Cardiovascular Disease In High-risk Patients Research Articles

Rapid reduction in uric acid by a urate-lowering agent is associated with recurrent cardiovascular events

ObjectivesResults from a recent study showed that the risk of cardiovascular and all-cause mortality was higher in patients who received febuxostat, a potent urate-lowering agent, than that in patients who received allopurinol. Therefore, we hypothesized that an abrupt change in serum urate levels caused by urate-lowering agents would influence the risk of cardiovascular events. MethodsWe included patients with a history of cardiovascular disease (CVD) who received allopurinol or febuxostat. Cardiovascular events were defined as follows: nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, and cardiovascular death. The change in serum urate levels was determined by the difference or reduction rate in urate within 6 months after exposure to allopurinol or febuxostat. The factors associated with cardiovascular events were evaluated by Cox regression analysis. ResultsIn total, 207 patients with CVD who were exposed to allopurinol or febuxostat were included. Cardiovascular events occurred in 38 patients (18.4%). In univariate analysis, age, diabetes mellitus, baseline urate levels, difference in mean urate levels between baseline and post-exposure (Δuratemean), and reduction rate in urate to the lowest post-exposure levels (Δuratelowest/day) were associated with cardiovascular events. Further, results from the multivariate analysis revealed that age [hazard ratio (HR) 1.036, 95% confidence interval (CI), 1.001–1.072, p = 0.042], Δuratemean (HR 1.188, CI, 1.033–1.366, p = 0.015), and Δuratelowest/day (HR 6.963, CI, 2.215–21.886, p = 0.001) were associated with cardiovascular events. ConclusionRapid reduction in serum urate levels was associated with a higher risk of cardiovascular events. Thus, careful attention should be paid to abruptly changing serum urate levels after treating urate-lowering agent in high-risk CVD patients.

Primary Prevention of Cardiovascular Risk in Lithuania-Results from EUROASPIRE V Survey.

Background and Objectives: Cardiovascular disease (CVD) prevention guidelines define targets for lifestyle and risk factors for patients at high risk of developing CVD. We assessed the control of these factors, as well as CVD risk perception in patients enrolled into the primary care arm of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE V) survey in Lithuania. Materials and Methods: Data were collected as the part of the EUROASPIRE V survey, a multicenter, prospective, cross-sectional observational study. Adults without a documented CVD who had been prescribed antihypertensive medicines and/or lipid-lowering medicines and/or treatment for diabetes (diet and/oral antidiabetic medicines and/or insulin) were eligible for the survey. Data were collected through the review of medical records, patients’ interview, physical examination and laboratory tests. Results: A total of 201 patients were enrolled. Very few patients reached targets for low-density lipoprotein cholesterol (LDL-C) (4.5%), waist circumference (17.4%) and body mass index (15.4%). Only 31% of very high CVD risk patients and 52% of high-risk patients used statins. Blood pressure target was achieved by 115 (57.2%) patients. Only 21.7% of patients at very high actual CVD risk and 27% patients at high risk correctly estimated their risk. Of patients at moderate actual CVD risk, 37.5% patients accurately self-assessed the risk. About 60%–80% of patients reported efforts to reduce the intake of sugar, salt or alcohol; more than 70% of patients were current nonsmokers. Only a third of patients reported weight reduction efforts (33.3%) or regular physical activity (27.4%). Conclusions: The control of cardiovascular risk factors in a selected group of primary prevention patients was unsatisfactory, especially in terms of LDL-C level and body weight parameters. Many patients did not accurately perceive their own risk of developing CVD.

