Frick m h, elo o, haapa k, heinonen o p, heinsalmi p, helo p, huttunen j k, kaitaniemi p, koskinen p, manninen v, maenpaa h, malkonen m, manttari m, norola s, pasternack a, pikkarainen j, romo m. sjöblom t & nikkilä e a.n. engl. j. med.317:1237-45, 198
This Week's Citation Classic
Frick M H, Elo O, Haapa K, Heinonen O P, Heinsalmi P, Helo P, Huttunen J K,
Kaitaniemi P, Koskinen P, Manninen V, Maenpaa H, Malkonen M, Manttari M,
Norola S, Pasternack A, Pikkarainen J, Romo M. Sjöblom T & Nikkilä E A.
Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with
dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart
disease. N. Engl. J. Med.
[First and Third Depts. Medicine. Univ. Helsinki; National Public Health Inst.: Finnish Railways. Posts
and Telecommunications: Enso-Gutzeit: Veitsiluto. Helsinki: Dept. Medicine. Univ. Tampere;
A. Ahlstrom. Karhula; Kaukas (Kymmene), Lappeenranta: and Neste. Paardeweide, Finland]
This multicenter, prospective lipid-modulating
Compliance to medication was rigorously
study showed for the first time that increasing the
checked by three methods and found excellent.
level of high-density lipoprotein cholesterol re-
Not a single person was lost to follow-up. This is
duced the incidence of coronary heart disease in
because people in Finland do not frequently
change address and because the nursing staff
dyslipidemic but otherwise healthy middle-aged
in "front line service" was very efficient. One
men. [The SCI® indicates that this paper has
rewarding experience was to keep this staff of
■ been cited in more than 900 publications.]
more than 100 persons motivated over five years.
(One way to do it is to charter an airplane and
organize a meeting at the Royal College of Nurs-
ing in London.)
We knew from previous studies that blood
should be sampled abundantly. As the years
First Department of Medicine
pass by, new factors associated with CHD
Helsinki University Central Hospital
emerge. Blood samples from a large, prospec-
00290 Helsinki, Finland
tive study render new analyses possible, and
The thesis that the level of high-density lipo-
have done so in conjunction with the HHS.
protein (HDL) cholesterol is inversely related to
However, when you are dealing with blood
the occurrence of coronary heart disease (CHD)
samples from some 19,000 individuals you must
was presented some 40 years ago.1,2 This dis-
remember to include the rent of a warehouse
covery did not gain the full acceptance of the
into your budget calculations.
lipid researchers of those years, notably Ancel
Our group was originally chaired by E.A.
Keys, and its further exploration was put to
Nikkila, a pioneer in HDL research. After his
hibernation. The chapter was reopened by demise in a traffic accident I had the privilege to
Norman Miller in 19753 leading to a proliferation
take over. As a clinical cardiologist, although
of HDL research. Since cross-sectional and ob-
one involved in lipid research for over 20 years,
servational studies could not fulfill Koch's pos-
I believe that the HHS has been a great experi-
tulates, a prospective, lipid-modulating study,
ence shared by all members of the team, which
the Helsinki Heart Study (HHS), was initiated.
consists of experts in biostatistics, public health,
The HHS used gemfibrozil to increase HDL cho-
internal medicine, cardiology, and occupational
lesterol in dyslipidemic individuals. Detailed medicine. We have not received any awards or
analyses of the relationships between lipid specific honors, but we have had the opportu-
changes and a 34 percent reduction in CHD
nity to furnish new substrate to the discussion
incidence revealed that both an increase in HDL
about lipids and CHD.
cholesterol and a decrease in low-density lipo-
Concerning the role of HDL cholesterol in
protein (LDL) cholesterol contributed to the out-
CHD, researchers can be divided into believers
come." The series included a very high risk and nonbelievers. Our article, selected as a subgroup characterized by elevated triglycer-
Citation Classic', has evidently been cited more
ides, low HDL cholesterol, and high LDL/HDL
by the former category. We have also been able
ratio.5 In this subgroup the therapy decreased | to survive both random sniping and frontal as- the CHD incidence by some 70 percent.
I saults by the latter category.
1. Barr D P. Russ E M & Eder H A.
Prolein-lipid relationships in human plasma I I . In atherosclerosis and refilled
Ainer. J. Med
11:480-93. 1951. (Cited 495 t i m e s . ) 2 . Nikkilä E.
Studies on the itpid-prolein relationships in
normal and pathological sera and the effect of heparin on serum
hpoproleins. Scand. J. Clin. Lab. Invest 5(
Supp .8): 1-101. 1953. (Cited 145 times.) 3. Miller G J & Miller N E.
Plasma-high-density -lipoprotein concentration and development of ischaemic heaat-disease.
1:16-9. 1975. (Cited 2,010 times.) [See also: Miller G J.
Citation Classic (Barren .J T. ed.) Contemporary
classics in t h e l i f e s c i e n c e s . V o l u m e , 2 : t h e m o l e c u l e s l i f e :
P h i l a d e l p h i a : I S I P r e s s . 1 9 8 6 . p . 4 1 . ] 4 . Manninen V. Elo
O. Frick M H. Haapa K. Heinonen O P, Heinsalmi P. Helo P. Hutlunen J K. Kaitaniemi P. Koskinen P,
Maenpaa H. Malkonen M. Manttari M, Norola S. Pasternak A. Pikkarainen J, Komu M. Sjoblom T & Nikkila E A.
Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.
JAMA-J Am. Med Assn.
260:641 - 5 1 . 1988. (Cited 250 times.) 5. Manninen V, Tenkanen L. Koskinen P. Huttunen J K. Manttari M.
Heinonen O P & Frick M H.
Joint eftects of serum
trigyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study
:37-45, 1992 Received July 22. 1993.
CURRENT CONTENTS® 1993 by ISI®
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Mechanism of photoinhibition: magnetic field effect, singlet oxygen and kinetics Esa Tyystjärvi1, Marja Hakala-Yatkin1, Päivi Sarvikas1, Heta Mattila1, Sirin Dönmez1, Taina Tyystjärvi1, Petriina Paturi2, Ladislav Nedbal3 1Molecular Plant Biology, Department of Biochemistry and Food Chemistry, FI-20014 University of Turku, Finland; 2Department of Physics, FI-20014 University of Turku, Fi