Coronary Heart Disease Risk Equivalent Research Articles

Statin Use and Major Adverse Cardiac Events among High Cardiac Risk Patients with Lung Cancer Receiving Radiotherapy

Statin use is recommended in patients with high Framingham risk or established coronary heart disease (CHD). Patients with lung cancer have a high prevalence of pre-existing CHD and face excess cardiac risk following thoracic radiotherapy (RT). We sought to characterize statin use by cardiac risk in a large cohort of patients with locally advanced non-small cell lung cancer (NSCLC) treated with RT. Retrospective analysis of 748 locally advanced NSCLC patients treated with thoracic RT. Patients were stratified by 10-year Framingham risk. High cardiac risk was defined as either high (≥20%) Framingham risk or pre-existing CHD or CHD risk equivalent. The cumulative incidence of major adverse cardiac events (MACE; unstable angina, heart failure, myocardial infarction [MI], coronary revascularization, and cardiac death) was estimated and Fine and Gray regressions were performed (non-cardiac death as a competing risk). The median follow-up was 20 months overall and 48 months in patients alive. Among CHD-negative patients (64.2%), 27.9% were low Framingham risk, 25.0% moderate and 47.1% high risk. At the time of RT, statin use by Framingham risk group (low, moderate, or high) or known CHD was 15.7%, 25.8%, 37.2%, and 63.1%, respectively. Among all high cardiac risk patients (66%, n = 496), only 51.2% were on a statin at the time of RT. High cardiac risk patients on statins (compared to no statin) were more likely to have a history of hypertension (73.3% vs. 51.4%, P<.001), hyperlipidemia (83.4% vs. 29.2%, P<.001), diabetes (28.1% vs. 11.5%, P<.001), former smoking (62.1% vs. 49.4%, P = .017), peripheral vascular disease (17.1 vs. 7.4%, P = .001), stroke (4.4% vs. 1.2%, P = .032), coronary artery disease (52.2% vs. 32.5%, P<.001), MI (49.6% vs. 26.0%, P = .001), and congestive heart failure (17.8% vs. 6.6%, P<.001), with no significant difference in age, sex, performance status, cancer stage, chemotherapy use, RT prescription dose, or cardiac or coronary RT dose exposure (P>.05). Statin use was associated with increased risk of MACE in high cardiac risk patients on univariable analysis (hazard ratio [HR] 1.76; 95% CI: 1.06-2.90; P = .027) with 2-year MACE estimates of 10.9% vs. 4.5%, but not when adjusted for known cardiac prognostic factors (P = 0.4). Only half of statin-eligible high cardiac risk patients with locally advanced NSCLC are on a statin at the time of RT. Even among high cardiac risk patients, those on statins harbored significantly more cardiac risk factors than those not on statins, suggesting only those of highest cardiac risk are on anti-lipid therapy at the time of RT. These results highlight that NSCLC patients represent a distinctly high cardiac risk population due to elevated baseline risk factors and cardiac radiation exposure with an unmet need for improved cardiac risk reduction, including optimization of medical therapy.

Nontraditional Biomarkers for Cardiovascular Disease in Patients With Chronic Kidney Disease

Cardiovascular disease (CVD) is the leading cause of death among patients who have chronic kidney disease (CKD). Nowadays, CKD per se is considered one of the coronary heart disease (CHD) risk equivalents. Apart from traditional CVD risk factors, there are several possible determinants for CVD in patients with CKD, for example, uremic toxins, increased inflammatory stage, abnormal bone mineral metabolism, and positive calcium balance. In this narrative review, we offer a summary of the extensively studied biomarkers for CVD in patients with CKD, including uremic toxins (p-cresol, indoxyl sulfate, and advanced glycated end products), and a novel indicator of arterial stiffness, cardio-ankle vascular index (CAVI), which is an independent prognostic predictor for CVD. For the uremic toxins, we reviewed their metabolisms, particularly, how the reduced renal function in CKD patients affect their clearance and their clearance with dialysis. Also, we pay attention to the recent evidence on how those uremic toxins contribute to CVD and their clinical associations. We do not include the possible treatment targeting at those uremic toxins. As for the novel indicator of arterial stiffness, we reviewed the clinical application of CAVI in comparison to the standard indicator for arterial stiffness, pulse wave velocity.&#x0D;

Lipid-lowering Drugs and Neurocognitive Function: A Systematic Review.

Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials. A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function. Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo. Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed.

Peripheral Artery Disease and African Americans: Review of the Literature

Peripheral artery disease (PAD) is a chronic, obstructive disease of the peripheral vasculature which is a coronary heart disease risk equivalent. African Americans (AA) are at the highest risk for developing this disease at every age group. The purpose of this review is to shed light on the risk factors for PAD and their implications for disease manifestation in AA, and to highlight ways to combat these known racial disparities in order to achieve cardiovascular health equity in this population. Even after controlling for differences in the prevalence of known cardiovascular risk factors, AA are still significantly more likely to have PAD. In part, due to a disproportionate amount of cardiovascular risk factors and detrimental socioeconomic factors, AA with PAD have a worse prognosis and more unfavorable outcomes than other ethnic groups with PAD. AA with PAD are more likely to have limb loss with amputation and less likely to receive revascularization leading to limb salvage. Advanced age, cigarette smoking, diabetes, hypertension, hyperlipidemia, chronic kidney disease, and poor socioeconomic status or education level have all been associated with increased risk of PAD. AA have a higher likelihood of having many, but not all, of these conditions. Nevertheless, increased cardiovascular risk for PAD combined with a relative lack of awareness about the disease in the AA community leads to poor health outcomes. Targeted interventions that partner healthcare access and delivery in community-based, non-traditional health care settings as well as the traditional clinics and hospitals may prove to be a more successful means of outreach in this high-risk population.

Bempedoic Acid a Small Molecule Drug Process and Synthesis, Innovation And /Or Advantages, Development Status And /Or Regulatory Status

The current standard of care for patients with hypercholesterolaemia is primarily statins which can reduce LDL-C. However, some patients, particularly those with heterozygous familial hypercholesterolaemia, coronary heart disease (CHD), CHD-risk equivalents, and other clinical manifestations of atherosclerotic cardiovascular disease [1] (ASCVD), require additional LDL cholesterol lowering on top of what can be achieved with maximum tolerated statin therapy.

Cardiac Events after Radiation Therapy (RT) for Stage II-III Non-Small Cell Lung Cancer (NSCLC): Analysis of 748 Patients

Radiation therapy-associated cardiac toxicity in patients with NSCLC arises sooner and is of greater clinical significance than historically appreciated. Recent studies have been limited by inconsistent definitions and small size. This study reports major cardiac events after RT in a large cohort of patients with NSCLC using comprehensive, validated cardiac toxicity criteria and dose-volume data. Retrospective study of 748 patients with Stage II (9%) to III (91%) NSCLC treated with 3D-conformal (77%) or intensity-modulated (22%) RT (median dose, 64 Gy) and chemotherapy (61%), chemotherapy and surgery (33%), or RT alone (4%) between 1998–2014 at one institution. Hearts were re-contoured per cardiac atlas definitions. Patients without baseline coronary heart disease (CHD) or CHD risk equivalent were stratified by Framingham risk. Primary endpoint was major cardiac events, defined as any grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, v4.03) or Major Adverse Cardiac Events (MACE). Estimates of Kaplan-Meier overall survival (OS) and cumulative incidence of cardiac events (non-cardiac death as a competing risk) were calculated. Fine and Gray and Cox regressions were performed. Median follow up from RT was 1.9 years. Median mean heart dose was 12.3 Gy. Two-year OS stratified by low, moderate, or high Framingham risk group or known CHD was 62.7%, 56.0%, 47.0%, and 46.8%, respectively (P=.001). Median time to first major cardiac event was 10.4 months; cumulative incidence at 1, 2, and 5-years was 18.2%, 23.5%, and 32.4%, respectively. Two-year cumulative incidence of major cardiac events (conduction, 12.0%; heart failure, 5.7%; MACE, 4.8%; pericardial [all], 4.7%; pericardial [effusion, cytology benign], 1.8%; coronary/ischemic, 2.5%; valvular, 1.1%; and cardiopulmonary/other, 5.4%) was increased in patients with vs without baseline CHD (31.2% vs 18.9%; P<.0001) and those with mean heart dose >12 Gy vs ≤12 Gy (26.7% vs 19.3%; P=.009), respectively. On multivariable analysis (MVA), baseline CHD (hazard ratio [HR] 1.75, 95% CI 1.35–2.28; P<.0001) and mean heart dose (HR 1.09/5 Gy, 95% CI 1.02–1.16; P=.013) were significantly associated with major cardiac events. On MVA accounting for baseline CHD and known lung cancer prognostic factors, major cardiac events were significantly associated with decreased OS (HR 2.91, 95% CI 2.39–3.55; P<.0001), while mean heart dose was not (HR 1.04/5 Gy, 95% CI 0.99–1.09; P=.107). In this large cohort of patients with NSCLC, major cardiac events were common, occurred sooner than previously reported, and were associated with baseline CHD and heart dose. These results build upon recent reports, support efforts to minimize heart irradiation, and highlight the importance of pre-treatment cardiac risk assessment and development of risk mitigation strategies for high risk patients.

