition (p = 0.02) scores after adjustment for age, sex, body mass index, smoking status, alcohol consumption, educational and physical activity levels, and comorbidities. For the hand joints, the RHR was associated positively with the JSN (p = 0.01) and subchondral cyst (p < 0.01) scores after such adjustment. The RHR was not associated with the total, osteophyte, sclerosis, erosion, or malalignment score for the hand joints. This study is the first to reveal an association between the RHR and the radiographic severity of knee, but not hand, OA.

Deacetylation-dependent regulation of PARP1 by SIRT2 dictates ubiquitination of PARP1 in oxidative stress-induced vascular injury

Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disease, which suggests that the regulatory mechanism of PARP1 in cardiovascular disease is unclear. Here, we focused on deacetylation regulatory mechanisms of PARP1 and crosstalk of PARP1 post-translational modifications. We uncovered the crucial molecular interactions and protein modifications of deacetylase Sirtuin 2 (SIRT2) and PARP1 in vascular damage. The results showed that SIRT2 was involved in this process and oxidative stress damage factor PARP1 was a novel physiological substrate of SIRT2. SIRT2 interacted with PARP1 at the PARP-A-helical domain and deacetylated the K249 residue of PARP1. Furthermore, SIRT2 promoted ubiquitination of the K249 residue of PARP1 via mobilization of the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which led to proteasome-mediated degradation of PARP1. Knockout of SIRT2 in mice and cells increased PARP1 acetylation and decreased PARP1 ubiquitination, which in turn aggravated oxidative stress-induced vascular injury and remodeling. Conversely, overexpression of SIRT2 in mice and cells decreased PARP1 acetylation, increased PARP1 ubiquitination, and relieved oxidative stress-induced vascular injury and remodeling. Overall, this study revealed a previously unrecognized mechanistic link between SIRT2 and PARP1 in the regulation of oxidative stress-induced vascular injury.

Abstract P450: Serum Arachidonic Acid Levels in Relation With Outcome of Acute Intracerebral Hemorrhage

Introduction: The correlation between serum polyunsaturated fatty acids (PUFAs) such as Eicosapentaenoic Acid (EPA), Docosahexaenoic Acid (DHA), Arachidonic Acid (AA) and Dihomogammalinolenic Acid (DHLA) levels and clinical outcomes of cardiovascular disease are previously reported. The aim was to investigate serum PUFAs including AA levels to clinical outcome in intracerebral hemorrhage (ICH) patients. Method: From Nov 2012 to Nov 2019, ICH patients within 24 hours from the onset were enrolled. All patients underwent radiological investigations and laboratory examinations including measurement of serum PUFAs levels on admission. We divided patients into two groups, favorable outcome group (mRS at 3 months 0-3) and poor outcome group (mRS at 3 months 4-6). We compared baseline variables including serum PUFAs levels between two groups. Result: We enrolled 142patients (87 male, median age 60 years old, median NIHSS score 8). Of them, 113 patients (80%) were favorable outcome group and 29 patients (20%) were poor outcome group. Higher NIHSS score and larger size of hematoma on admission were found in poor outcome group (median NIHSS score 6 of favorable outcome vs. 14 of poor outcome, p&lt;0.001, and median hematoma size, 7.5ml vs. 13.5ml, p=0.048). In serum PUFAs levels, only serum AA levels was significantly lower in poor outcome group (median interval 213μg/ml vs. 179μg/ml, p=0.002) though there were no difference of DHLA, EPA and DHA levels between two groups. In multivariate logistic regression analysis, lower serum AA levels was independently associated with poor outcome (OR 0.987, 95%CI 0.978-0.996, p=0.007, Figure). Conclusion: Serum AA levels may play an important role in predicting the outcome in ICH.

Cardiovascular Risk in Postmenopausal Women with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age. The hormonal alterations of PCOS have been linked with a higher risk of metabolic disturbances in young, reproductively active women. However, it remains to be clarified whether the presence of PCOS increases the risk of cardiovascular disease (CVD) later in life. Aging ameliorates the clinical manifestations of PCOS; hyperandrogenaemia and metabolic abnormalities, however, persist beyond the menopause. On the other hand, aging and menopause increase CVD risk in the general female population. The results of the limited available studies in aging women with a previous diagnosis of PCOS demonstrate early atherosclerosis. However, studies addressing clinical CVD outcomes in women with PCOS report inconsistent findings. A possible explanation for this heterogeneity is the difficulty in diagnosing PCOS after the menopausal transition, due to the absence of validated diagnostic criteria for this population. Larger prospective studies of women diagnosed during their reproductive years will shed more light on the longer-term CVD implications of PCOS.

Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study.

OBJECTIVEThe Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.RESEARCH DESIGN AND METHODSA total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years.RESULTSHigher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors.CONCLUSIONSDuring DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

Progression of subclinical and clinical cardiovascular disease in a UK SLE cohort: the role of classic and SLE-related factors

ObjectivesWe aimed to describe the rate and determinants of carotid plaque progression and the onset of clinical cardiovascular disease (CVD) in a UK SLE cohort.MethodsFemale patients with SLE of white...

Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review

ObjectiveTo investigate the effect of endocrine therapies on a wide range of specific clinical cardiovascular disease outcomes in women with a history of non-metastatic breast cancer.DesignSystematic review and meta-analysis of...

Dietary intakes of flavan-3-ols and cardiovascular health: a field synopsis using evidence mapping of randomized trials and prospective cohort studies

BackgroundThere is considerable interest in the impact of increased flavan-3-ol intake on cardiovascular disease (CVD) and diabetes outcomes. Through evidence mapping, we determined the extent of the evidence base to initiate a future systematic review investigating the impact of flavan-3-ol intake on CVD and diabetes outcomes.MethodsWe developed a research protocol, convened a technical expert panel (TEP) to refine the specific research questions, conducted a systematic search in multiple databases, double-screened abstracts and full-text articles, performed data extractions, and synthesized the data. We focused on randomized controlled trials (RCTs) and prospective cohort studies which assessed intakes of flavan-3-ol from foods, beverages, and supplement/extract sources on biomarkers and clinical outcomes of CVD and diabetes.ResultsOf 257 eligible articles, 223 and 34 publications contributed to 226 RCTs and 39 prospective cohort studies, respectively. In RCTs, the most frequently studied interventions were cocoa-based products (23.2%); berries (16.1%); tea in the form of green tea (13.9%), black tea (7.2%), or unspecified tea (3.6%); and red wine (11.2%). Mean total flavan-3-ol intake was highest in the cocoa-based trials (618.7 mg/day) and lowest in the interventions feeding red wine (123.7 mg/day). The most frequently reported outcomes were intermediate biomarkers including serum lipid levels (63.4%), blood glucose (50.9%), blood pressure (50.8%), flow-mediated dilation (21.9%), and high-sensitivity C-reactive protein (21.9%). The included 34 prospective cohort studies predominantly examined exposures to flavan-3-ols (26%), cocoa-based products (23.2%), berries (16.1%), and green tea (13.9%) and CVD incidence and mortality.ConclusionThrough a systematic, evidence-based approach, evidence mapping on flavan-3-ol intake and CVD outcomes demonstrated sufficient data relating to flavan-3ol intake and biomarkers and clinical outcomes of CVD and diabetes. The current evidence base highlights the distribution of available data which both support the development of a future systematic review and identified the research need for future long-term RCTs.Systematic review registrationAt present, evidence mapping is not eligible for registration on the international prospective register of systematic reviews (i.e., PROSPERO).

Scientific Contributions of Population-Based Studies to Cardiovascular Epidemiology in the GWAS Era.

Longitudinal, well phenotyped, population-based cohort studies offer unique research opportunities in the context of genome-wide association studies (GWAS), including GWAS for new-onset (incident) cardiovascular disease (CVD) events, the assessment of gene x lifestyle interactions, and evaluating the incremental predictive utility of genetic information in apparently healthy individuals. Furthermore, comprehensively phenotyped community-dwelling samples have contributed to GWAS of numerous traits that reflect normal organ function (e.g., cardiac structure and systolic and diastolic function) and for many traits along the CVD continuum (e.g., risk factors, circulating biomarkers, and subclinical disease traits). These GWAS have heretofore identified many genetic loci implicated in normal organ function and different stages of the CVD continuum. Finally, population-based cohort studies have made important contributions to Mendelian Randomization analyses, a statistical approach that uses genetic information to assess observed associations between cardiovascular traits and clinical CVD outcomes for potential causality.

