Cardiovascular Event Odds Ratio Research Articles

Sjögren syndrome is a hidden contributor of macrovascular and microvascular complications in patients with type 2 diabetes.

To investigate cardiovascular risk among diabetic patients with Sjögren syndrome. This study was a nationwide population-based case-control study from 1997 to 2013, in which the association between autoimmune diseases and diabetes was investigated. The study population consisted of individuals with newly diagnosed type 2 diabetes with macrovascular or microvascular complications with at least two outpatient visits or one hospitalization as the outcome variables, and the exposure variables included traditional risk factors, medications, and autoimmune diseases. The odds ratio of cardiovascular events among each prevalent autoimmune disease and hydroxychloroquine's effect on cardiovascular risk were analyzed. The study included a total of 7026 individuals with diabetes with microvascular and macrovascular complications and the same number of patients in the control group. Sjögren syndrome was significantly higher in the diabetes complication group than in the non-complication group (0.8% vs 0.5%, P=0.036). By using multivariate analysis, we found hypertension, hyperlipidemia, and Sjögren syndrome to be three independent risk factors for diabetes vascular complications (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.82-2.10; OR 1.53, 95% CI 1.42-1.64; and OR 1.67, 95% CI 1.06-2.65; respectively, all P < 0.05). Treatment with traditional statins and aspirin might be able to overcome the increased risk of developing cardiovascular events while comparing between diabetes patients with and without Sjögren syndrome. Sjögren syndrome is an unrecognized independent risk factor for cardiovascular events among diabetes patients, which indicates that patients with diabetes combined with Sjögren syndrome require closer follow up regarding cardiovascular complications in clinical settings. Treatment with hydroxychloroquine might not be enough to lower the cardiovascular risk significantly in diabetes patients with Sjögren syndrome.

Exploring pharmacogenetic difference using adverse event database: an example of clopidogrel and cardiovascular events.

Background: Poor clopidogrel metabolizers, carrying a cytochrome P450 2C19 loss-of-function allele, are more frequent among East Asians than Caucasians/White. Materials & methods: The Korea adverse eventreporting systemdatabase and a case/noncase study design were used to examine the disproportionality of cardiovascular events following clopidogrel use. The USFDA's adverse event reporting systemdatabase was also analyzed for comparison. Results: In the Korea adverse eventreporting system data, the clopidogrel reporting odds ratio for cardiovascular events was 7.34, more than double that of ticagrelor. In the FDA's adverse event reporting system data, the clopidogrel reporting odds ratio was 4.69, lower than that of ticagrelor. Adjustment for covariates did not change the trend. Conclusion: Considering the prevalence of poor clopidogrel metabolizers and the reported cardiovascular events among Koreans, rigorous clinical management is required for clopidogrel users.

Mendelian Randomization Study of ACLY and Cardiovascular Disease

BackgroundATP citrate lyase is an enzyme in the cholesterol–biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl–coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear.MethodsWe constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer.ResultsA total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval [CI], 0.78 to 0.87; P=4.0×10−14) for the ACLY score and 0.836 (95% CI, 0.81 to 0.87; P=3.9×10−19) for the HMGCR score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer.ConclusionsGenetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.)