725 Cost Effectiveness of Bempedoic Acid for Those at High Risk Cardiovascular Disease

Bempedoic acid is a novel adenosine triphosphate (ATP) citrate lyase inhibitor. The Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Harmony trial demonstrated that bempedoic acid, in addition to statin therapy, significantly reduced low-density lipoprotein cholesterol (LDL-C) in patients at high risk of cardiovascular disease (CVD). The price at which bempedoic acid would be considered cost-effective to the Australian healthcare system is currently unknown. A Markov model was designed comprising 1000 patients profiled on the CLEAR Harmony cohort, to model their clinical outcomes and costs over a 25-year time horizon. The health states were: ‘Alive with CVD’, ‘Alive with Recurrent CVD’ and ‘Dead’. Patients were at risk of coronary revascularisation, non-fatal myocardial infarction and death from CVD or non-CVD causes in each annual cycle. Costs and utility data were estimated from published sources. Outcomes of interest were the incremental cost-effectiveness ratios (ICERs) based on cost per quality-adjusted life year (QALY) and cost per year of life saved (YoLS). All outcomes were discounted at 5% per year. At AU$584.40 per annum, bempedoic acid in addition to statin therapy, was estimated to save 0.122 (discounted) years of life and 0.103 (discounted) QALYs per person at a net cost of AU$5,159 per person. Overall, this resulted in ICERs of AU$49,980 per QALY gained and $42,433 per YoLS. Bempedoic acid is a promising adjunct therapy for the management of high CVD risk patients and would be considered cost-effective if its annual acquisition cost does not exceed AU$600 per person.

Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease.

Purpose of reviewIn chronic kidney disease (CKD), disturbance of several metabolic regulatory mechanisms cause premature ageing, accelerated cardiovascular disease (CVD), and mortality. Single-target interventions have repeatedly failed to improve the prognosis for CKD patients. Epigenetic interventions have the potential to modulate several pathogenetic processes simultaneously. Alkaline phosphatase (ALP) is a robust predictor of CVD and all-cause mortality and implicated in pathogenic processes associated with CVD in CKD.Recent findingsIn experimental studies, epigenetic modulation of ALP by microRNAs or bromodomain and extraterminal (BET) protein inhibition has shown promising results for the treatment of CVD and other chronic metabolic diseases. The BET inhibitor apabetalone is currently being evaluated for cardiovascular risk reduction in a phase III clinical study in high-risk CVD patients, including patients with CKD (ClinicalTrials.gov Identifier: NCT02586155). Phase II studies demonstrate an ALP-lowering potential of apabetalone, which was associated with improved cardiovascular and renal outcomes.SummaryALP is a predictor of CVD and mortality in CKD. Epigenetic modulation of ALP has the potential to affect several pathogenetic processes in CKD and thereby improve cardiovascular outcome.

Correction of hypertriglyceridemia in order to reduce the residual risk in atherosclerosis-related diseases. Expert Council Opinion

In opinion the Expert council provides management tactics for patients with hypertriglyceridemia (HTG). It is demonstrated that HTG is a common condition in overweight patients and is an important component of residual risk. HTG creates additional conditions for the progression of atherosclerosis, so the level of triglycerides (TG) is recommended to be measured in patients with a high, very high and extremely high risk level. An indication for the appointment of drugs that reduce the concentration of TG is its level of more than 2,3 mmol/L. Statins are the agents of choice to reduce the risk of cardiovascular disease in high-risk patients with hypercholesterolemia and HTG. Fenofibrate is used to correct HTG, and in case of intolerance to it or when the target level of TG is not reached, omega-3 ethers of polyunsaturated fatty acids in a dose of 2-4 g/day are recommended. In patients with HTG with a TG level >5,6 mmol/L, fenofibrate is the agent of choice.

Use of the PCSK9 inhibitor, evolocumab, in patients with heterozygous familial hypercholesterolemia

Evolocumab is a monoclonal immunoglobulin G2 that acts against human proprotein convertase subtilisin/kexin type 9 (PCK9) used against Homozygous familial hypercholesterolemia and Heterozygous familial hypercholesterolemia in high cardiovascular disease risk patients with increased level of triglycerides. Evolocumab is administered subcutaneously 420mg every month and 140 mg twice a week in patients with HeFH as evaluated by RUTHERFORD and RUTHERFORD 2 trials. This paper reviews the six clinical trials of evolocumab that evaluated the efficacy of the drug for heterogenous familial hypercholesterolemia.

Total and Subtypes of Dietary Fat Intake and Its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk.

Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55–75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3–1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia.