Avocado consumption and risk factors for heart disease: a systematic review and meta-analysis

Nutrients in avocados are associated with cardiovascular benefits. The aim of this study was to determine the effect of avocado intake on cardiovascular disease (CVD) risk with the use of a systematic review and meta-analysis. MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched from 1946 through September 2017 for publications on avocado intake and CVD risk. All designs except for cross-sectional studies that evaluated avocado intake were included. Two investigators independently screened citations and extracted data. Random-effects models meta-analysis was used when ≥3 studies reported the same outcome. Of 18 eligible studies (481 subjects), 7 studies compared avocado intake with no intake, 3 studies compared avocado plus monounsaturated fat intake with a control, and 8 studies reported data for qualitative synthesis. In 7 studies, avocado intake significantly increased HDL cholesterol (summary net change: 2.84 mg/dL; 95% CI: 0.18, 5.49 mg/dL), with significant heterogeneity. This remained consistent in sensitivity and subgroup analyses. There was no significant difference between avocado intake and the control for the outcomes of serum total cholesterol (TC), LDL cholesterol, triglycerides (TGs), ratios of TC to HDL cholesterol and LDL cholesterol to HDL cholesterol, and body weight. In qualitative synthesis, there was no significant difference between groups for blood glucose (2 studies), homeostasis model assessment (1 of 2 studies), oxidized LDL (2 studies), high-sensitivity C-reactive protein (2 studies), or apolipoprotein B (2 studies) or, in 1 study each, for body mass index, systolic and diastolic blood pressure, arterial compliance, fibrinogen, interleukin 6, tumor necrosis factor α, and serum nitric oxide. No studies reported incident clinical outcomes of CVD, including myocardial infarction, stroke, and other clinical endpoints. Avocado intake resulted in no difference in serum TC, LDL-cholesterol, and TG concentrations, but it did increase serum HDL-cholesterol concentrations, with significant heterogeneity. The association between avocado intake and CVD risk should be confirmed by well-conducted prospective observational studies or long-term trials.

Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review.

Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.

Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review.

The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes. Evaluate the effect of n-3 FA on clinical and selected intermediate CV outcomes and the association of n-3 FA intake and biomarkers with CV outcomes. The n-3 FA under review include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), stearidonic acid (SDA), and alphalinolenic acid (ALA). MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CAB Abstracts from 2000 or 2002 to June 8, 2015, and eligible studies from the original reports and relevant existing systematic reviews. We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids). From 11,440 citations (from electronic literature searches and existing systematic reviews), 829 abstracts met basic eligibility criteria; 61 RCTs and 37 longitudinal observational studies (in 147 articles) were included. Most RCTs and observational studies had few risk-of-bias concerns. The 61 RCTs mostly compared marine oil supplements with placebo on CVD outcomes in populations at risk for CVD or with CVD, while the 37 observational studies mostly examined associations between various individual n-3 FA and long-term CVD events in generally healthy populations. Compared with the prior report on n-3 FA and CVD, there is more robust RCT evidence on ALA and on clinical CV outcomes; also, by design there are newly added data on associations between n-3 FA biomarkers and CV outcomes. However, conclusions regarding the effect of n-3 FA intake on CV outcomes or associations with outcomes remain substantially unchanged. Marine oils statistically significantly raise HDL-c and LDL-c by similar amounts (≤2 mg/dL), while lowering Tg in a dose-dependent manner, particularly in individuals with elevated Tg; they have no significant effect on BP. ALA has no significant effect on intermediate outcomes. Limited data were available from RCTs on the effect of n-3 FA on clinical CVD outcomes. Observational studies suggest that higher marine oil intake (including from dietary fish) is associated with lower risk of several CVD outcomes. No clear differences in effects or associations were evident based on population, demographic features, or cointerventions. Future RCTs would be needed to establish adequate evidence of the effect of n-3 FA on CVD outcomes or to clarify differential effects in different groups of people. However, future trials are unlikely to alter conclusions about the effects of n-3 FA supplementation on intermediate cardiovascular outcomes (BP, LDL-c, HDL-c, or Tg).

Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis.

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta-analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta-analysis, with sub-group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (-2.68 mmHg, 95% CI -3.37, -2.11), diastolic blood pressure (-1.34 mmHg, 95% CI -1.71, -0.97), low-density lipoprotein cholesterol (-0.20 mmol L(-1) , 95% CI -0.29, -0.10), triglycerides (-0.13 mmol L(-1) , 95% CI -0.22, -0.03), fasting plasma glucose (-0.32 mmol L(-1) , 95% CI -0.43, -0.22) and haemoglobin A1c(-0.40%, 95% CI -0.52, -0.28) over 6-12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub-group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity.

Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids.

Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015. In addition to robust LDL-C lowering (nearly 50-65% from baseline), they improve other lipid parameters as well. Adverse events associated with these medications are minimal. Importantly, they improve clinical cardiovascular disease outcomes, although long-term study results are awaited. Cost may be an important limiting factor in their use and we propose two possible solutions which can potentially curtail cost.

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study. Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC). 3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022). There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.

Influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated with clopidogrel

CYP2C19 genetic polymorphisms influence clopidogrel response and clinical outcomes of cardiovascular disease. However, data on their relationship in stroke patients are scarce. We aimed to investigate the influence of CYP2C19 polymorphisms on platelet reactivity and clinical outcomes in ischemic stroke patients treated with clopidogrel. A total of 211 patients were enrolled. All patients were given clopidogrel treatment and underwent CYP2C19 genotyping and platelet function testing by flow cytometry including adenosine diphosphate-induced platelet aggregation (ADP-PAg) and platelet activation markers (PAC-1, CD62P and CD63). The modified Rankin Scale (mRS) was used and ischemic events were evaluated. A total of 129 (61.1%) of the 211 enrolled patients were carriers of CYP2C19 loss-of-function (LOF) alleles (⁎2, ⁎3). After clopidogrel therapy for 7 days, the levels of ADP-PAg, PAC-1, CD62P and CD63 were higher in carriers than noncarriers. CYP2C19 carriage was associated with more frequent high residual platelet reactivity. CYP2C19 polymorphisms alone could explain 12.9%, 4.3%, 8.9% and 5.5% of the inter-individual variability of ADP-PAg, PAC-1, CD62P and CD63 after clopidogrel treatment, respectively. At 6-month follow-up, 38 (19%) patients were scored poor prognosis and 15 (7.6%) ischemic events were observed. Carriers had poorer prognosis than noncarriers (P=0.025). No significant association of CYP2C19 carriage with ischemic events was found. Multiple regression analysis showed that CYP2C19 carriage was an independent predictor of poor prognosis (odds ratio, 3.01; 95% confidence interval, 1.23–7.38; P=0.016). In conclusion, carriage of the CYP2C19 LOF allele has significant influence on clopidogrel response and prognosis in patients with ischemic stroke.

Abstract 433: Role And Importance Of Antecedent Blood Pressure In Predicting Outcomes In Cardiovascular Disease

Background: Blood pressure levels have been shown to be predictive of subclinical and clinical cardiovascular disease (CVD).There is little published information concerning the influence of antecedent blood pressure levels and HTN on CVD risk. Our hypothesis was that adding antecedent HTN to predictive model will increase model quality and consequently our ability to tailor treatment to patients needs. Methods: We used data for 3344 participants from Framingham Heart Study Offspring who attended exam 3 and were followed up to 20 years for a first CVD event and analyzed prediction improvement reflected in changes in C-index, Net Reclassification Index (NRI) and the Integrated Discrimination Increment (IDI) values. Being exposed to serious critique in last 3 years, caused by improper overuse, this technique remains scientifically valid. Results: Antecedent BP is important independent predictor of CVD outcomes, surprisingly replacing current BP and BP treatment. Change in C-statistic was not statistically significant (p=0.19), which can be expected in saturated models with high c-index values. Both the IDI test (p=0.004) and the NRI test (p=0.046) indicate a significant improvement in the number of properly reclassified patients. Discussion and conclusion: Using information from personal medical history to properly diagnose patients is well established, while using that information in epidemiology was neglected, almost forbidden. Our hypothesis that adding antecedent BP to predictive model will help to properly classify patients was confirmed, so in reverse of roles, epidemiology result confirms practice, underlying need to use information from personal medical history.

Left Ventricular Geometry and All-cause Mortality in Advanced Age

Abnormalities of cardiac structure and function are common in a wide range of populations including those with and without established clinical cardiovascular disease (CVD). This study reports the prevalence of left ventricular hypertrophy (LVH), the four patterns of LV geometry and establishes clinical characteristics and five-year outcomes of each group in people of advanced age. A study conducted in general practices and Māori Health Services in three New Zealand North Island locations. One hundred participants had a full clinical echocardiogram performed and analysed in 2008 by one experienced cardiologist blinded to the participant's clinical history. Two-thirds of the participants had CVD. Thirty-two participants had echocardiographic LVH. Those with LVH had higher left atrial area [median (IQR) 26.4cm(2) (10.9) vs. 22.0cm(2) (7.0), p<0.01] and E/e' [median (IQR) 13 (6.8) vs.10.8 (4.1), p=0.01] than those without LVH. Of those with LVH, 10 demonstrated concentric hypertrophy (CH) and 22 eccentric hypertrophy (EH); 12 concentric remodelling (CR) and 40 normal geometry (NG). Both CR and EH were independently associated with higher risk of all-cause mortality (p<0.01) and hospital admissions (p<0.05) than those with NG. Those with EH also had a higher risk of CVD events (p=0.029). Despite a high prevalence of CVD and hypertension in this sample, half had normal LV geometry. Concentric remodelling and eccentric hypertrophy were associated with higher mortality and adverse CVD outcomes in people of advanced age.