Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease

Navar-Boggan, Ann Marie; Peterson, Eric D.; D’Agostino, Ralph B.; Neely, Benjamin; Sniderman, Allan D.; Pencina, Michael J.

doi:10.1161/circulationaha.114.012477

Cited by 322 publications

(220 citation statements)

References 16 publications

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“…Our results in HeFH with an established genetic diagnosis reinforce the concept of an association between early, lifelong cholesterol exposure and premature atherosclerosis shown in non-HeFH subjects of the Framingham offsprings cohort (22). Here, in HeFH subjects, we showed an independent association between TCB and calcified coronary atherosclerotic burden that expands previous results on arterial stiffening and thickening (23).…”

supporting

confidence: 89%

Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia

Gallo

Giral

Carrié

et al. 2017

Journal of Clinical Lipidology

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supporting

confidence: 89%

Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia

Gallo

Giral

Carrié

et al. 2017

Journal of Clinical Lipidology

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“…Individualized statin benefit provides an evidence-based approach to extending eligibility to younger, lower-risk individuals by identifying even in the short term the benefits of controlling moderate elevations in LDL and fills an important gap in the management of such patients. [29][30][31] This approach is consistent with mounting evidence from lifetime risk estimates, 32 mendelian randomization, 33 and recent observational studies, 34 as well as RCT data, 9 demonstrating that LDL control in early to middle adulthood, rather than later in life, may be more effective in preventing cardiovascular disease. Our approach differs markedly from other approaches for personalized prevention, which focus uniquely on improved stratification of predicted risk with little or no attention to the clinical benefits of therapy.…”

Section: Downloaded Fromsupporting

confidence: 73%

Individualized Statin Benefit for Determining Statin Eligibility in the Primary Prevention of Cardiovascular Disease

et al. 2016

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Association (ACC/AHA) cholesterol guidelines determined that except for those with diabetes mellitus or low-density lipoprotein (LDL) cholesterol (LDL-C) >190 mg/dL, individuals should be selected for statin therapy for primary prevention of cardiovascular disease on the basis of predicted 10-year cardiovascular risk.1 Such a risk-based approach leads to greater statin eligibility among older individuals with lower levels of LDL-C while limiting eligibility in younger individuals with higher LDL-C because predicted risk is driven primarily by age.2 Defining statin eligibility with the use of a predicted risk threshold also implicitly assumes that the benefit of statins is constant in all eligible individuals, regardless of the factors that contribute to their increased risk such as higher age as opposed to higher LDL-C.Alternative approaches in determining statin eligibility have also been proposed recently, including the use of novel markers for better risk classification 3,4 and the use of entry criteria for randomized, controlled trials (RCTs) to define statin benefit groups. 5,6 Moreover, Pandya et al 7 have shown that statin preventive therapy remains cost-effective even at lower risk thresholds than selected by the ACC/AHA guidelines. Although each of these approaches has advantages and disadvantages, none directly considers the clinical benefits from statin therapy for each individual on the basis of the available clinical trial data. We compared statin eligibilities using 2 separate approaches: a 10-year risk-based approach (≥7.5% 10-year risk) and an individualized benefit approach (ie, based on predicted absolute risk reduction over 10 years [ARR 10 ] ≥2.3% from randomized, controlled trial data). A risk-based approach led to the eligibility of 15.0 million (95% confidence interval, 12.7-17.3 million) Americans, whereas a benefit-based approach identified 24.6 million (95% confidence interval, 21.0-28.1 million). The corresponding numbers needed to treat over 10 years were 21 (range, 9-44) and 25 (range, 9-44). The benefit-based approach identified 9.5 million lower-risk (<7.5% 10-year risk) Americans not currently eligible for statin treatment who had the same or greater expected benefit from statins (≥2.3% ARR 10 ) compared with higher-risk individuals. This lower-risk/acceptable-benefit group includes younger individuals (mean age, 55.2 versus 62.5 years; P<0.001 for benefit based versus risk based) with higher low-density lipoprotein cholesterol (140 versus133 mg/dL; P=0.01). Statin treatment in this group would be expected to prevent an additional 266 508 cardiovascular events over 10 years. Conclusions-An individualized statin benefit approach can identify lower-risk individuals who have equal or greater expected benefit from statins in primary prevention compared with higher-risk individuals. This approach may help develop guideline recommendations that better identify individuals who meaningfully benefit from statin therapy.

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“…The report by Navar-Boggan and colleagues 1 that cumulative exposure to elevated non-high-density lipoprotein (HDL) cholesterol is a strong independent risk factor for cardiovascular (CV) risk is a highly important finding, one that, if confirmed, provides strong evidence in support of previous genetic studies. 2 However, the suggestion that their results call into question a cardiovascular risk-based approach such as that proposed in the new American College of Cardiology/American Heart Association guidelines is in error.…”

Section: To the Editormentioning

confidence: 86%

Letter by Hayward Regarding Article, “Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease”

Hayward

2015

Circulation

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1 that cumulative exposure to elevated non-high-density lipoprotein (HDL) cholesterol is a strong independent risk factor for cardiovascular (CV) risk is a highly important finding, one that, if confirmed, provides strong evidence in support of previous genetic studies. 2 However, the suggestion that their results call into question a cardiovascular risk-based approach such as that proposed in the new American College of Cardiology/American Heart Association guidelines is in error. Their study simply suggests that we can better estimate our patient's cardiovascular risk if we can accurately assess their cumulative non-HDL cholesterol in real-world clinical practice. The authors could help make their findings clinically actionable by conducting reliability analyses on their data (Do we need 3 measures over 5 years or annual measures over a decade to reliability estimate a patient's cumulative non-HDL cholesterol?). This information, combined with the associated hazard ratio for how this increases or decreases a patient's estimated cardiovascular risk obtained by current risk calculators, would be a major advance in guideline primary cardiovascular prevention, not just for lipid therapies. 3-5However, it is the relative impact of any risk factor that is important, not the average risk of all people with that risk factor. 3Even if being in the top cumulative non-HDL cholesterol risk category doubles the estimated atherosclerotic cardiovascular disease risk score on average, this is still not important for the 55-year-old woman with a 10-year atherosclerotic cardiovascular disease risk estimate of 1% (her 10-year risk is still only ≈2%).4 By concentrating on the average risk of all those 55 years of age with an elevated non-HDL cholesterol, the authors averaged the cardiovascular risk of the above woman with someone whose risk doubled from 20% to 40%, and mean results are highly susceptible to extreme values. The authors' findings do not provide any evidence against statin treatment being primarily guided by the best estimate of a person's overall cardiovascular risk; they only provide evidence that we can estimate cardiovascular risk better. However, finding heterogeneity in the relative risk reduction (RRR) of statin in a patient's cumulative non-HDL cholesterol, which was not examined in the authors' study, would challenge the American College of Cardiology/American Heart Association risk-based approach. 4,5 Although all currently available clinical trial evidence suggests that the RRR of a statin does not vary by a person's baseline low-density lipoprotein level (ie, RRR is the same whether LDL is 200 or 100 mg/dL), if the RRR of a statin is greater in those with higher versus lower cumulative non-HDL cholesterol, that would necessitate a change to a full benefit-based tailored treatment approach in which both overall cardiovascular risk and heterogeneity in the RRR of the treatment must be considered.

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Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease

Cited by 322 publications

References 16 publications

Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia

Early coronary calcifications are related to cholesterol burden in heterozygous familial hypercholesterolemia

Individualized Statin Benefit for Determining Statin Eligibility in the Primary Prevention of Cardiovascular Disease

Letter by Hayward Regarding Article, “Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease”

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