Evaluation of Lipid Profile and Residual Cardiovascular Risk in Patients Prior to Initiation of Niaspan Therapy

Background: Despite significant impact of statins, there are a number of patients with residual risk of cardio vascular disease who have optimally controlled low-density lipoprotein cholesterol (LDL-C). Niaspan (extended-release nicotinic acid or niacin-ER) is indicated for its use as monotherapy for the treatment of very high triglyceride (TG) levels and for the raising of high-density lipoprotein cholesterol (HDL-C) representing those residual risk populations. The patient characteristics and lipid profile, prior to initiation of therapy, in the real-world clinical setting has not been well documented. Objectives: This study evaluated lipid levels among patients initiating Niaspan in real-world clinical practice. Methods: Patients with a first prescription of Niaspan were identified using electronic medical record data from GE. Lipid values were categorized into optimal and nonoptimal TG or HDL-C levels. Results: There were 89 091 new users. Most patients had nonoptimal TG, HDL-C, TG/HDL-C ratio, LDL-C, and non-HDL-C levels. Among those with nonoptimal TG and HDL, the ratio of TG to HDL-C was higher among younger age groups (mean ratio 12.0 in males; 10.58 in females aged 18 to &lt;40 years). TG was significantly correlated with non-HDL-C (0.41, P &lt; .001) but not with LDL-C. Among those with LDL-C &lt;100 mg/dL, 64.3% had nonoptimal TG/HDL-C ratio and approximately 70% had non-HDL-C ≥130 mg/dL. More than a third of the patients had diagnosis of coronary heart disease or coronary heart disease risk equivalent. Conclusion: Majority of Niaspan users had nonoptimal TG and/or HDL-C. The correlation of nonoptimal TG levels with non-HDL-C levels further support that Niaspan was targeted to population with residual risk for cardiovascular disease.

Lipid management in India: a nationwide, cross-sectional physician survey

BackgroundCurrent international guidelines on dyslipidemia are not concordant on various aspects of management. Also, there are no uniformly accepted Indian guidelines. We, therefore, performed a physician survey to understand lipid management practices in India.MethodsAn anonymous survey questionnaire was administered to gauge physicians’ self-reported behavior regarding lipid management aspects. Results were expressed in terms of percentages based on the number of responses obtained.ResultsA total of 404 physicians participated in the survey. Eighty-eight percent respondents ordered a lipid profile before starting statin therapy, and 80% preferred to set lipid targets, though the tools used for calculating cardiovascular risk varied. Atorvastatin was preferred over rosuvastatin in primary prevention (72.9 vs. 32.4%), secondary prevention (54.6 vs. 46.7%), diabetic patients (56.3 vs. 40.3%) and post-ACS (78.3 vs. 34%). High-intensity statins were preferred by 73.7% of respondents in post-ACS cases. Fifty percent doctors chose not to use a statin in diabetic patients, irrespective of their LDL-C levels. The most preferred drug option for managing atherogenic dyslipidemia and moderate hypertriglyceridemia was statin-fibrate combination (55.1%) and fibrates (35.4%), respectively. Sixty-three percent doctors preferred to prescribe statins in patients with moderately high LDL-C and normal triglycerides, without CHD or CHD risk equivalents. Around 28% of doctors preferred not to use pharmacotherapy for managing isolated low HDL. Of the participants, 73% used fibrates in ≤20% of their dyslipidemic patients, with fenofibrate being the most preferred (90.5%). Ezetimibe was mainly used in patients with uncontrolled LDL-C despite statin therapy (52.4% respondents). Most preferred approaches to manage statin intolerance included reducing statin dose (39%) and stopping and restarting statins at a lower dose (34.5%). Fifty-two percent of doctors chose not to alter pre-existing therapy in patients who had LDL-C levels at goal but elevated non-HDL-C levels.ConclusionThis is the first survey in India that provides useful insights into Indian physicians’ self-reported perspectives on managing dyslipidemia in routine clinical practice. Despite concordance with the currently available guidelines in certain aspects, there is incongruence in managing specific dyslipidemia problems. Further continuing medical education and the development of evidence-based, India-specific lipid guidelines can help reduce some of these differences.

