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Corresponding author at: Center for Human Nutrition of the University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390
Departments of Internal MedicineCenter for Human Nutrition of the University of Texas Southwestern Medical Center at Dallas, United Statesthe Veterans Affairs North Texas Healthcare System, Dallas, TX, United States
Clinical NutritionCenter for Human Nutrition of the University of Texas Southwestern Medical Center at Dallas, United Statesthe Veterans Affairs North Texas Healthcare System, Dallas, TX, United States
Statins reduce atherosclerotic cardiovascular disease in women and men.
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Women develop coronary atherosclerosis more slowly than men.
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About 25% of women are statin eligible, as implied by coronary artery calcium.
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In most women, CAC should guide treatment decisions.
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In high-risk women (e.g. severe hypercholesterolemia), CAC scoring is optional.
By current guidelines, statin treatment decisions depend on multiple risk factor algorithms (e.g., pooled cohort equations [PCEs]). By available PCEs most older middle-aged women are statin eligible. But several studies cast doubt on reliability of available PCEs for ASCVD risk assessment. An alternative method for risk assessment is a coronary artery calcium (CAC) score. Many older women have zero CAC, which equates to low risk for ASCVD; these women can delay statin therapy for several years before re-scanning. When CAC is 1-99 Agatston units, risk is only borderline high and statin delay also is an option until re-scanning. When CAC is > 100 Agatston units, risk is high enough to warrant a statin. In most women, CAC is the best guide to treatment decisions. In high-risk women (e.g., diabetes and severe hypercholesterolemia), generally are indicated, but CAC can assist in risk assessment, but other risk factors also can aid in treatment decisions.
Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel.
in turn, these receptors remove LDL-C from the circulation.
In patients with ASCVD, randomized controlled trials (RCTs) demonstrate that statins reduce recurrent cardiovascular events by 25–50% and total mortality by about 10–15%.
Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
Cholesterol Treatment Trialists' (CTT) Collaboration Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials.
The strongest evidence exists in patients with established ASCVD (secondary prevention). Here, there is a widespread consensus that statins should be based on absolute risk and used similarly in men and women.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
In principle, the same holds for primary prevention; however, in women, atherosclerosis develops more slowly than in men; and as a result, onset of ASCVD is delayed in women by at least a decade. This delay has important clinical implications for statin therapy in women.
Statin eligibility
Current guidelines for primary prevention with statin therapy are based mainly on benefit in ASCVD morbidity, as observed in RCTs.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
Treatment recommendations assume that reduction in major ASCVD events will ultimately reduce total mortality. But even when life is not extended by statin therapy, living a life free of clinical ASCVD or one in which onset of ASCVD is delayed is defensible by many specialists.
According to 2013 American Heart Association/American College of Cardiology advice,
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
evidence-based review of RCTs establishes that statin therapy safely reduces hard ASCVD (i.e., myocardial infarction, stroke, and peripheral arterial disease) when 10-year risk is > 7.5%. RCTs further showed that statin therapy is largely safe and cost-effective. A risk of > 7.5% therefore defined the threshold for statin eligibility. This threshold was re-affirmed by 2018 cholesterol guidelines;
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
and it is widely embraced by the cardiovascular community. At this threshold, the number needed to treat (NNT) to prevent one ASCVD event in 10 years with a moderate-intensity statin is approximately 40. Accepting such a high 10-year NNT is justified by the assumption that over a lifetime of statin therapy, the NNT will be much lower.
It is likely that statin therapy will reduce risk in populations having risk levels below a 10-year risk of 7.5%.
At a lower risk, the NNT would be higher and cost effectiveness lower. Setting a statin therapy threshold at 7.5%, therefore, seems a reasonable threshold for routine clinical practice.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
emphasize the clinician-patient risk discussion, a dialogue about potential net benefit of lifestyle intervention and cholesterol-lowering drugs (especially statins). The discussion covers risk reduction efficiency, drug side effects, drug-drug interactions, and patient preferences. The patient discussion should reach a clinical judgment as to net benefit of statin therapy and to evaluate patient agreement and motivation for long-term treatment. Periodic monitoring is required to confirm treatment efficacy and adherence to therapy.
Estimating absolute 10-year risk
The first step in estimating net benefit is to estimate 10-year risk for ASCVD. This interval is more reliable than predictions of lifetime outcomes. The 10-year estimate typically employs a set of major risk factors. The Framingham Heart Study was first used to apply prospective population data to assess risk for individuals.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines.
these equations are specific for gender and ethnicity. Risk factors consist of age, blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and presence or absence of cigarette smoking and diabetes. In Figure 1, the distributions of categories of PCE-estimated risk in women of the NHANES population are shown by decade. Three ranges of 10-year risk for ASCVD are defined by treatment guidelines
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
: low (< 7.5%), intermediate (7.5-< 20.0%), and high (>20%). According to these guidelines, patients at low risk generally are not statin eligible; those at intermediate risk are candidates for moderate intensity statins; and high-risk patients benefit most from high-intensity statins.