Thyroid stimulating hormone suppression time on cardiac function of patients with differentiated thyroid carcinoma

BackgroundThis study was to investigate the influence of thyroid stimulating hormone (TSH) suppression time on the cardiac function of differentiated thyroid carcinoma (DTC) patients.Methods105 DTC patients were divided into strict TSH suppression group (model group, TSH ≤ 0.1 mU/L) and general TSH suppression group (control group, TSH > 0.1 mU/L). According to the suppression time, these two groups were respectively divided into three groups: group within half a year, group between half a year and a year and group more than a year. Gated myocardial perfusion imaging was applied to observe differences of left ventricle (LV) myocardial perfusion, LV diastolic and systolic function and LV systolic synchrony in every group.ResultsThe left ventricular diastolic function, systolic synchrony and myocardial perfusion level of model group decreased with prolonged suppression time. The values of left ventricular EF, PFR and BPM in patients less than half a year were higher than those in 6 months to 1 year for control group.ConclusionThyroid stimulating hormone suppression can influence the cardiac function of patients and with the prolongation of suppression time, regardless of the level of TSH suppression, the possibility of cardiac function depression in patients will increase. TSH may lower the risk of cardiovascular disease in high-risk patients than those in TSH patients with moderate or low risk. The drugs improving cardiac function should be used cooperatively in different suppression period to decrease the occurrence rate of cardiac adverse reactions.

Combination of SGLT-2 Inhibitors and GLP-1 Receptor Agonists: Potential Benefits in Surrogate and Hard Endpoints.

The treatment of type 2 diabetes mellitus (T2DM) is complex; only a few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). SGLT2i, an emerging class of antidiabetic agents with an insulin-independent mechanism of action, are suitable for use in combination with any other class of antidiabetics, including insulin. The use of SGLT2i causes a reduction in Cardiovascular Disease (CVD) morbidity (mainly heart failure-HF) as well as total and CVD mortality. Besides insulin, SGLT2i may also be combined with incretin-based therapies, such as GLP-1 RA. The latter appears to reduce the rate or the progression of both macrovascular (mainly myocardial infarction-MI and stroke) and microvascular complications of DM, having a beneficial effect on all-cause mortality and CVD mortality, as well as CVD events. SGLT2i and GLP-1 RA may have a synergic effect on glucose reduction, weight reduction, renal impairment (both an independent lethal disease and a CVD risk factor) improvement, and cardiac event reduction, because the first reduces HF and related events and the second decreases CVD risk (mainly MI and stroke). Both also reduce total mortality, especially when combined with a statin. The combination of metformin with SGLT2i, GLP-1 RA, and a potent statin, in high CVD risk patients with DM, is expected to substantially reduce CVD mortality and morbidity, improving the quality of life of patients with DM at the same time. Prospective studies are needed to confirm this finding.

Effect of Asian BMI on risk of chronic disease progression: A Singapore perspective

Objectives: High body mass index (BMI) has been associated with increased mortality, healthcare utilization and costs. This study investigates the one-year chronic disease progression and risk of developing diabetes with varying cardiovascular disease (CVD) risks based on the Asian BMI categories. Methods: Patients with BMI information from 2008 to 2014 were included in the analysis ( N=23,508). Patients were stratified into low, moderate, high and very high CVD risk categories. To study disease progression for patients with varying CVD risks, patients were further segmented into seven mutually exclusive disease states based on prevalence of chronic diseases and their complications. The categories were no known chronic disease, at-risk of developing chronic disease, one chronic condition, more than two chronic conditions, chronic conditions with complications, patients with cancer and death. Logistic regression was used to determine the association of CVD risk categories and risk of having diabetes. Results: High CVD risk patients had more chronic diseases in the following year as compared with low CVD risk patients. With reference to low CVD risk patients, patients in the moderate, high and very high risk categories had an odds ratio of 1.78 (95% confidence interval (CI): 1.60 to 1.98), 2.84 (95% CI: 2.51 to 3.21) and 3.99 (95% CI: 3.30 to 4.82) for having diabetes after adjusting for age, gender and ethnicity. Conclusions: Higher BMI is associated with greater chronic disease progression in the following year. Diet control and lifestyle modifications should be encouraged to prevent people from shifting to higher BMI strata as this can be detrimental in the long run.

