Elevated 'Lipid-Years' in Young Adulthood Tied to Later CHD

Marlene Busko

January 26, 2015

DURHAM, NC — Fifty-five-year-olds who had prolonged moderately elevated non–HDL-cholesterol levels (>160 mg/dL) when they were young adults were much more likely than their peers to have coronary heart disease by the time they were 70, in an analysis based on the Framingham Offspring Cohort[1]. The risk of CHD (defined as MI, angina, coronary insufficiency, or death from CHD) increased with exposure to elevated lipids in a dose-dependent way, according to the study published published online January 26, 2015 in Circulation.

Specifically, during follow-up, 16.5% of the middle-aged adults who had hyperlipidemia in the past 11 to 20 years developed CHD, but only 8.1% of those with hyperlipidemia in the past 1 to 10 years developed CHD. Among the adults without past hyperlipidemia, only 4.4% developed CHD.

Having decades of exposure to what many would consider to be mild to moderately elevated cholesterol level is associated with a significantly elevated risk of cardiovascular disease, Dr Ann Navar-Boggan (Duke University Medical Center, Durham, NC) told heartwire . Thus, "the way we think about smoking in terms of pack-years, we should be thinking about 'lipid-years' [of exposure to high cholesterol]."

For young adults, "we really need to remember that the foundation for cardiovascular disease is being laid in our 20s, 30s, and 40s, [and] risk-factor modification at that age may be really important," she said.

For middle-aged adults, "in the same way that a 55-year-old with a family history of cardiovascular disease [or] an increased coronary calcium score would be considered higher risk, we should take into consideration the duration of exposure to high blood cholesterol . . . to stratify risk."

Decades of High Cholesterol: A New CHD Risk Factor?

Atherosclerosis develops slowly over many years, and the effects of prolonged exposure to elevated cholesterol in young adulthood aren't well defined, Navar-Boggan explained.

The group examined data from 1478 individuals in the offspring cohort of the Framingham Heart Study who were approximately 55 years old and did not have a history of CVD when they were enrolled during 1987 to 1998.

Participants were stratified into three groups based on hyperlipidemia (non–HDL cholesterol >160 mg/dL) at enrollment. A total of 512 participants had no hyperlipidemia; 389 participants had 1 to 10 years of hyperlipidemia; and 577 had 11 to 20 years of hyperlipidemia.

Only 85 participants (5.8%) were on lipid-lowering treatment at baseline.

During a median follow-up of 15 years, there were 136 CHD events. The unadjusted risk of CHD doubled for every 10 years of exposure to hyperlipidemia during age 35 to 55 (HR 2.0, 95% CI 1.63–2.45 per decade of hyperlipidemia).

The association was attenuated but remained statistically significant after adjustment for sex, age, systolic blood pressure, antihypertensive therapy, smoking status, HDL cholesterol, diabetes, and non–HDL cholesterol at baseline (adjusted HR 1.39, 95% CI 1.05–1.85 per decade of hyperlipidemia). The association also remained significant after adjustment for lipid-lowering–therapy use at baseline and follow-up.

Based on the 2013 ACC/AHA Cholesterol Guidelines (using the 10-year CVD risk threshold of >7.5%), among the 55-year-old adults who had been exposed to high cholesterol for 11 to 20 years, 15.1% would have met the criteria for statin therapy at age 40 and 34.8% would have met criteria at age 50. However, this study was not designed to determine whether early statin intervention in young adults "on the hyperlipidemic trajectory" would decrease future CHD risk, the researchers write.

Also, "we don't have longer-term safety and efficacy data using statins starting at an earlier age, such as in the 30s and 40s, so guidelines, doctors, and the AHA would all agree that the best way for controlling high cholesterol particularly for young adults is with diet and exercise and not with medication as the first-line [treatment]," Navar-Boggan said.

However, "it's certainly not a stretch to say that at least adults in their 50s who have had long-term exposure to high cholesterol should be considered for statin therapy, and there are [randomized clinical trial] data to support the efficacy in that group."

This study used non–HDL-cholesterol cut-offs, since HDL was measured directly whereas LDL was calculated. Typically, non–HDL cholesterol is 30 mg/dL higher than LDL cholesterol, and the researchers found similar results using an LDL-cholesterol level of >130 mg/dL.

Individuals who had average non–HDL-cholesterol levels levels during the preceding 20 years that were below 125 mg/dL had a similar low risk of CHD, and those with levels above 195 mg/dL had a similar high risk of CHD. For every 10-point increase in non–HDL cholesterol between 125 and 195 mg/dL, there was a 33% increased risk of CHD.

"I think the jury's still out . . . for what we should consider 'normal' cholesterol . . . both for primary and secondary prevention," Navar-Boggan said.

Nevertheless, this study identifies adults who may benefit from more aggressive primary prevention, the researchers conclude. "Our findings suggest that adults with longstanding moderate elevations in non–HDL-cholesterol levels should be added to those already identified by the current guidelines as candidates for an informed patient-physician discussion about appropriate lipid-management strategies to reduce future risk of heart disease."

This study was supported by the Duke Clinical Research Institute and the Agency for Healthcare Research and Quality. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University. Navar-Boggan has no relevant financial relationships; disclosures for the coauthors are listed in the article.

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