Figure 1Distribution of categories of PCE-estimated risk in women of the NHANES population are shown by decade. Three ranges of 10-year risk for ASCVD are defined: low (< 7.5%), intermediate (7.5–19.9%), and high (>20%). According to treatment guidelines, patients at low risk generally are not statin eligible; those at intermediate risk are candidates for moderate intensity statins; and high-risk patients benefit most from high-intensity statins.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the american heart association and american college of cardiology.
PCEs tended to overestimate the actual risk observed in healthier cohorts. Overestimation of risk was particularly common near the threshold for statin eligibility. Thus, in healthier cohorts, a PCE-estimated risk of >7.5% could overestimate statin eligibility. One reason for overestimating risk by PCEs may be a decline in population baseline risk since that of earlier cohorts used in the development of PCEs.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines.
Beyond this, applying population-acquired risk algorithms to individuals carries inaccuracies due to variation in atherosclerosis burden in a given risk category. What is needed is a more precise individualization in risk assessment.
Over the past two decades, the Multiethnic Study of Atherosclerosis
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
Heinz Nixdorf recall study investigators. Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study.
Heinz Nixdorf recall study investigators. Value of progression of coronary artery calcification for risk prediction of coronary and cardiovascular events: result of the HNR study (Heinz Nixdorf Recall).
Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.
it also provides patient-specific predictions. This personalization of risk differs from PCEs, which only apply average population risk to individuals.
MESA has identified three major categories of CAC scores that correlate with ASCVD risk.
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
The distribution of patients with zero CAC generally has a low 10-year risk for vascular events (<5%). Most patients with CAC 1-99 Agatston units are generally in the range of borderline 10-year risk by PCEs (5-<7.5%). A CAC score > 100 Agatston units is typically accompanied by 10-year risk > 7.5%,
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
The higher the CAC score, the greater is the risk. This is in accord with recently published National Lipid Association (NLA) recommendations for use of CAC scoring in patients with different categories of CHD.
found that CAC scores are not identically related to ASCVD risk between women and men. For a given CAC score, women appear to have a somewhat higher risk than men. To the present time, however, this difference has not been shown to modify the risk categories between women and men.
Over the past decade, expert panels have given increased attention to the use of CAC as guide to statin therapy.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the american heart association and american college of cardiology.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines.
CAC is identified as advanced risk assessment for selected individuals, i.e., those with 10-year risk >7.5% by PCEs but in whom accuracies of risk estimates are questioned.
Clinical implications of CAC scoring for women
Zero CAC
In the MESA cohort, approximately half of women ages 65–74 have zero CAC (Figure 2).
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort.
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
thus, in women with PCE-estimated risk > 7.5% but zero CAC, statin therapy seems unnecessary for up to a decade before CAC rescanning. Our conclusion is based on the observation that only 8% of women develop a CAC score > 100 Agaston units over 10 years.
have introduced the concept of warranty period for likely conversion to CAC score greater than zero to define an acceptable time limit before rescanning in a zero-CAC score patient at intermediate risk by PCE analysis. These investigators propose a warranty period of 3–7 years (average 5 years), i.e, a proposed interval for re-scanning. This interval is endorsed by the NLA guidelines.
2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: a report of the society of cardiovascular computed tomography and society of thoracic radiology.
favor statin therapy in this risk range; it must be noted that treatment of borderline risk with a moderate-intensity statin carries a relatively high NNT, compared to the risk threshold of > 7.5% proposed in AHA/ACC guidelines.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
Figure 2Distribution of CAC score categories in women reported for the MESA study. The CAC score ranges are zero, 1-100 and > 100 Agaston units. (copyright reference 25).
Whether to rescan women > 75 years old who previously had zero CAC is uncertain. RCT data on statin therapy in patients >75 years are limited but are suggestive of statin benefit.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
recommend that CAC scanning be considered mainly for patients at intermediate risk (10-year risk 7.5 - <20% as determined by PCEs). Although CAC could be used for routine risk assessment in all women > 55 years, the yield in positive findings would be considerably reduced. The prevalence of zero CAC in MESA patients at intermediate risk range between 35 and 55%, depending on PCE score.
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort.
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort.
this percentage is even lower at ages 55–64 years. In addition, a portion of women with zero CAC will have converted to CAC scores of 1-99 Agatston units on re-scanning. In both groups, when the CAC score is 1-99 Agatston units and 10-year risk by PCEs is 7.5-15%, some coronary atherosclerosis is present and ASCVD events occur in the range of 5-<7.5% per decade (borderline risk).
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).
J Am Coll Cardiol.2015 Oct 13; 66 (Erratum in: J Am Coll Cardiol. Dec 15;66(23):2686. Miemdema, Michael D [corrected to Miedema, Michael D]): 1657-1668https://doi.org/10.1016/j.jacc.2015.07.066
Again, this range is below categorical statin eligibility. Despite a relatively high NNT, statin therapy is an option based on the clinician patient risk discussion;
but alternatively, therapy can be delayed before re-scanning. A warranty period for this category has not been studied; presumably, the higher the baseline score, the shorter should be the period. When patients with CAC scores 1-99 Agatston units and 10-year risk by PCE is > 15%, actual 10 year risk is >7.5% and immediate initiation of statin therapy is warranted.
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).
J Am Coll Cardiol.2015 Oct 13; 66 (Erratum in: J Am Coll Cardiol. Dec 15;66(23):2686. Miemdema, Michael D [corrected to Miedema, Michael D]): 1657-1668https://doi.org/10.1016/j.jacc.2015.07.066
When statin therapy is delayed, especially in those 55–64 years, repeat CAC after 10 years is prudent to detect advancing atherosclerosis i.e., CAC > 100 Agatston units and statin eligibility.
CAC > 100 Agatston units
When CAC score is > 100 Agatston units and 10-year risk by PCEs is > 7.5%, a 10-year risk of > 7.5% is confirmed;
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
10-year NNT will be <40. About 25% of women ages 65–74 years will be statin eligible. Even fewer will be statin eligible in the age range 55–64 years (Figure 2).
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort.
The goal is to lower LDL-C by > 50%, which can be obtained by a high-intensity statin or by combining a moderate-intensity statin with a nonstatin e.g., ezetimibe or bile acid sequestrant.
Combined therapy including a moderate-intensity statin may be better tolerated than a high-intensity statin but with the same LDL-lowering.
MESA findings reveal why statin therapy in women often fails to show significant benefit in primary- prevention RCTs. At most, only about one-fourth of women are at high enough risk to demonstrate a significant risk benefit in a 5-year statin RCT.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
list several conditions as being categorically high risk and are statin eligible without further risk assessment. The following discusses whether to modify this position based on CAC scanning.
Diabetes
Statin therapy is advocated for most adults with diabetes– both men and women.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report.
Sex differences in all-cause and cardiovascular mortality, hospitalization for individuals with and without diabetes, and patients with diabetes diagnosed early and late.
Coronary artery calcium score for long-term risk classification in individuals with Type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis.
Coronary artery calcium score for long-term risk classification in individuals with Type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis.
It can be argued that this level of risk justifies statin therapy in most patients with diabetes but zero CAC. Yet, such patients are heterogeneous and the decision when to initiate a statin in a woman depends on careful review of all risk considerations in the clinician-patient risk discussion. In those judged to be at lower risk, a statin can be withheld with rescanning at 5 years.
In about 10% of patients treated with statins, the fasting glucose rises to the level of categorical diabetes.
This response has been of concern to both clinicians and patients. But the risk/benefit ratio strongly favors statin therapy in patients at significant risk for ASCVD.
Coronary artery calcium score for long-term risk classification in individuals with Type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
however, showed that many individuals with very high LDL-C levels have zero or low CAC scores and low 10-year risk of ASCVD. In asymptomatic women with LDL-C > 190 mg/dL, CAC scanning before statin initiation is reasonable. If CAC is zero, referral to a lipid specialist may be prudent. Sooner or later, most patients with severe hypercholesterolemia will require a statin. If a statin is withheld because of zero CAC, rescanning every five years is justified.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
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).
J Am Coll Cardiol.2015 Oct 13; 66 (Erratum in: J Am Coll Cardiol. Dec 15;66(23):2686. Miemdema, Michael D [corrected to Miedema, Michael D]): 1657-1668https://doi.org/10.1016/j.jacc.2015.07.066
found that 26% of patients in the MESA cohort who were in the high-risk range by PCE had zero CAC and low rates of ASCVD. They suggest that immediate statin therapy is optional in this subgroup. Re-scanning after 5 years is reasonable. Moreover, in 28% of subjects, CAC ranged from 1-99 Agatston units, which implies a 10-year risk of <7.5%; this makes statin therapy optional for up to 5 years before re-scanning.
are insufficient to determine whether zero CAC has the power to delay the use of statin therapy in cigarette smokers with PCE-estimated risk of > 7.5%. The available data suggest that PCEs adequately stratify 10-year risk in smokers. In other words, a PCE-estimated risk of > 7.5% in a smoker can be called statin eligible. Furthermore, CAC scanning is not necessary.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
proposed that several risk enhancing factors raise risk for ASCVD above the standard risk factors of PCEs. In other words, in patients at intermediate risk, risk enhancing factors should favor use of statins. To compare risk enhancing factors to CAC for risk assessment, in MESA, Patel et al.