Diabetes, diabetes severity, and coronary heart disease risk equivalence: REasons for Geographic and Racial Differences in Stroke (REGARDS)

Evidence is mixed regarding whether diabetes confers equivalent risk of coronary heart disease (CHD) as prevalent CHD. We investigated whether diabetes and severe diabetes are CHD risk equivalents. At baseline, participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study (black and white US adults ≥45 years old recruited in 2003-2007) were categorized as having prevalent CHD only (self-reported or electrocardiogram evidence; n = 3,043), diabetes only (self-reported or elevated glucose; n = 4,012), diabetes and prevalent CHD (n = 1,529), and neither diabetes nor prevalent CHD (n = 17,155). Participants with diabetes using insulin and/or with albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g) were categorized as having severe diabetes. Participants were followed up through 2011 for CHD events (myocardial infarction or fatal CHD). During a mean follow-up of 5 years, 1,385 CHD events occurred. The hazard ratios of CHD events comparing participants with diabetes only, diabetes, and prevalent CHD and neither diabetes nor prevalent CHD with those with prevalent CHD were 0.65 (95% CI 0.54-0.77), 1.54 (95% CI 1.30-1.83), and 0.41 (95% CI 0.35-0.47), respectively, after adjustment for demographics and risk factors. Compared with participants with prevalent CHD, the hazard ratio of CHD events for participants with severe diabetes was 0.88 (95% CI 0.72-1.09). Participants with diabetes had lower risk of CHD events than did those with prevalent CHD. However, participants with severe diabetes had similar risk to those with prevalent CHD. Diabetes severity may need consideration when deciding whether diabetes is a CHD risk equivalent.

Work productivity loss and indirect costs associated with new cardiovascular events in high-risk patients with hyperlipidemia: estimates from population-based register data in Sweden.

ObjectivesTo estimate productivity loss and associated indirect costs in high-risk patients treated for hyperlipidemia who experience cardiovascular (CV) events.MethodsRetrospective population-based cohort study conducted using Swedish medical records linked to national registers. Patients were included based on prescriptions of lipid-lowering therapy between 1 January 2006 and 31 December 2011 and followed until 31 December 2012 for identification of CV events and estimation of work productivity loss (sick leave and disability pension) and indirect costs. Patients were stratified into two cohorts based on CV risk level: history of major cardiovascular disease (CVD) and coronary heart disease (CHD) risk equivalent. Propensity score matching was applied to compare patients with new events (cases) to patients without new events (controls). The incremental effect of CV events was estimated using a difference-in-differences design, comparing productivity loss among cases and controls during the year before and the year after the cases’ event.ResultsThe incremental effect on indirect costs was largest in the CHD risk equivalent cohort (n = 2946) at €3119 (P value <0.01). The corresponding figure in the major CVD history cohort (n = 4508) was €2210 (P value <0.01). There was substantial variation in productivity loss depending on the type of event. Transient ischemic attack and revascularization had no significant effect on indirect costs. Myocardial infarction (€3465), unstable angina (€2733) and, most notably, ischemic stroke (€6784) yielded substantial incremental cost estimates (P values <0.01).ConclusionsIndirect costs related to work productivity losses of CV events are substantial in Swedish high-risk patients treated for hyperlipidemia and vary considerably by type of event.

