Nearly 10 million US adults experience stable angina, which occurs when myocardial oxygen supply does not meet demand, resulting in myocardial ischemia. Stable angina is associated with an average ...annual risk of 3% to 4% for myocardial infarction or death. Diagnostic tests and medical therapies for stable angina have evolved over the last decade with a better understanding of the optimal use of coronary revascularization.
Coronary computed tomographic angiography is a first-line diagnostic test in the evaluation of patients with stable angina due to higher sensitivity and comparable specificity compared with imaging-based stress testing. Moreover, coronary computed tomographic angiography allows detection of nonobstructive atherosclerosis that would not be identified with other noninvasive imaging modalities, improving risk assessment and potentially triggering more appropriate allocation of preventive therapies. Novel therapies treating lipids (proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, and icosapent ethyl) and type 2 diabetes (sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists) have improved cardiovascular outcomes in patients with stable ischemic heart disease when added to usual care. Randomized clinical trials showed no improvement in the rates of mortality or myocardial infarction with revascularization (largely by percutaneous coronary intervention) compared with optimal medical therapy alone, even in the setting of moderate to severe ischemia. In contrast, revascularization provides a meaningful benefit on angina and quality of life compared with antianginal therapies. Measures of the effect of angina on a patient's quality of life should be integrated into the clinic encounter to assist with the decision to proceed with revascularization.
For patients with stable angina, emphasis should be placed on optimizing lifestyle factors and preventive medications such as lipid-lowering and antiplatelet agents to reduce the risk for cardiovascular events and death. Antianginal medications, such as β-blockers, nitrates, or calcium channel blockers, should be initiated to improve angina symptoms. Revascularization with percutaneous coronary intervention should be reserved for patients in whom angina symptoms negatively influence quality of life, generally after a trial of antianginal medical therapy. Shared decision-making with an informed patient is important for effective treatment of stable angina.
Objectives The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. Background LDL-C is routinely estimated by the ...Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients. Methods We examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl. Results Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl). Conclusions The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥70 mg/dl, and therefore additional evaluation is warranted in high-risk patients.
All we need to know about lipoprotein(a) Bess, Courtney; Mehta, Anurag; Joshi, Parag H.
Progress in cardiovascular diseases,
05/2024, Letnik:
84
Journal Article
Recenzirano
Lipoprotein(a) Lp(a), a genetically determined macromolecular complex, is independently and causally associated with atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis via ...proposed proinflammatory, prothrombotic, and proatherogenic mechanisms. While Lp(a) measurement standardization issues are being resolved, several guidelines now support testing Lp(a) at least once in each adult's lifetime for ASCVD risk prediction which can foster implementation of more aggressive primary or secondary prevention therapies. Currently, there are several emerging targeted Lp(a) lowering therapies in active clinical investigation for safety and cardiovascular benefit among both primary and secondary prevention populations. First degree relatives of patients with high Lp(a) should be encouraged to undergo cascade screening. Primary prevention patients with high Lp(a) should consider obtaining a coronary calcium score for further risk estimation and to guide further ASCVD risk factor management including consideration of low dose aspirin therapy. Secondary prevention patients with high Lp(a) levels should consider adding PCSK9 inhibition to statin therapy.
Elevated lipoprotein(a) (Lpa) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.
The aim ...of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.
Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.
Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio HR: 1.17; 95% confidence interval CI: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.
Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.
The role of inflammation in the propagation of atherosclerosis and susceptibility to cardiovascular (CV) events is well established. Of the wide array of inflammatory biomarkers that have been ...studied, high-sensitivity C-reactive protein (hsCRP) has received the most attention for its use in screening and risk reclassification and as a predictor of clinical response to statin therapy. Although CRP is involved in the immunologic process that triggers vascular remodeling and plaque deposition and is associated with increased CV disease (CVD) risk, definitive randomized evidence for its role as a causative factor in atherothrombosis is lacking. Whether measurement of hsCRP levels provides consistent, clinically meaningful incremental predictive value in risk prediction and reclassification beyond conventional factors remains debated. Despite publication of guidelines on the use of hsCRP in CVD risk prediction by several leading professional organizations, there is a lack of clear consensus regarding the optimal clinical use of hsCRP. This article reviews 4 distinct points from the literature to better understand the current state and application of hsCRP in clinical practice: 1) the biology of hsCRP and its role in atherosclerosis; 2) the epidemiological association of hsCRP with CVD; 3) the quality of hsCRP as a biomarker of risk; and 4) the use of hsCRP as a tool to initiate or tailor statin therapy. Furthermore, we highlight recommendations from societies and important considerations when using hsCRP to guide treatment decisions in the primary prevention setting.
Metabolic syndrome (MetS) is characterized by adiposity and atherogenic dyslipidemia consisting of elevated triglyceride and decreased high density lipoprotein cholesterol (HDL-C) levels however, ...cholesterol concentration alone does not reflect HDL functionality. Cholesterol efflux capacity (CEC) captures a key anti-atherosclerotic function of HDL; studies linking CEC to MetS have yielded inconsistent findings and lacked racial/ethnic diversity. The aim of this study was to evaluate the association between CEC and MetS in a large multi-ethnic population utilizing two different CEC assays interrogating overlapping but distinct reverse cholesterol transport pathways. A cross-sectional study was performed using the Dallas Heart Study cohort and cholesterol efflux was measured with radiolabeled and fluorescent cholesterol assays. The relationship between CEC and MetS was assessed using multivariable regression analyses. A total of 2241 participants were included (mean age was 50 years; 38% men and 53% Blacks). CEC was independently and inversely associated with MetS irrespective of efflux assay (CEC-radiolabeled, adjusted OR 0·71 95% CI 0·65-0·80. CEC-fluorescent, adjusted OR 0·85 95% CI 0·77-0·94). Both CEC measures were inversely associated with waist circumference and directly associated with HDL-C but not with other MetS components. There was an interaction by sex but not by race such that the inverse associations between CEC and MetS were somewhat attenuated in men (OR 0·86, 95%CI 0·74-1·01). In this large multi-ethnic cohort, impaired CEC is linked to MetS irrespective of efflux assay and race/ethnicity but less so among men. Future studies are needed to assess whether CEC mediates the atherosclerotic cardiovascular disease risk of MetS.
Abstract Coronary artery calcium (CAC) scanning is a reliable, noninvasive technique for estimating overall coronary plaque burden and for identifying risk for future cardiac events. Arthur Agatston ...and Warren Janowitz published the first technique for scoring CAC scans in 1990. Given the lack of available data correlating CAC with burden of coronary atherosclerosis at that time, their scoring algorithm was remarkable, but somewhat arbitrary. Since then, a few other scoring techniques have been proposed for the measurement of CAC including the Volume score and Mass score. Yet despite new data, little in this field has changed in the last 15 years. The main focus of our paper is to review the implications of the current approach to scoring CAC scans in terms of correlation with the central disease – coronary atherosclerosis. We first discuss the methodology of each available scoring system, describing how each of these scores make important indirect assumptions in the way they account (or do not account) for calcium density, location of calcium, spatial distribution of calcium, and microcalcification/emerging calcium that might limit their predictive power. These assumptions require further study in well-designed, large event-driven studies. In general, all of these scores are adequate and are highly correlated with each other. Despite its age, the Agatston score remains the most extensively studied and widely accepted technique in both the clinical and research settings. After discussing CAC scoring in the era of contrast enhanced coronary CT angiography, we discuss suggested potential modifications to current CAC scanning protocols with respect to tube voltage, tube current, and slice thickness which may further improve the value of CAC scoring. We close with a focused discussion of the most important future directions in the field of CAC scoring.
Cholesterol efflux capacity (CEC), which is a key step in the reverse cholesterol transport pathway, is independently associated with atherosclerotic cardiovascular disease (ASCVD). However, whether ...it predicts ASCVD beyond validated novel risk markers is unknown.
This study assessed if CEC improved ACSVD risk prediction beyond using coronary artery calcium (CAC), family history (FH), and high-sensitivity C-reactive protein (hs-CRP).
CEC, CAC, self-reported FH, and hs-CRP were assessed among participants without baseline ASCVD who were enrolled in the Dallas Heart Study (DHS). ASCVD was defined as a first nonfatal myocardial infarction (MI) or stroke, coronary revascularization, or cardiovascular death, assessed over a median 9.4 years. Risk prediction was assessed using various modeling techniques and improvements in the c-statistic, the integrated discrimination index (IDI), and the net reclassification index (NRI).
The mean age of the population (N = 1,972) was 45 years, 52% had CAC (>0), 31% had FH, and 58% had elevated hs-CRP (≥2 mg/l). CEC greater than the median was associated with a 50% reduced incidence of ASCVD in those with CAC (5.4% vs. 10.5%; p = 0.003), FH (5.8% vs. 10%; p = 0.05), and elevated hs-CRP (3.8% vs. 7.9%; p = 0.004). CEC improved all metrics of discrimination and reclassification when added to CAC (c-statistic, p = 0.004; IDI, p = 0.02; NRI: 0.38; 95% confidence interval CI: 0.13 to 0.53), FH (c-statistic, p = 0.006; IDI, p = 0.008; NRI: 0.38; 95% CI: 0.13 to 0.55), or elevated hs-CRP (c-statistic p = 0.008; IDI p = 0.02; NRI: 0.36; 95% CI 0.12 to 0.52).
CEC improves ASCVD risk prediction beyond using CAC, FH, and hs-CRP and warrants consideration as a novel ASCVD risk marker.
Elevated lipoprotein(a) Lp(a) and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in ...combination.
This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk.
Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor–adjusted Cox regression models.
Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS.
Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.
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