Assessment of coronary artery calcium scoring to guide statin therapy allocation according to risk-enhancing factors: the multi-ethnic study of atherosclerosis.
examined whether in patients with CAC scores of 0, risk-enhancing factors are associated with ASCVD risk as well as or better than CAC The results favored CAC scoring over risk-enhancing factor in a decision for statin therapy. However more studies are needed for a final determination of the utility of risk enhancing factors.
Statin compliance in women
The literature suggests that women are less compliant to statin therapy than are men.
summarize available strategies for improvement of drug adherence. Perhaps the single greatest factor preventing successful statin treatment is longtime maintenance of drug adherence. This challenge exists for all pharmacological therapies that require persistent drug adherence for cardiovascular prevention.
Multifactorial cardiovascular risk in women
Cardiovascular disease continues to be the major cause of morbidity and mortality among US women.
Much of this is atherosclerotic in origin. In women, stroke accounts for a greater proportion of cardiovascular events than in men; and average of onset of disease is about a decade later in women compared to men.
All the major risk factors (cigarette smoking, hypertension, diabetes, metabolic syndrome, and dyslipidemia) contribute to atherosclerosis, but also mediate cardiovascular disease through other mechanisms. Treatment of all the major risk factors is necessary to maximize risk reduction. In women with multiple risk factors, CAC scoring can help to identify those who will benefit from statin therapy.
There is growing evidence that characteristics of atherosclerotic plaques differ between men and women.
It is possible, although not proven, that CAC scores in Agatston units do not predict risk equally in men and women. But available evidence suggests that differences in prediction occur primarily when Agatston scores are >100 units.
Conclusions
This document argues that for primary prevention in women at intermediate risk, according to PCEs, CAC scanning should be carried out in most before starting statin therapy. The basic concept is that the CAC score is a more reliable indicator of statin eligibility than is PCE-estimated risk.
In most women with PCE-estimated intermediate risk, those with zero CAC have a low 10-year risk; thus, statin treatment can be delayed for up to 10 years before CAC re-scanning. When CAC is 1-99 Agatston units, risk is borderline high and delaying a statin for a lesser period before re-scanning is a reasonable option. But when CAC > 100 Agatston units, 10-year risk is > 7.5%, and statin therapy is indicated. In women with categorically high-risk conditions i.e., diabetes, severe hypercholesterolemia, and a PCE-estimated 10-year risk > 20%, treatment with a statin is generally recommended.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
However, measurement of CAC in these women seems appropriate. In “high-risk” women with zero CAC, it is reasonable to delay statin therapy for about 5 years before re-scanning; when CAC equals 1-99 Agatston units in these women, direct initiation of a statin is reasonable. Overall, if CAC measurements are carried out in women at apparent risk before starting a statin, a sizable portion will have zero CAC and treatment can be delayed until significant CAC develops.
Contributions
All authors have made substantial contributions to all of the following:
Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel.
The authors thank Dr. Jijia Wang, Department of Applied Clinical Sciences, UT Southwestern School of Health Professions for consultation on data provided in Figure 1.
Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel.
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American college of cardiology/American heart association task force on practice guidelines.
J Am Coll Cardiol.2014 Jul 1; 63 (Epub 2013 Nov 12. Erratum in: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):3024-3025. Erratum in: J Am Coll Cardiol. 2015 Dec 22;66(24):2812): 2889-2934https://doi.org/10.1016/j.jacc.2013.11.002
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines.
2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American college of cardiology/American heart association task force on practice guidelines.
Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the american heart association and american college of cardiology.
Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA).
Heinz Nixdorf recall study investigators. Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study.
Heinz Nixdorf recall study investigators. Value of progression of coronary artery calcification for risk prediction of coronary and cardiovascular events: result of the HNR study (Heinz Nixdorf Recall).
Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis.
Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort.
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J Am Coll Cardiol.2015 Oct 13; 66 (Erratum in: J Am Coll Cardiol. Dec 15;66(23):2686. Miemdema, Michael D [corrected to Miedema, Michael D]): 1657-1668https://doi.org/10.1016/j.jacc.2015.07.066
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report.
Sex differences in all-cause and cardiovascular mortality, hospitalization for individuals with and without diabetes, and patients with diabetes diagnosed early and late.
Coronary artery calcium score for long-term risk classification in individuals with Type 2 diabetes and metabolic syndrome from the multi-ethnic study of atherosclerosis.
Assessment of coronary artery calcium scoring to guide statin therapy allocation according to risk-enhancing factors: the multi-ethnic study of atherosclerosis.
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