Medical costs associated with cardiovascular events among high-risk patients with hyperlipidemia.

ObjectivesThis study descriptively examined acute and longer term direct medical costs associated with a major cardiovascular (CV) event among high-risk coronary heart disease risk-equivalent (CHD-RE) patients. It also gives a firsthand look at fatal versus nonfatal CV events.MethodsThe MarketScan® Commercial Claims and Encounters Database was used to identify adults with a CV event in 2006–2012 with hyperlipidemia or lipid-lowering therapy use in the 18 months prior to one of the following inpatient CV events: myocardial infarction, ischemic stroke, unstable angina, transient ischemic attack, percutaneous coronary intervention, or coronary artery bypass graft (CABG). Patients were required to have a preindex diagnosis of at least one of the following: peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease, or diabetes. A subset analysis was conducted with patients with data linkable to the Social Security Administration Master Death File. Direct medical costs were reported for each quarter following a CV event, for up to 36 months after the first CV event.ResultsIn total, 38,609 CHD-RE patients were included, mean age 57 years, 31% female. CABG, myocardial infarction, and percutaneous coronary intervention were the most frequent and most expensive first CV events, accounting for >75% of all first CV events with mean first quarter costs ranging from $17,454 (nonfatal transient ischemic attack) to $125,690 (fatal CABG). Overall, 15% of those with a first CV event went on to have a second event during the 36-month study period with mean first quarter nonfatal and fatal costs similar to first event levels. Third CV events were rare, happening in less than 3% of patients.ConclusionCV events among CHD-RE patients were costly regardless of sequence, averaging $47,433 in the first 90 days following an event and remaining high, never returning to preevent levels. When fatal, first CV event costs were 1.2 to 2.9 times higher than when nonfatal.

Abstract 250: Real-world Rates and Costs of Heart Failure Events Among Patients with Hyperlipidemia

Background: This real-world retrospective cohort study estimated the rate of heart failure events and total healthcare costs among patients with hyperlipidemia. Methods: Patients (aged 18-64 years) with hyperlipidemia diagnosis and/or lipid-lowering medications were identified from the HealthCore Integrated Research Database SM from 1/1/2007 to 12/31/2008 and followed until 2/28/2013. Patients were stratified by cardiovascular (CV) risk level as (1) secondary prevention with a history of myocardial infarction, stroke, unstable angina, or revascularization, (2) modified coronary heart disease (CHD) risk equivalent (RE) without a history of CV events but with peripheral artery disease, type 2 diabetes, abdominal aortic aneurysm, ischemic heart disease, stable angina, or TIA, and (3) primary prevention without a history of CV events or CHD RE. Patients with new CV event hospitalization during follow-up were propensity score-matched to patients without new CV events within each cohort. Proportion of patients with heart failure events and incremental total costs during 2 years of follow-up were evaluated. Results: Before matching, 62,427 patients had ≥1 CV event (13.2% secondary prevention, 38.4% CHD RE, 48.5% primary prevention). For patients with ≥1 CV event during follow-up, 38.8% of secondary prevention, 42.6% of CHD RE, and 30.0% of primary prevention had heart failure as their index event. Of patients with heart failure index event, 58.3% of secondary prevention, 47.3% of CHD RE, and 30.5% of primary prevention patients had 1 or more heart failure events over 2 years. Among patients with ≥1 heart failure events, 36.2% of secondary prevention, 30.0% of CHD RE, and 17.7% of primary prevention patients had ≥3 heart failure events over 2 years. Among matched patients (85-87% of patients), incremental total cost over 2 years for patients with heart failure as their index event compared with patients without CV events was $56,078 for secondary prevention, $53,247 for CV RE, and $49,637 for primary prevention cohorts. Conclusions: The rate and recurrence of heart failure among hyperlipidemic patients is very high and the long term healthcare costs substantial in this real-world 2-year study.

Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study

The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia. This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis). At week 24, estimated mean (95% CI) changes in LDL-C from baseline were -48.2% (-52.0% to -44.4%) and -2.3% (-7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of -45.9% (-52.5% to -39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups. Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

THE YIELD AND PROGNOSTIC VALUE OF SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT) MYOCARDIAL PERFUSION IMAGING (MPI) IN PATIENTS WITH END-STAGE LIVER DISEASE (ESLD) IN THE PRE-OPERATIVE SETTING: ABNORMAL TESTS DO NOT PREDICT SHORT OR MEDIUM-TERM MORTALITY

CKD is an independent risk factor for development of coronary heart disease (CHD), and is considered a CHD risk equivalent. The value of SPECT MPI in screening for ischemia and assessing pre-operative risk is poorly defined in patients with CKD. Our institutional stress database was queried for

Preventing Cardiovascular Disease in Patients with Diabetes: Use of Aspirin for Primary Prevention

Diabetics are at high risk for atherosclerotic cardiovascular disease (ASCVD) and are considered a coronary heart disease risk equivalent. The utility of aspirin in primary prevention of ASCVD in diabetic patients has been widely studied and is still debated. Overall, the current evidence suggests a modest benefit for reduction in ASCVD events with the greatest benefit among those with higher baseline risk, but at the cost of increased risk of gastrointestinal bleeding. Diabetic patients at higher risk (with 10-year ASCVD risk >10%) are generally recommended for aspirin therapy if bleeding risk is felt to be low. A patient-provider discussion is recommended before prescribing aspirin therapy. Novel markers such as coronary artery calcium scores and high-sensitivity C-reactive protein may help refine ASCVD risk prediction and guide utility for aspirin therapy. This article will review the literature for the most up-to-date studies evaluating aspirin therapy for primary prevention of ASCVD in patients with diabetes.

Is inflammatory chronic obstructive pulmonary disease a coronary heart disease risk equivalent? A longitudinal analysis of the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.

BackgroundEvidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD). An important etiological link between COPD and CHD may be an underlying systemic inflammatory process. Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation.MethodsLongitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988–1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included. Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD. A novel “inflammatory” COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L).ResultsThe risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90). Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD). After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated. For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group.ConclusionsOur study did not confirm that inflammatory COPD may be a CHD risk equivalent. However, due to the small size of the “inflammatory” COPD group, further prospective replication and validation is needed. Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation.

Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.

Lipid attainment among patients newly treated with lipid-altering drugs

Objective:Guidelines for preventing and treating patients with coronary artery disease have traditionally focused on reducing low-density lipoprotein cholesterol (LDL-C). Current treatments are effective; however, previous studies have identified a significant proportion of patients that are not achieving the recommended lipid levels. New guidelines were introduced November 2013. The objective of this study was to examine recent practice patterns and factors related to initiating treatment for hypercholesterolemia, which provides a comparative baseline to the introduction of new guidelines.Research design and methods:We conducted a retrospective cohort analysis utilizing laboratory results of lipid profiles and medical claims from January 2007 to September 2011 to identify patients with elevated LDL-C and diagnoses of hypercholesterolemia without prior pharmacotherapy. Pharmacotherapy dispensed, treatment modifications, LDL-C-goal attainment, and potential drug intolerance were evaluated.Results:Overall, among newly treated patients, 70.9% achieved the recommended LDL-C level within the first year of treatment; however, only 19.4% of those with coronary heart disease (CHD) or CHD risk equivalents achieved the more aggressive LDL-C goal of <70 mg/dL (1.8 mmol/L). LDL-C goals were generally achieved with the use of statins; however, a majority of patients underwent treatment modification(s) (e.g., discontinuation or restart). More than half of the patients diagnosed with elevated LDL-C did not initiate pharmacotherapy.Limitations:Data was unavailable for inpatient hospitalizations, family history of cardiovascular diseases, body weight, and height, and likely under-reporting of smoking within claims data.Conclusions:Newly treated patients with elevated LDL-C results generally achieved the recommended and risk-specific LDL-C goal with the use of lipid-altering drugs; however, there still exists a notable population of patients with CHD or CHD risk equivalents who were not treated to goal and a significant number of patients who do not receive lipid-lowering pharmacotherapy. New therapies and prescribing practices are warranted to adequately address these two patient populations.

Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.

Potential Effects of Reclassifying CKD as a Coronary Heart Disease Risk Equivalent in the US Population

Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. Nationally representative cross-sectional study. 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4million meriting therapy initiation and intensification, respectively. CKD and LDL cholesterol defined using a single laboratory value. Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy.