Evaluation of Serum Lipoprotein and Cholesterol Measurements as Predictors of Clinical Complications of Atherosclerosis

Gofman, John W.; Hanig, Martin; Jones, Hardin B.; Lauffer, Max A.; Lawry, Eleanor Y.; Lewis, Lena A.; Mann, George V.; Moore, Felix E.; Olmsted, Frederick; Yeager, J. Franklin; Andrus, E. Cowles; Barach, Joseph H.; Beams, J. W.; Fertig, John W.; Page, Irvine H.; Shannon, James A.; Stare, Fredrick J.; White, Paul D.

doi:10.1161/01.cir.14.4.689

Cited by 163 publications

(22 citation statements)

References 25 publications

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“…The 5-year survival of 79 per cent, calculated from date of first infarct, is similar to that of other goodrisk groups in the literature'8-21 and confirms a recent editorial opinion.22 The indifference of survival to the age of the patient, as shown in figure 3, is similar to the experience of Honey and Truelove19 However, in comparison to life expectancy of healthy insured Canadian men, the ratio of actual to expected deaths was much greater for the younger than for the older coronary patients, as shown in table 5. Similar comparisons have been made in previous publications.20 '23 Of course this does not indicate more "malignant" disease in the younger patients with coronary heart disease.…”

Section: Survival and Serum Lipoproteinssupporting

confidence: 80%

Studies of Male Survivors of Myocardial Infarction

et al. 1965

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This study examined life expectancy and serum lipids in 120 men with atherosclerotic coronary heart disease. Five-year survival from onset of infarction was 79 per cent. No relationship could be demonstrated between survival and the level of the total serum cholesterol, Std. S f 0-12, 12-20, 20-100, and 100-400 lipoproteins. Survival for patients with an infarct less than 6 months before entry into the study was shorter, despite serum lipid levels the same as the remainder of the group. Although the age of onset of coronary disease is influenced by serum lipid levels, survival subsequent to infarction is not. This paradox suggests that serum lipids affect rate of atherogenesis in the long preclinical stage but in the short clinical stage other factors determine survival.

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Section: Survival and Serum Lipoproteinssupporting

confidence: 80%

Studies of Male Survivors of Myocardial Infarction

et al. 1965

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“…Table 2 addresses two fundamental questions proposed 60 years ago by Gofman and colleagues: i ) whether analytic ultracentrifuge measurements of particular lipoproteins were specifi cally related to CHD and ii ) whether particular lipoproteins accounted for serum cholesterol's relationship to CHD. In 1950, the multicenter Cooperative Study (Cleveland Clinic, University of Pittsburgh, Harvard School of Public Health, and Donner Laboratory) was established to test prospectively in 5,000 middle-aged men whether the analytic ultracentrifuge's lipoprotein measurements were a better predictor of cardiac events than total serum cholesterol levels ( 18 ). The study, plagued with diffi culties in recruitment and in standardizing measurements across clinics, also had the problem of dealing with Gofman's evolving methodology during the study.…”

Section: Discussionmentioning

confidence: 99%

“…The men are limited to the 1,905 subjects of Gofman's original report who were free of prior ischemic heart disease at baseline. The criteria for entry into the study presumably corresponded to the criteria adopted by the Cooperative Study, which evaluated the predictive value of serum low-density lipoprotein fractions and total cholesterol on clinical complications of atherosclerosis, in which Gofman participated ( 18 ). Namely, potential subjects were disqualifi ed on the basis of more than trace amounts of urine protein or sugar; diabetes mellitus; nephritis (except past history of pyelonephritis, nephrolithiasis, or loss of kidney); treatment with ACTH, cortisone, or related hormones; history of rheumatic heart disease; known congenital heart disease; or syphilis or Buerger's disease.…”

Section: Methodsmentioning

confidence: 99%

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

Williams

2012

Journal of Lipid Research

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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 ...

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“…1 In the 1950s, flotation fractionation of lipoproteins was developed. 2 This method allowed investigation of lipoproteins of different densities and identified the elevations of low density lipoproteins as being particularly associated with coronary heart disease (CHD). At this time, the risk connected with low levels of high-density lipoproteins was also discovered but went into eclipse for some 20 years.…”

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confidence: 99%