Cigarette Smoking-Associated Changes in Blood Lipid and Lipoprotein Levels in the 8-to 19-Year-Old Age Group: A Meta-Analysis

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Cigarette

Smoking-Associated

Changes

in

Blood

Lipid

and

Lipoprotein

Levels

in the

8- to

19-Year-Old

Age

Group:

A Meta-Analysis

Wendy

Y. Craig,

PhD; Glenn

E. Palomaki,

BS; A. Myron

Johnson,

MD;

and James

E. Haddow,

MD

From the Foundation for Blood Research, Scarborough, Maine

ABSTRACT.

In this meta-analysis it was demonstrated

that, when compared with nonsmokers of similar age,

smokers in the 8- to 19-year-old age group have

signifi-cantly higher serum levels of triglyceride (+11.8%), very-low-density lipoprotein (VLDL)-cholesterol (+12.4%)

and low-density lipoprotein (LDL)-cholesterol (+4.1%) and significantly lower serum levels of high-density

lip-oprotein (HDL)-cholesterol (-8.5%) and total cholesterol (-3.7%). All of these smoking-associated changes are in

the same direction as those found in adults, with the exception of total cholesterol levels, which are

signifi-cantly increased in adult smokers. The extent to which

mean triglyceride, LDL-cholesterol, and

HDL-choles-terol levels are shifted is significantly greater in the 8- to

19-year-old smokers than in adult smokers. The changes

in mean total cholesterol levels among smokers in both

age groups represent only the net shifts in the lipoprotein

fractions and are therefore likely to be a less sensitive

indicator of the possible lipid-related excess coronary

artery disease risk in smokers. Pediatrics 1989;85:155-158; smoking, cholesterol, lipoprotein, meta-analysis.

ABBREVIATIONS. HDL, high-density lipoprotein; LDL,

low-density lipoprotein; VLDL, very-low-density lipoprotein.

that cigarette smoke exposure produces oxidized low-density lipoprotein (LDL) and that these mod-ified LDLs cause the accumulation of cholesteryl

esters in macnophages. Thus, oxidation of LDL

might also contribute to foam cell formation and atherosclerosis in smokers.6 We have recently ana-lyzed the available published data concerning the effects of cigarette smoking on serum lipid and lipoprotein levels in adults7; cigarette smokers have significantly increased serum levels of total choles-terol, triglycerides, very-low-density lipopnotein

(VLDL)-cholestenol and LDL-cholesterol and

sig-nificantly decreased serum levels of high-density

lipopnotein (HDL)-cholesterol and

apolipoprotein-Al. Apolipoprotein-Al is the major protein associ-ated with HDL. The purpose of the present study

is to analyze these variables in the 8- to

19-year-old age group, using the same approach, and thus to determine whether these smoking-associated changes in lipid and lipopnotein levels are also present in a younger population.

METHODS

Cigarette smoking is associated with an increased risk for coronary artery disease.’ A variety of smok-ing-associated physiologic changes are likely to con-tribute to that increased risk, including altered blood lipid levels, increased carboxyhemoglobin 1ev-els, and increased clotting factor concentrations and blood viscosity, all of which have been observed

in adult smokens.25 In vitro studies have shown

Received for publication Feb 21, 1989; accepted Mar 27, 1989. Reprint requests to (J.E.H.) Foundation for Blood Research, P0 Box 190, Scarborough, ME 04074.

The methods used for identifying and selecting the scientific publications have been described in

detail previously.7 Briefly, articles were identified

using the MEDLINE search facility (1966 to 1987) and the literature data base of the Office on Smok-ing and Health (US Department of Health and

Human Services, Rockville, MD); the reference lists

of these articles were then reviewed to identify additional studies. Mass unit data were required for the present analysis; therefore, those studies in which the data were reported solely in the form of

regression coefficients were excluded. For the

pres-ent analysis involving the 8- to 19-year-old age

group, available published data were found to be

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156 LIPOPROTEINS

AND

SMOKING

cigarette smoking on serum total cholesterol,

tn-glycerides, VLDL-cholesterol, LDL-cholesterol,

and HDL-cholestenol levels.’4 Because only one article dealt with the dose-response effects of

smok-ing,’3 the present analysis was confined to a

com-panison of nonsmokers and all current smokers. Of the seven studies, in five, only current smoking

status was considered in defining smokers and

non-smokens.’1”4 Of the remaining studies, in one,

never-smokers and ex-smokens were identified, but the data were combined in a single group,’2 and in the other separate data were presented for

never-smokers and ex-smokens’3; in this case, nonsmokers

were defined as never-smokers.

In our analysis of the combined studies, the data were normalized for each variable by expressing the difference between smokers and nonsmokers in each study as a Z scone, to account for variations

between laboratory assays and populations and for the fact that in three of the seven studies9”#{176}”4 plasma, not serum, levels of the different variables were measured. For practical purposes, serum levels refer to either serum on plasma levels in this article. A Z score is the difference between smokers and nonsmokers for a given variable divided by the pooled standard deviation for that variable in a given study.

To estimate the effect of smoking on each van-able, a mean Z score was calculated, weighted by

the square of the pooled standard error of each

study to take into account different-sized study

populations and assay variability. Significance

test-ing was performed on the weighted mean Z scone, and the level of significance was determined by Student’s ttest. The mean percentage difference in

a variable between smokers and nonsmokers was estimated by multiplying the weighted mean Z scone

by the overall pooled standard deviation.

The mathematical methods employed in

compil-ing and analyzing the data have been published in

detail elsewhere.7

RESULTS

In Table 1, the sources of the data included in

the present analysis are described. In the Table, the

pertinent references are listed and information is provided concerning both the populations studied and the variables measured in each case. The ages of subjects in the seven studies range collectively between 8 and 19 years of age and all groups include both boys and girls. HDL-cholestenol

measure-ments are available in seven studies, total

choles-tenol in six, triglycerides and LDL-cholestenol in

five, and VLDL-cholestenol in four studies. In Table 2, we summarized the effects of cigarette

smoking on serum lipid and lipoprotein levels in the 8- to 19-year-old age group derived from

ana-lyzing data contained in the reports listed in Table

1. Serum triglyceride, VLDL-cholestenol, and

LDL-cholesterol levels are significantly increased, whereas total cholesterol and HDL-cholesterol

1ev-els are significantly decreased in smokers compared

to nonsmokers. The data for adults, published

pre-viously,7 are provided in the night-hand column to

allow direct comparison with the results from the younger age group. The smoking-associated changes in triglyceride, VLDL-cholestenol, LDL-cholesterol, and HDL-cholestenol levels are in the

same direction in the two groups, although the

magnitude of the effects, with the exception of VLDL-cholestenol, is significantly greaten in the younger age group. Serum total cholesterol levels increase significantly in adults and decrease

signif-icantly in younger smokers.

TABLE 1.

Available P

Cigarette Smoking and Serum ublished Data for the 8- to 19-Ye

Lipids ar-Old

and Lipoproteins: A Summary of Age Group*

Reference

0.

Population Characteristics Variables Available Comments

Age Range No. of No. of Non-(y) Smokers smokers

C T VLDL-C LDL-C HDL-C

8 9-17 145 562 X X X X X A, B

9 12-19 66 641 X X X X X B

10 12-19 105 105 X X X X

11 13-18 99 485 X X A

12 14-17 87 334 X X X X X B

13 8-17 280 497 X B

14 17 313 919 X X X X X B

* Abbreviations: C, total serum cholesterol; T, triglycerides; VLDL-C, very low density lipoprotein-cholesterol; LDL-C, low density lipoprotein-cholesterol; HDL-C, high density lipoprotein-cholesterol; X, data for this variable is available. Key to “Comments”: A = standard deviation not reported, but estimated using pooled variance of remaining studies;

B = value(s) reported as weighted average of subgroups.

at Viet Nam:AAP Sponsored on September 12, 2020 www.aappublications.org/news

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TABLE 2.