The association between high-density lipoproteins and estimated glomerular filtration rate in patients without severe kidney disease.

Several studies investigated the association between the estimated glomerular filtration rate (eGFR) and the concentration of high-density lipoproteins (HDL) in patients without severely damaged kidney function. As results of those studies were inconclusive and contradictory, we wanted to investigate this association in multiple cardiovascular disease (CVD) risk patients without severe kidney disease or renal failure. We enrolled a cohort of 187 patients with intermediate and high CVD risk without severe renal disease. We grouped them based on their eGFR into: group 1 (≥ 30 < 60ml/min/1.73m2), group 2 (≥ 60 < 90ml/min/1.73m2) and group 3 (≥ 90ml/min/1.73m2). We analyzed the difference between their HDL levels and assessed the association of HDL and eGFR in three regression models with the following predictors: model 1 (age and gender), model 2 (model 1 plus smoking status, hs-CRP and diabetes mellitus) and model 3 (model 2 plus excessive weight and obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, family history of CVD and medications they used). Patients with the lowest eGFR had the lowest HDL values (P = 0.013). In multiple linear regression, HDL was an independent predictor of eGFR (β = 0.189, P = 0.025) which was also shown in multinomial regression for all three models: model 1 [odds ratio (OR) 0.05; 95% confidence interval (CI) 0.007-0.331; P = 0.002], model 2 (OR 0.052; 95% CI 0.006-0.428; P = 0.006) and model 3 (OR 0.2; 95% CI 0.001-0.309; P = 0.005). Low HDL is an independent predictor of lower eGFR in intermediate and high CVD risk patients without severe kidney disease. In such patients, low HDL could be one of the early indicators of renal failure.

Direct Adherence Measurement Using an Ingestible Sensor Compared With Self-Reporting in High-Risk Cardiovascular Disease Patients Who Knew They Were Being Measured: A Prospective Intervention.

BackgroundUse of appropriate cardioprotective medication is a cornerstone of cardiovascular disease prevention, but less-than-optimal patient adherence is common. Thus, strategies for improving adherence are recommended to adopt a multifaceted approach.ObjectiveThe objective of our study was to test a system comprising a biodegradable, ingestible sensor for direct measurement of medication ingestion in a group of patients at elevated cardiovascular risk attending a cardiac prevention and rehabilitation program.MethodsIn this prospective intervention trial in a single group of 21 patients running from April 2014 to June 2015, we measured adherence by self-report and adherence determined objectively by the system. The sensor emits a signal when it encounters the acidic environment of the stomach, detectable by an externally worn patch and linked software app. Longitudinal adherence data in the form of daily progress charts for sensed dosing events as compared with scheduled dosing are visible to patients on their tablet computer’s medication dosing app, thus providing patients with continuous medication adherence feedback. We sought feedback on patient acceptability by questionnaire assessment. Participants used the system for the 12-week period of their cardiac prevention and rehabilitation program.ResultsOnly 1 patient at initial assessment and 1 patient at end-of-program assessment reported often missing medication. The remaining patients reported never missing medication or had missing data. Only 12 (57%) of patients overall achieved system-determined adherence of 80% or more, and 3 patients had scores below 40%. Participants reported high levels of acceptability.ConclusionsThis integrated system was well tolerated in a group of 21 patients over an appreciable time frame. Its ability to measure adherence reveals the sizeable disconnect between patient self-reported adherence and actual medication taking and has promising potential for clinical use as a tool to encourage better medication-taking behavior due to its ability to provide continuous patient-level feedback.

Abstract P278: Potential Value of Long-term Intensive BP Treatment in 40-year Patients: A Computer Simulation Study

Introduction: Intensive blood pressure (BP) goals are considered for high cardiovascular disease (CVD) risk adults ≥50 years old; the long-term value of intensive BP goals in younger high CVD risk patients has not been studied. Objectives: We used individual patient computer simulations to assess the incremental value of intensive BP goals in high CVD risk patients as young as 40 years. Methods: Six age/sex cohorts of 100,000 individuals were assembled by sampling NHANES surveys 1999-2010. BP and other risk factor trajectories were projected from ages 60 to 69, 50 to 69, and 40 to 69 years based on Framingham Offspring Cohort analyses. One BP treatment scenario simulated treating BP &lt;140/90 mmHg in all patients ≥140/90; a second scenario added to the first a goal &lt;BP 130/90 mmHg in patients with systolic BP ≥130 and 10-year CVD risk ≥10%. Costs included added treatment and side-effect costs and avoided CVD costs. Incremental cost-effectiveness ratios (ICERs) assessed changes in costs and quality-adjusted life years due to adding intensive BP goals in each cohort. Results: Intensive goals were generally cost-effective in high-risk CVD risk patients (Table). Treating 40-year old cohorts was the highest value strategy. This was because of large life-year gains when events are prevented early in life and because hypertensive 40 year-olds “age into” much higher BPs and CVD risk over time. To illustrate the latter, mean untreated systolic BPs at age 60 were 152, 148, and 146 mmHg, and mean 10-year CVD risk scores were 17%, 15% and 13% for 40-, 50- and 60-year-old male cohorts, respectively. Conclusion: Intensive BP goals were projected to be cost-effective over a 30-year time horizon in high-risk hypertensive patients as young as 40 years old.

Evacetrapib: Another CETP Inhibitor for Dyslipidemia With No Clinical Benefit.

Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has been recently studied as a cholesterol modifying agent to reduce cardiovascular risk and mortality in high risk cardiovascular disease patients. Evacetrapib acts to decrease lipid exchange through CETP inhibition. CETP acts to transfer cholesteryl esters from high-density lipoprotein-cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein (VLDL-C). HDL-C is involved in reverse cholesterol transport and its blood levels have been shown to be inversely correlated with cardiovascular risk. Thus, a pharmacologic agent that can elevate HDL-C has been seen as an exciting area of research. In recent studies, evacetrapib was shown to be safe and efficacious. It produced an increase in HDL-C up to 128% and a 35% decrease in LDL-C, in comparison to placebo. In addition, evacetrapib was also shown to be more potent than previous CETP inhibitors. HDL-C particles treated with evacetrapib remained functional and had improved cholesterol efflux. A previously studied CETP inhibitor, torcetrapib, exhibited side effects of hyperaldosteronism, manifesting in electrolyte disturbances, and hypertension. These detrimental effects were not seen with evacetrapib. Recently, the results of evacetrapib's phase III ACCELERATE trial showed no significant reduction in major adverse cardiovascular events or mortality, and the drug will not be marketed. Although beneficial cholesterol effects were seen with this drug, more needs to be known to understand what role, if any, evacetrapib has in the reduction of cardiovascular risk.

PS 08-38] CLINICAL UTILITY OF OPTICAL COHERENCE TOMOGRAPHY (OCT) IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD)

Objective: Chronic kidney disease (CKD) patients have a significantly increased risk of cardiovascular disease (CVD). An established association exists between vasculopathy in the kidney and eye, suggesting common pathophysiology. After correcting for CKD and classical CVD risk factors, retinopathy is associated with a higher prevalence of CVD. Optical coherence tomography (OCT) is a novel, non-invasive method of cross-sectionally imaging the retino-choroidal structures. Its use in CKD patients remains unexplored. Design and Method: We used the SPECTRALIS OCT in an exploratory study examining the retino-choroidal structures in 24 patients with hypertension, 24 with varying degrees of CKD and 25 matched healthy controls. Measurements included retinal thickness, retinal nerve fibre layer (RNFL) thickness, macular volume and choroidal thickness. Results: Retinal thickness was reduced across the outer 4 locations on the macula in CKD (p < 0.05). RNFL thickness did not differ between groups. Macular volume was lower in CKD compared to both hypertension (p < 0.0001) and health (p < 0.001). Similarly, CKD was associated with reduced choroidal compared to both hypertension (p < 0.001) and health (p < 0.01). In those with CKD, a thinner choroid was associated with a lower glomerular filtration rate (p < 0.01) and heavier proteinuria (p < 0.01), both important independent CVD risk factors. In CKD, a thinner choroid was also associated with increased plasma levels of systemic inflammatory markers (CRP, IL-6 and ET-1) and to the degree of renal histological injury. Conclusions: The decrease in retino-choroidal thickness in CKD may represent systemic microvascular injury. Thus, OCT could play a clinically significant role in assisting diagnosis of systemic microvascular disease, therapeutic intervention and identification of high-risk CVD patients.

