Atherosclerotic Cardiovascular Disease Event Rates Research Articles

RELATIONSHIP BETWEEN PERCENTAGE REDUCTION IN LOW-DENSITY LIPOPROTEIN CHOLESTEROL LEVELS AND MAJOR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AMONG PATIENTS TREATED WITH STATINS +/- ALIROCUMAB OR EZETIMIBE IN THE PHASE 3 ODYSSEY TRIALS

ACC/AHA 2013 guidelines for atherosclerotic cardiovascular disease (ASCVD) recommend use of statins to achieve 30 to ≥50% reduction in LDL-C. We assessed the relationship of additional LDL-C % reduction and ASCVD event rates in patients (most on maximally tolerated statins ± ezetimibe [EZE] at

Primary Prevention With Statins: ACC/AHA Risk-Based Approach Versus Trial-Based Approaches to Guide Statin Therapy

BackgroundGuidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. ObjectivesThis study compared these approaches in a direct head-to-head fashion in a contemporary population. MethodsThe study used the CGPS (Copenhagen General Population Study) with 37,892 subjects aged 40 to 75 years recruited in 2003 to 2008, all free of ASCVD, diabetes, and statin use at baseline. ResultsAmong the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC/AHA risk-based approach, the net reclassification index for eligibility for statin therapy among 40- to 75-year-old subjects from the CGPS was –0.21 for the trial-based approach and –0.13 for the hybrid approach. ConclusionsThe clinical performance of the ACC/AHA risk-based approach for primary prevention of ASCVD with statins was superior to the trial-based and hybrid approaches. Our results indicate that the ACC/AHA guidelines will prevent more ASCVD events than the trial-based and hybrid approaches, while treating fewer people compared with the trial-based approach.

Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis)

BackgroundThe American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy. ObjectivesThis study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not. MethodsMESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment. We excluded 1,100 participants (16%) on lipid-lowering medication, 87 (1.3%) without low-density lipoprotein levels, 26 (0.4%) with missing risk factors for calculation of 10-year risk of ASCVD, 633 (9%) >75 years of age, and 209 (3%) with low-density lipoprotein <70 mg/dl from the analysis. ResultsThe study population consisted of 4,758 participants (age 59 ± 9 years; 47% males). A total of 247 (5.2%) ASCVD and 155 (3.3%) hard coronary heart disease events occurred over a median (interquartile range) follow-up of 10.3 (9.7 to 10.8) years. The new ACC/AHA guidelines recommended 2,377 (50%) MESA participants for moderate- to high-intensity statins; the majority (77%) was eligible because of a 10-year estimated ASCVD risk ≥7.5%. Of those recommended statins, 41% had CAC = 0 and had 5.2 ASCVD events/1,000 person-years. Among 589 participants (12%) considered for moderate-intensity statin, 338 (57%) had a CAC = 0, with an ASCVD event rate of 1.5 per 1,000 person-years. Of participants eligible (recommended or considered) for statins, 44% (1,316 of 2,966) had CAC = 0 at baseline and an observed 10-year ASCVD event rate of 4.2 per 1,000 person-years. ConclusionsSignificant ASCVD risk heterogeneity exists among those eligible for statins according to the new guidelines. The absence of CAC reclassifies approximately one-half of candidates as not eligible for statin therapy.

Identifying Individuals at Risk for Cardiovascular Events Across the Spectrum of Blood Pressure Levels.

BackgroundWe determined the proportion of atherosclerotic cardiovascular disease (ASCVD) events that occur across the spectrum of systolic blood pressure (SBP) and assessed whether multivariable risk assessment can identify persons who experience ASCVD events at all levels of SBP, including those with goal levels.Methods and ResultsParticipants aged 45 to 64 years from the Framingham Offspring and Atherosclerosis Risk in Communities studies were stratified based on treated and untreated SBP levels (<120, 120 to 129, 130 to 139, 140 to 149, 150 to 159, ≥160 mm Hg). We determined the number of excess ASCVD events in each SBP stratum by calculating the difference between observed and expected events (ASCVD event rate in untreated SBP <120 mm Hg was used as the reference). We categorized participants into 10-year ASCVD risk groups using the Pooled Cohort risk equations. There were 18 898 participants (78% white; 22% black) who were followed for 10 years. We estimated 427 excess ASCVD events, of which 56% (109 of 197) and 50% (115 of 230), respectively, occurred among untreated and treated participants with elevated SBP who were not recommended for antihypertensive therapy. Among untreated participants, 10-year ASCVD risk ≥7.5% identified 64% of those who experienced an ASCVD at 10 years and 30% of those who did not. Multivariable risk assessment was less useful in baseline-treated participants.ConclusionsHalf of excess ASCVD events occurred in persons with elevated SBP who were not currently recommended for antihypertensive therapy. Multivariable risk assessment may help identify those likely to benefit from further risk-reducing therapies. These findings support consideration of multivariable risk in guiding prevention across the spectrum of SBP.

Utility of Nontraditional Risk Markers in Individuals Ineligible for Statin Therapy According to the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines

In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors. Whether use of nontraditional risk markers can improve risk assessment in those below this threshold for statin therapy is unclear. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline, we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke. Adults with an initial cPCE <7.5% and elevated levels of additional risk markers (abnormal test) whose new calculated risk was ≥7.5% were considered statin eligible: low-density lipoprotein cholesterol ≥160 mg/dL; family history of ASCVD; high-sensitivity C-reactive protein ≥2 mg/dL; coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity; and ankle-brachial index <0.9. We compared the absolute and relative ASCVD risks among those with versus without elevated posttest estimated risk. We calculated the number needed to screen to identify 1 person with abnormal test for each risk marker, defined as the number of participants with baseline cPCE risk <7.5% divided by the number with an abnormal test reclassified as statin eligible. Of 5185 participants not taking statins with complete data (age, 45-84 years), 4185 had a cPCE risk <7.5%. During 10 years of follow-up, 57% of the ASCVD events (183 of 320) occurred among adults with a cPCE risk <7.5%. When people with diabetes mellitus were excluded, the coronary artery calcium criterion reclassified 6.8% upward, with an event rate of 13.3%, absolute risk of 10%, relative risk of 4.0 (95% confidence interval [CI], 2.8-5.7), and number needed to screen of 14.7. The corresponding numbers for family history of ASCVD were 4.6%, 15.1%, 12%, 4.3 (95% CI, 3.0-6.4), and 21.8; for high-sensitivity C-reactive protein criteria, 2.6%, 10%, 6%, 2.6 (95% CI, 1.4-4.8), and 39.2; for ankle-brachial index criteria, 0.6%, 9%, 5%, 2.3 (95% CI, 0.6-8.6), and 176.5; and for low-density lipoprotein cholesterol criteria, 0.5%, 5%, 1%, 1.2 (95% CI, 0.2-8.4), and 193.3, respectively. Of the 3882 with <7.5% cPCE risk, 431 (11.1%) were reclassified to ≥7.5% (statin eligible) by at least 1 of the additional risk marker criteria. In this generally low-risk population sample, a large proportion of ASCVD events occurred among adults with a 10-year cPCE risk <7.5%. We found that the coronary artery calcium score, high-sensitivity C-reactive protein, family history of ASCVD, and ankle-brachial index recommendations by the American College of Cardiology/American Heart Association cholesterol guidelines (Class IIB) identify small subgroups of asymptomatic population with a 10-year cPCE risk <7.5% but with observed ASCVD event rates >7.5% who may warrant statin therapy considerations.