OP.1A.01] MORE CARDIOVASCULAR EVENTS AMONG WOMEN WITH UTERINE FIBROIDS

Objective: We recently showed that women with uterine fibroids have a higher hypertension risk compared to women without fibroids, independent of age, body mass index and ethnicity. Whether this translates into more cardiovascular events is unknown. Therefore, we assessed the risk of cardiovascular events in women with fibroids. Design and method: Data of the multi-ethnic, cross-sectional National Health and Nutrition Examination Surveys (NHANES) 1999–2006 were analyzed including 11,858 women, aged 18–85 years. Presence of uterine fibroids and previous cardiovascular events (i.e. any cardiovascular event, congestive heart failure, coronary heart disease or stroke) were self-reported. Physical examination included assessment for obesity (BMI >=30.0 kg/m2), hypertension (SBP/DBP >=140/90 mmHg, or antihypertensive treatment), diabetes (fasting glucose >6.9 mmol/L, or antidiabetic medication), and hypercholesterolemia (cholesterol >6.1 mmol/L, or receiving cholesterol-lowering medication). The primary outcome was the independent odds ratio of cardiovascular events in women with and without uterine fibroids. Results: We included 700 women with and 11,158 women without self-reported fibroids. Women with fibroids were younger (43.6 (SD 7.4) vs 46.4 (21.4) years, p < 0.001) and more often African (38.0 vs 19.8%, p < 0.001). In the different age groups, the prevalence of obesity, hypertension and cardiovascular disease was significantly higher in women with fibroids (Figure 1).As expected, women with fibroids had more hypertension (adjusted OR 1.49, 95%CI 1.13–1.97) and obesity (adjusted OR 1.49, 95%CI 1.17–1.89). Importantly, women with fibroids had more stroke (OR 2.25, 95%CI 1.10–4.57), and total cardiovascular disease (OR 2.27, 95%CI 1.42–3.62), adjusted for age, BMI, ancestry, use of hormones, educational level, SBP, fasting glucose and cholesterol. Diabetes and hypercholesterolemia did not differ significantly between women with and without fibroids. Conclusions: We found that women with fibroids have more cardiovascular events than women without fibroids. Further research regarding the underlying pathophysiology is needed. In addition, currently uterine fibroids are classified as a benign condition. However, these data indicate that fibroids may be considered as a marker for cardiovascular risk, warranting early screening and monitoring of the cardiovascular risk profile in women with fibroids.

Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes

BackgroundPharmacologic inhibitors of proprotein convertase subtilisin–kexin type 9 (PCSK9) are being evaluated in clinical trials for the treatment of cardiovascular disease. The effect of lowering low-density lipoprotein (LDL) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes is unknown.MethodsWe used genetic scores consisting of independently inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl–coenzyme A reductase (HMGCR; the target of statins) as instruments to randomly assign 112,772 participants from 14 studies, with 14,120 cardiovascular events and 10,635 cases of diabetes, to groups according to the number of LDL cholesterol–lowering alleles that they had inherited. We compared the effects of lower LDL cholesterol levels that were mediated by variants in PCSK9, HMGCR, or both on the risk of cardiovascular events and the risk of diabetes.ResultsVariants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter (0.26 mmol per liter) in the LDL cholesterol level: odds ratio for cardiovascular events, 0.81 (95% confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR. Variants in these two genes were also associated with very similar effects on the risk of diabetes: odds ratio for each 10 mg per deciliter decrease in LDL cholesterol, 1.11 (95% CI, 1.04 to 1.19) for PCSK9 and 1.13 (95% CI, 1.06 to 1.20) for HMGCR. The increased risk of diabetes was limited to persons with impaired fasting glucose levels for both scores and was lower in magnitude than the protective effect against cardiovascular events. When present together, PCSK9 and HMGCR variants had additive effects on the risk of both cardiovascular events and diabetes.ConclusionsIn this study, variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level. The effects of these variants were independent and additive. (Funded by the Medical Research Council and the National Heart, Lung, and Blood Institute.)

An elevated lipoprotein(a) plasma level as a cardiovascular risk factor

IntroductionThe causal association of elevated lipoprotein(a) (Lp(a)) plasma levels with the increased cardiovascular risk is still controversial and presently there are no standard recommendations on managing of hyperLp(a)emia. Our retrospective analysis is aimed to explore the Lp(a) thresholds, the magnitude of various cardiovascular risk factors and their combinations. MethodsThe files of 544 outpatients from our Outpatient Department of Lipid Disorders were divided into quintiles with respect to Lp(a) levels and reviewed regarding age, gender, Body Mass Index, dyslipidemias, arterial hypertension, diabetes mellitus, smoking and incidence of vascular events in coronaries, carotids and lower extremities. Furthermore we built 15 small quantiles to identify the Lp(a) threshold more precisely. ResultsThe incidence odds ratio for cardiovascular events rose from 2.65 in the 2nd quintile with Lp(a) 483–821 mg/L to 6.36 in the 5th quintile (Lp(a) ≥ 1495 mg/L). The relative risk of cardiovascular events was 0.08 in subjects with a Lp(a) level under 232 mg/l and 3.6 at Lp(a) ≥ 315 mg/L. The magnitude of the combination of elevated Lp (a) with arterial hypertension factor exceeded that of gender, age and combination of arterial hypertension with smoking. ConclusionsA Lp(a) plasma level of higher than about 300 mg/L seems to be a threshold for occurring of cardiovascular events. The combination of raised Lp(a) with arterial hypertension was found to be the most important cardiovascular risk factor. Lp(a) levels under 232 mg/L appeared to be a marker for good prognosis.