Abstract 14373: Treatment Trends Among High Cardiovascular Disease Risk Patients Treated With Lipid-lowering Therapies: A United States Real-world Study

Introduction: Strong evidence exists linking LDL-C as a causal factor of atherosclerotic CVD. Statins are the cornerstone for lipid lowering therapy (LLT) so it is important to understand treatment trends in light of current guidelines. Objective: To evaluate LLT trends in a US real-world setting. Methods: Patients (aged ≥18y) who initiated LLT (statins and/or ezetimibe) from 01/01/2007-06/30/2011 were retrospectively identified from IMS commercial claims. Patients were classified into two cohorts: 1) Prior CVD and 2) Prior CHD RE conditions [Definitions in Figure 1] and stratified by age group (&lt;65 and ≥65y). Eligible patients had continuous health plan enrollment for ≥1 year pre- and post-index date (LLT initiation date). The following were assessed: index statin intensity (defined by ACC/AHA 2013 guidelines), first treatment modification (e.g., switch, re-initiation after temporary discontinuation of &gt;60 days, permanent discontinuation of all LLT) and time-to-first treatment modification. Results: A total of 41,934 patients with prior CVD (mean age: 58y) and 170,344 patients with CHD RE (mean age: 57y) were analyzed. From 2007-2011, 66.6-77.8% and 8.8-25.1% of the cohorts were prescribed moderate-intensity and high-intensity statins, respectively, on the index date. Among the CVD and CHD RE cohorts, 18.8% and 26.2% reinitiated index LLT, 11.6% and 13.2% permanently discontinued all LLT and 19.5% and 13.6% switched to a different statin, respectively, as the first treatment modification (Figure 1). A similar trend was observed among patients aged ≥65y. Average number of days to first treatment modification was 130-399 days. Conclusion: With 79% of patients modifying their index LLT, of which 12-13% permanently discontinuing all LLT, such treatment modifications may potentially be indicative of index statin intolerability and/or ineffectiveness. High-intensity statin therapy initiation is low, potentially resulting in residual risk of CVD.

Effect of metabolic control on oxidative stress, subclinical atherosclerosis and peripheral artery disease in diabetic patients.

IntroductionBy rising diabetes mellitus prevalence, the prevalence of its most complication; cardiovascular disease (CVD) is also increasing. Moreover, oxidative stress has important role in pathogenesis of diabetes and its complications. We investigated relationship between total antioxidant status (TAS) and surrogate measures of subclinical atherosclerosis (SA) with glycemic status in diabetics.Methods & materialsIn a cross-sectional study, we recorded height, weight, waist circumference (WC) and blood pressure of 267 subjects. Blood samples were collected to measure fasting blood sugar (FBS), glycated hemoglobin (HbA1c), lipid profiles and TAS. The surrogate measures of SA were Carotid Intima Media Thickness (CIMT), and Ankle Brachial Index (ABI).ResultsWe found significantly lower TAS leves and ABI values and higher CIMT in diabetic patients especially in poor glycemic group. There was a nonsignificant, weak correlation between TAS, ABI and CIMT with glycemic status (r = −0.10, −0.16, and +0.09, respectively). Multivariate regression analysis showed a significant influence of increasing age and diabetes duration on worsening CIMT in poor glycemic group.ConclusionsOur study showed poor glycemic control leads to worse CIMT by increasing age and duration of diabetes. However we did not find a significan correlation between glycemic status and TAS levels. We suggest CIMT measurement along with other SA markers in poor glycemic diabetics, especially in older patients with longer duration of diabetes, to identify high risk CVD patients.

Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States

Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk. To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients. Patients included were aged ≥ 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post-index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post-index. Descriptive statistics were used to report results. There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post-index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C ≥ 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C ≥ 100 mg/dL. At 1 year post-index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event. There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk.

Cardiovascular disease (CVD) risk factors among cisplatin-treated testicular cancer survivors (TCS): A multicenter clinical study of U.S. and Canadian patients.

391 Background: The remarkable success of cisplatin-based chemotherapy in curing metastatic TC has been accompanied by potential life-threatening sequelae, including CVD. Most prior studies, however, have been conducted in Europe and included older chemotherapy regimens. We examined CVD risk factors in an ongoing multi-center clinical study of TCS given modern cisplatin-based chemotherapy (CHEM) at centers in North America (NCI 1R01 CA157823-02). Methods: TCS aged ≤49 years at time of first-line CHEM were eligible to undergo clinical examination and complete a questionnaire regarding co-morbidities, lifestyle behaviors, and prescription drug use. Results: We evaluated the first 443 consecutively enrolled TCS (23% seminoma; 77% nonseminoma) with most having stage II (52%) or III (28%) disease. The median age at time of TC diagnosis was 32 years (range 15-49 years) and median time since completion of chemotherapy was 59 months (range 1-24 years). Patients were largely white (90%), married (62%), and had full-time employment (82%) and health insurance (88%). 8% of TCS were current smokers. 48% of TCS had gained &gt;10 lbs after CHEM with 29% having a ≥102 cm (40 inch) waist circumference, and 43% and 31% having a body mass index of 25 to &lt;30 kg/m2 (overweight) and ≥ 30 kg/m2 (obese), respectively. A sizable proportion of men had abnormal systolic (21% with 130-139 mm Hg and 17% with ≥140 mm Hg) and diastolic (35% with 80-89 mm Hg and 13% with ≥90 mm Hg) blood pressure. 14%, 11%, and 5% TCS indicated that they currently used medications for hypertension, cholesterol and diabetes, respectively. Cardiac conditions were reported by 32 TCS (7%), including angina (N=2), angioplasty/stent placement (N=1), myocardial infarction (N=1), transient ischemic attack (N=1), stroke (N=2), peripheral vascular disease (N=12), deep vein thrombosis (N=23), and pulmonary embolism (N=15). Conclusions: A number ofCVD risk factors are present in a contemporary North American cohort of TCS after CHEM. Future analytic studies should focus on mechanistic investigations to facilitate the development of screening and preventive efforts for CVD in high-risk patients.

Bedtime hypertension chronotherapy: concepts and patient outcomes.

Recent findings indicate cardiovascular disease (CVD) risk is best predicted by asleep systolic blood pressure (SBP), and lowering it by scheduling ≥1 conventional long-acting hypertension medications, alone or in combination, at bedtime significantly lessens vascular-associated risks. Some 20 years ago, four controlled-onset extended-release drug-delivery systems incorporating a calcium channel or β-blocker, with the treatment goal specifically being attenuation of morning rather than asleep BP, were conceived as one type of bedtime hypertension chronotherapy. However, the CONVINCE outcomes trial failed to substantiate the merit of targeting morning and daytime BP to decrease CVD risk. The HOPE trial, entailing bedtime ramipril treatment for high CVD risk patients, showed substantial reduction of vascular-related events, theorized as the beneficial treatment-time-dependent strong asleep BP lowering. The MAPEC trial was the first prospective randomized treatment-time outcomes investigation to test the worthiness of bedtime hypertension chronotherapy entailing ≥1 conventional long-acting medications (BTCT), in comparison to the conventional morning-time therapeutic scheme for all medications (CMTT), to normalize asleep BP and diminish CVD risk. BTCT compared to CMTT significantly better lowered asleep BP and most importantly major CVD-associated morbidity and mortality, including myocardial infarction and ischemic and hemorrhagic stroke, by ~60%. CVD risk reduction was strongest when the BTCT included an angiotensin receptor blocker. The HOPE and MAPEC trials provide positive evidence of very significant CVD risk reduction by a BTCT strategy that specifically targets normalization of asleep BP, evidence that awaits conformation by the ongoing Hygia and other outcomes trials.