8- to 19-Yea

Effect of Cigarette Smoking on Serum Lipid and Lipoprotein Levels in the r-Old Age Group: Analysis of Published Data and Comparison With Adults* Variable Current Smokers vs Nonsmokers in the Current Smokers vs Nonsmokers

8- to 19-Year-Old Age Group Among Adults

No. of Z Score (Mean % Differ- No. of Studies ± SE) ence Studies Ct

Tt VLDL-C LDL-Ct HDL-Ct

6 -0.197 ± 0.040 -3.7 22 5 0.215 ± 0.044 +11.8 13 4 0.175 ± 0.047 +12.4 5 5 0.158 ± 0.044 +4.1 16

7 -0.366 ± 0.036 -8.5 22

z Score (Mean

0.163 ± 0.010

0.139 ± 0.020 0.142 ± 0.024 0.069 ± 0.024 -0.234 ± 0.013

* Abbreviations: C, total serum cholesterol; T, triglycerides; VLDL-C, very-low-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol.

t Significant difference between adults and 8- to 19-year-old age group. P < .001 by Student’s t test.

1:

Significant difference between smokers and nonsmokers, P < .05 by Student’s t test for all variables listed below.

§

Percentage of difference in the value of a given variable, compared with the variable among nonsmokers.

%

Differ-ence +3.0 +9.1 +10.4 +1.7 -5.7

DISCUSSION

In the 8- to 19-year-old age group, cigarette smok-ing-associated changes in serum lipid and lipopro-tein levels are, with the exception of total choles-tenol, in the direction of increased risk for coronary

artery disease and are in the same direction as those found in adults. With the exception of cholesterol, insufficient prospective data are available to allow an estimation of the proportion of excess risk for coronary artery disease in smokers that might be attributed to altered lipid on lipopnotein levels. Pre-liminany data, however, indicate that lower levels of HDL-cholestenol and higher levels of

LDL-cho-lestenol may be associated with increased risk.’5”6

Given the changes in the lipid and lipoprotein

van-ables, it is reasonable to assume that increased risk does exist, even among smokers in the 8- to 19-year-old age group, for the onset of coronary artery disease later in life. Moreover, because the degree of change in triglyceride, LDL-cholestenol, and HDL-cholestenol levels is significantly greaten in younger smokers than in adults, the risk may ac-tually be greater in this population.

Changes in serum total cholesterol levels associ-ated with smoking in various age groups represent the sum of a net decrease in HDL-cholestenol levels

and net increases in VLDL- and LDL-cholestenol

levels and thus do not accurately reflect underlying adverse changes in lipoprotein concentrations. The lower mean total cholesterol level associated with smoking in the 8- to 19-year-old age group is a good

example of this and, if taken alone, might actually be misleading in risk evaluation.

Autopsy studies indicate that the development of coronary artery disease begins in childhood in

west-em populations.’7 It is therefore important to iden-tify potential risk factors early, when prophylactic

cane might be most effective. The finding that

cen-tam lipid and lipopnotein levels in the 8- to

19-year-old age group are affected similarly to those of

adults in response to cigarette smoke exposure un-denscores once again the importance of

interven-tions to decrease cigarette consumption.

REFERENCES

1. The health consequences ofsmoking: cardiovascular disease. In A Report of the Surgeon General 1983. Rockville, MD: US Dept of Health and Human Services

2. McGill HC Jr. Potential mechanisms for the augmentation of atherosclerosis and atherosclerotic disease by cigarette smoking. Prey Med. 1979;8:390-403

3. Topping DL. Effects of tobacco smoke and its constituents on lipid and carbohydrate metabolism. In Clements MJ, Ashwell M, eds. Biockemistry of Cellular Regulation. Boca

Raton, FL: CRC Press mc; 1980;2:165-183

4. Pozner H, Billimoria JD. Effect ofsmoking on blood clotting and lipid and lipoprotein levels. Lancet. 1970;1:1318-21

5. Ernst E, Koenig W, Matrai A, et al. Blood rheology in healthy cigarette smokers: results from the MONICA proj-ect. Augsberg. Arteriosclerosis. 1988;8:385-388

6. Yokode M, Kits T, Arai M, et al. Cholesteryl ester accu-mulation in macrophages incubated with low density lipo-protein pretreated with cigarette smoke extract. Proc Nati Acad Sci USA. 1988;85:2344-2348

