Fifty-three year follow-up of coronary heart disease versus HDL2 and other lipoproteins in Gofman's Livermore Cohort

Abstract

This article is available online at http://www.jlr.org concentrations that were 32% lower for HDL2 and 8% lower for HDL3 (the less buoyant particles) compared with those who did not develop CHD ( 3 ).Gofman's initial observation gave rise to studies by others on the potential clinical utility of HDL2 and HDL3 measurements. Rather than employing Gofman's original methodology, they measured HDL2-and HDL3-cholesterol by precipitation and HDL size classes by nuclear magnetic resonance (NMR) or, more rarely, ultracentrifugation. Many studies showed that high HDL2 was associated with lower CHD risk ( 4-10 ); however, the independent effects of HDL2 and HDL3 on CHD risk remained inconclusive ( 5, 7-10 ). Currently, the National Cholesterol Education Program Adult Treatment Panel (ATP-III) guidelines ( 11 ) state that "although small studies suggest greater predictive power of one or another HDL component, their superiority over HDL-cholesterol has not been demonstrated in large, prospective studies. Consequently, ATP III does not recommend the routine measurement of HDL subspecies in CHD risk assessment." However, the clinical utility of HDL subclasses may be underappreciated in part due to the limitations of these alternative methods to adequately characterize HDL heterogeneity ( 12-16 ).Between 1954 and 1956, John Gofman created a cohort of 1,905 men in whom lipoproteins were measured by analytic ultracentrifugation ( 3 ). Our rediscovery of Gofman's original data enabled us to assess the relationships of lipoprotein mass concentrations to CHD during 29-year follow-up ( 17 ). Those analyses showed that i ) the lowest quartile of HDL2-mass increased the men's risks of fatal plus nonfatal CHD by 38% and their risks of premature CHD (age р 65 years) by 61% when adjusted for traditional risk factors, ii ) the HDL2-CHD risk relationship remained signifi cant when adjusted for HDL3, and iii ) the risk reduction per mg/dl of HDL-mass was signifi cantly greater Abstract To assess the relationships of lipoprotein mass concentrations to all-cause and coronary heart disease (CHD) mortality, we analyzed the prospective 53-year follow-up of 1,905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Cause of death was determined from medical records and death certifi cates before 1979 and from National Death Index death diagnoses thereafter. Of the 1,329 men (69.8%) who died through 2008 , CHD was listed as a contributing cause of death for 409 men, including 113 deaths from premature CHD (age р 65 years). When adjusted for age, the risk associated with the lowest HDL2 quartile increased 22% for all-cause ( P = 0.001), 63% for total CHD ( P < 10 ؊ 5 ), and 117% for premature CHD mortality ( P = 0.0001). When adjusted for standard risk factors (age, total cholesterol, blood pressure, BMI, smoking) and the lowest HDL3 quartile, the corresponding risk increases were 14% ( P = 0.05), 38% ( P = 0.004), and 62% ( P = 0.02), respectively. Men with HDL3 р 25 th percentile had 28% greater ...

Low High‐Density Lipoprotein 3 Reduces the Odds of Men Surviving to Age 85 During 53‐Year Follow‐Up

“…LDL mass concentrations only weakly affected survival until 85, in contrast to the strong association reported previously between LDL and total and premature CHD . In the current study, the significant inverse relationship between LDL mass and the odds of surviving until 85 became nonsignificant when adjusted for other risk factors, notably cigarettes/day smoked (adjusted P = .15), systolic blood pressure (adjusted P = .06), and total cholesterol (adjusted P = .14), the last having strong colinearity with LDL mass concentrations (correlated r = 0.75 at baseline).…”

“…HDLs may be separated into two major subfractions: larger, more‐buoyant HDL2 particles (1.063–1.125 g/mL) and smaller, less‐buoyant HDL3 particles (1.125–1.210 g/mL) . Recently, using a direct measurement of total mass, it was reported that the lowest quartiles of HDL2 and HDL3 were associated prospectively with greater risk of CHD …”

“…This article examines whether the mass concentrations of HDL2, HDL3, and other lipoproteins measured directly using analytic ultracentrifugation predict the odds of men surviving until the age of 85 in John Gofman's prospective study of employees at Lawrence Livermore National Laboratory (formerly Livermore Radiation Laboratory) . The analyses are unique in that they involve the oldest existing cohort in which HDL2 and HDL3 were measured directly and participants were followed prospectively . In addition, serum concentrations of low‐density lipoprotein (LDL), intermediate‐density lipoprotein (IDL), and small and large very low‐density lipoprotein (VLDL) mass were measured directly rather than their usual approximation from estimated LDL‐C and VLDL‐C .…”

High-Density Lipoprotein Particle Subclass Heterogeneity and Incident Coronary Heart Disease

“…2, 10, 25 Prior studies that evaluated HDL size using these other subfractionation methods have mostly found inverse association for large HDL size with CHD but equivocal results for smaller HDL size. 26–34 …”

Interaction between HDL and inflammation: When the good turns to be bad

“…Alagona et al [17] Asymptomatic subjects 89 Associated inversely with IMT No association with IMT Sharrett et al [18] Healthy subjects 12.339 Lower for cases Lower for cases Mora et al [19] Female subjects 27.673 Relative to lowest quintile No significance for medium and small size HDLs Williams et al [20] Healthy subjects 1905 Lowest quartile of HDL2-mass predicted greater incident CHD Lowest quartile of HDL3-mass predicted incident CHD Williams et al [21] CHD/controls 1905 Lowest HDL2-mass quartile increased the risk for total CHD and premature CHD Lowest HDL3-mass quartile increased the risk for total CHD and premature CHD Lamon-Fava et al [22] CHD 256 Coronary atherosclerosis progression unrelated Coronary atherosclerosis progression unrelated to changes. Greater progression for greater reductions.…”