Prognostic Implication of Interdialytic Fluid Retention during the Beginning Period in Incident Hemodialysis Patients

Patient with end stage renal disease have characteristics in common with heart failure patients, and volume overload in heart failure is associated with poorer outcomes. Fluid removal during the hemodialysis (HD) is the cornerstone of volume management in this population. The objective of this study is to assess the long-term prognostic effect of interdialytic fluid retention (IDFR) and its relationship with cardiovascular (CV) events in incident HD patients who newly started dialysis. IDFR is defined as the difference between the predialysis weight and the weight at the end of the previous dialysis session, and it mainly reflects the consequence of salt and water intake between two consecutive dialysis sessions. We retrospectively reviewed the 172 patients who newly started and maintained HD over 6 months at Gachon University Gil Hospital between 1 January 2003 and 31 December 2008. The average data were collected for 3 months during the beginning period, including total IDFR and IDFR/dry weight (IDFR%), nutritional parameters, blood pressure, and other biochemical parameters. Patients were classified into 3 cohorts according to the tertile of IDFR%; low (T1; ≤ 3.21%), intermediate (T2; 3.21%-4.56%), and high (T3; ≥ 4.56%). The high IDFR% group showed higher prevalence of diabetes and better nutritional status. The adjusted odds ratio for CV events was 1.562 (95% confidence interval, 1.026-2.378) for high IDFR% group, compared with the low IDFR% group. In incident HD patients, greater IDFR% soon after HD initiation showed an independent association with higher risk for CV events.

A1C and Cardiovascular Outcomes in Type 2 Diabetes

OBJECTIVEType 2 diabetes is associated with increased cardiovascular risk. The role of aggressive glycemic control in preventing cardiovascular events is unclear. A nested case-control study design was used to evaluate the association between average A1C and cardiovascular outcomes.RESEARCH DESIGN AND METHODSAdults with type 2 diabetes were identified among members of Kaiser Permanente Southern California. Type 2 diabetes was identified based on ICD-9 diagnosis codes and either A1C >7.5% or prescriptions for hypoglycemic agents. Case subjects were defined based on nonfatal myocardial infarction, nonfatal stroke, or death attributed to cardiovascular events during a 3-year window. Four type 2 diabetes control subjects were matched to each case subject based on age, sex, and index date for the corresponding case. A conditional logistic regression model was used to estimate the odds ratio of cardiovascular events and compare three patient groups based on average A1C measured in the preindex period (≤6, >6–8, >8%).RESULTSA total of 44,628 control subjects were matched to 11,157 case subjects. Patients with an average A1C ≤6% were 20% more likely to experience a cardiovascular event than the group with an average A1C of >6–8% (P < 0.0001). Patients with an average A1C >8% experienced a 16% increase in the likelihood of a cardiovascular event (P < 0.0001). We found evidence of statistical interaction with A1C category and LDL level (P = 0.0002), use of cardiovascular medications (P = 0.02), and use of antipsychotics (P = 0.001).CONCLUSIONSHigh-risk patients with type 2 diabetes who achieved mean A1C levels of ≤6% or failed to decrease their A1C to <8% are at increased risk for cardiovascular events.

Soluble adhesion molecule E-selectin predicts cardiovascular events in Japanese patients with type 2 diabetes mellitus

Soluble adhesion molecule E-selectin (sE-selectin) is a marker of endothelial activation. To investigate whether high serum concentrations of sE-selectin could predict cardiovascular events, we followed 392 Japanese patients with type 2 diabetes mellitus who had no history of cardiovascular disease for a mean period of 6 years. The cardiovascular end points were defined as fatal and nonfatal myocardial infarction, angina pectoris, stroke, and sudden death. During the follow-up period, 51 patients reached end point. Patients who reached end point were significantly older and had longer duration of diabetes, higher systolic blood pressure, higher hemoglobin A1c, higher plasma glucose, higher sE-selectin, and lower high-density lipoprotein cholesterol compared with those free of such events. The mean serum concentration of sE-selectin was higher in patients who reached end point (81.1 ± 32.2 ng/mL) than event-free patients (66.7 ± 33.7 ng/mL, mean ± SD; P < .01). Multiple logistic regression analysis identified age, systolic blood pressure, total cholesterol, sE-selectin, and low high-density lipoprotein cholesterol as independent factors related to cardiovascular events. The odds ratio for cardiovascular events for 1-SD increase in sE-selectin concentration was 1.45 (95% confidence interval, 1.22-1.71). Kaplan-Meier analysis demonstrated a significantly higher cardiovascular event rate in the highest tertile of sE-selectin compared with the lowest or middle tertile of sE-selectin ( P < .01). The results suggest that high serum concentrations of sE-selectin can predict cardiovascular events in Japanese patients with type 2 diabetes mellitus.

Abstract 2398: Polymorphisms of Angiotensin Converting Enzyme and Endothelial Nitric Oxide Synthase Genes Act Synergistically to Increase the Risk of Cardiovascular Events in Patients with Hypertrophic Cardiomyopathy

Background: Patients with hypertrophic cardiomyopathy (HCM) have a small left ventricular cavity size due to hypertrophy. Therefore, reduction of venous return and intravascular volume in patients with HCM leads to low cardiac output and hypotension. We reported that the angiotensin converting enzyme insertion/insertion (ACE I/I) genotype, which leads to inhibitory renin-angiotensin system, is a significant risk factor for cardiovascular events (CE) in patients with HCM. Recently, the endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp), which plays an important role in the modulation of cardiovascular physiology, is reported to be associated with heart diseases. Methods and Results: Genotyping at these loci was performed in 150 patients with HCM. This study design was a nested case-control study. The cardiovascular events were defined as cardiac death and hospitalization for stroke or congestive heart failure. Patients were divided into two groups: group A of 44 patients (29%) with one or more history of the cardiovascular events and group B of 106 patients (71%) without history of the cardiovascular events. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of CE. The odds ratio for cardiovascular events among persons who had ACE I/I genotype as compared with those with the other ACE genotypes was 2.5 (P &lt; 0.01). In a dominant Asp allele model of the eNOS gene polymorphism, there was a significant difference in genotypes between the two groups (p &lt; 0.01). In addition, there was a marked increase in the risk of CE among persons who were homozygous for both genotypes (ACE I/I and eNOS 298Glu/Glu) (odds ratio, 2.7, P &lt; 0.01). Conclusion: The ACE I/I and eNOS 298Glu/Glu act synergistically to increase the risk of CE in patients with HCM. Genotyping at these two loci may be a useful approach for identification of persons with HCM at risk for CE.

The &amp;#x2018;Arimidex&amp;#x2019;, Tamoxifen, Alone or in Combination (ATAC) Trial: A Step Forward in the Treatment of Early Breast Cancer

The ATAC trial is the first study to compare a third-generation aromatase inhibitor (AI), anastrozole, with tamoxifen for the adjuvant treatment of early breast cancer. Analyses at 33 and 47 months of median follow-up showed that anastrozole significantly prolonged disease-free survival (DFS) and time to recurrence (TTR), and reduced the incidence of contralateral breast cancer, compared with tamoxifen. Results of the Completed Treatment Analysis at 68 months of median follow-up confirmed the superiority of anastrozole over tamoxifen. The absolute difference in DFS between anastrozole and tamoxifen continued to increase beyond completion of treatment and early improvements in DFS and TTR have translated into a benefit in time to distant recurrence. Benefits of anastrozole over tamoxifen were maintained without a detrimental impact on quality of life. Mature safety data with extensive patient exposure indicate that overall, anastrozole has a favourable safety profile compared with tamoxifen. Importantly, a decrease in the odds ratio of cardiovascular events was observed with anastrozole compared with tamoxifen. The ATAC trial provides the most mature data of any AI trial and has enabled the evaluation of a full risk:benefit profile of anastrozole.