7. Craig WY, Palomaki GE, Haddow JE. Cigarette smoking

and serum lipid and lipoprotein levels: an analysis of pub-lished data. Br Med J. 1989;298:784-788

8. Freedman DS, Srinivasan SR, Shear CL, et al. Cigarette smoking initiation and longitudinal changes in serum lipids and lipoproteins in early adulthood: the Bogalusa Heart Study. Am J Epidemiol. 1986;124:207-219

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158 LIPOPROTEINS

AND

SMOKING

10. Morrison JA, Kelly K, Mellies M, et a!. Cigarette smoking, alcohol intake and oral contraceptives: relationships to lip-ids and lipoproteins in adolescent school children.

Metabo-lism.1979;28:1166-1170

11. Orchard TJ, Rodgers M, Hedley AJ, et al. Changes in blood lipids and blood pressure during adolescence. Br Med J.

1980;280:1563-1567

12. Webber LS, MacD. Hunter 5, et al. The interaction of cigarette smoking, oral contraceptive use, and cardiovascu-lar risk factor variables in children: the Bogalusa Heart Study. Am J Public Health. 1982;72:266-274

13. Voors AW, Srinivasan SR, MacD. Hunter 5, et al. Smoking, oral contraceptives and serum lipid and lipoprotein levels in

youths. Prey Med. 1982;11:1-12

14. Halfon S-T, Kark JD, Baras M, et al. Smoking, lipids and lipoproteins in Jerusalem 17-year-olds. Israel J Med Sci.

1982;18:1150-1157

15. Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary heart disease. Am J Med. 1977;62:707-714

16. Kannel WB, Lerner DJ. Present status of risk factors for atherosclerosis. Med Times. 1984;112:33-45

17. McGill HC Jr, GeerJC, StrongJP. Natural history of human atherosclerotic lesions. In Sandier M, Bourne GH eds. Ath-erosclerosis and Its Origins. New York, NY: Academic Press; 1963:39ff

THE COSTS OF CURES

What is a fain price for a miracle drug? $8,000 a year? $6,000? $100? Should it be given away for nothing? Questions such as these arrive from the recent controversy oven the pricing of AIDS drug AZT, which is sold by Burroughs

Wellcome Co. Protesting the drug’s annual cost of about $8,000, AIDS

demon-stratons recently chained themselves to the visitors gallery at the New York Stock Exchange...

Congressman Henry Waxman, a longtime critic of the drug industry’s prices, criticized Wellcome oven AZT, adding, “Congress has the responsibility to ensure that this lifesaving drug is available to everyone. . .and through a

reason-able price to all.” While Congress is now considering an extension of its program of federal payments to individuals using AIDS drugs, Mn. Waxman’s remarks raise another familiar threat-price controls on pharmaceuticals...

The bureaucratic delays that have engulfed the federal AIDS effort are reason

enough to leave drug development to private companies.

However, if we can agree that a drug’s development costs contribute to its

final price, one way to cut the price deserves consideration: Reduce the number and scale of clinical trials required to support proof of the drug’s efficacy prior to putting it on the market. An analysis by Arthur D. Little estimated that the largest clinical trials normally required by the FDA, so-called Phase-3 tests, typically account for about 30% of a drug’s total development cost...

The FDA and many researchers would resist giving up any degree of the

statistical comfort (and work) provided by these huge, costly, labor-intensive trials. And many of the people who complain about the high price of prescription

drugs are the same ones who most vociferously defend the FDA’s current,

expensive system of approval. But they can’t have their cake and eat it too on

this. Either defend the status quo and stop complaining about the resulting costs, on rethink the status quo. If indeed getting drugs to the seriously ill at a reasonable price is a legitimate issue, this country ought to think about revising its gold-plated system of lange-scale clinical trials.

From The costs of cures. The Wall Street Journal. Oct 4, 1989

Noted by J.F.L., MD

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1990;85;155

Pediatrics

Wendy Y. Craig, Glenn E. Palomaki, A. Myron Johnson and James E. Haddow

8-to 19-Year-Old Age Group: A Meta-Analysis