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Physical activity, hypertension and risk of heart attack
234 PHYSICAL ACTIVITY, HEART ATTACK
J.R.l
A: I&ii&,:!
P.C. EIKIxI,~E.S. Link2
‘St. Msry’s Hxpital, Rxtzwxh. SRC Epidaniolqy Lhit, Gxdiff. ‘Sigh skariq forces ckwlqin stxctic arteries sd high shear activates platelets. knrdirgly in tk arrant recall of 2,oJI nul aged 55 - 69(89x of tk total available pqulaticn), the folle prinnry platelet WI-e cnr&&xd:- Plt cant (Plt) related B llEan Pit dw, fibrirqn (ad visckty and WZ): Lhiqdy in an epiWriokgical stdy thz folluxing cqlex tests wze irclwkd:- skin ble tinq Plt LX’ wticn (irrpedare) srd a hi& ekar filter Plt test. This latter glckd test cndde blozd rquires Nf, Plt glyccprotein n, srd CPIIb/IIIa. Ihis plxl pemdts ickntificaticn of correlaticns tetwzn tests; e.g. skin ETI is uuffeZed~variaticnswithintknxndzqeofNf ae aalte $sse reactsrlts WEC, Mf, ad fibrinqn. fibrirqen z-d viszdy, tut rnt IWII, are all intercorrelated in t+euLs~rlm. *repJrt th? adysis cn d-e first 1,0x) volu&ers in relation to A pxsible/pdable W, s&&-g and fish oil irgesticn. rudlx of tests axe similarly aszxxiated witll IHI ad 3 ad ~byf@hoil.%is5uggeststit tk nwhxun rmy~m~causallyto,ard rot h caud by, atkrcsclerc6is.
HIGH CLRLSROVASCUJ.AP IIJJSISTANCLS IN FMILrAJa ,,BSTggOJ,Ag”IA,
JWPSIWJJO-
PLJ.ATIONSJJIP UITJJ INTU9A-IIgDIA P.Rubbm.
lJ.!Jercuri+,
C. Irace,
P.Strisciuglio,
P.Caccenda,
A.lannuzzi,
R.Tang*.
C.Andris.
tJ.C.lknd*
A.Gmsso.
and f4.flancini. 2nd fkdicel
School
men Gray
Jledical
7en patients leeria agw
with
(man
tmderwent widdle
cerebral
~~ltraoound
artery
ilnging of
-n
arlrrinn.
an
index
velocity
nterolaemic nes ncular
was
I
haocystinuria
in
1.4
fwenc:es These
I
data
or
tients
are
Lho carotid
Doppler.
measure and
and
awwciated
to
carotid blood
in hyperchole-
hmcystinuric
o-
increased
intima-media
vethic-
JJypemJmleeterolemis. -
in
controls.
significant
high
vascular
of
0.6
The dif-
and homocystinu-
were
with
intime-media
internal
hypercholeaterolaic t.hat
over B-mode
Diastolic
raxilu 0.6
controls
met-
(pt0.002). reeistancrs
hypercholasterolaerir intima-media
in pa-
thickening
of
arteries.
dyafuction
awuiwd
invasive measured
suggesting
Familial
circulation
Intima-media lial
Nean
suggest
intracranial
non
reduced
compared
age
we8
atherosclerosis. as
in
between
patients
to bulb
(p
renistrmces. was
(2.3 yrs)
by
significanily
cxnltrols
kness
rir:
of
pat.ientR
nnd
used
thickening in
might
intracranial
mndotheliu-depndent
REDUCTASE OF INTIMAL
INHIBITORS CAROTID
Maurizio R. FUMAGALLI.
(VASTATINS): MYOCYTE
IN
VIVO
PROLIFERATION
RABBITS.
SOMA, Elena WNElTI, Rodolfo PAOLETTI
Cinzia
PAROLINI.
Remo
*Bow-
(mean
transcranisl
carotid,
-
Amcystinuria
velocity
by
was
thickness flow
Plow
Italy
Hypercholestero-
controls
examination
blood
HMGCoA
Salem.NC
Yslilial
11 healthy
a vascular
Cerebral
Naples.
JZ with
27 yrs).
and
of
Winston
hamoeygous
age
24 yrs)
hods.
University ScJmol.
An increased risk of heart attack has been observed in men who are vigorously active compared with those reporting more moderate levels of activity. Middle-aged British men free of pre-existing ischaemic heart disease (n = 5694) were followed for 9.5 years. Separation into normotensive and hypertensive groups revealed that the increased risk of heart attack with vigorous (sporting) activity was only seen in hypertensive men even after However, adjustment for other risk factors. the presence of other risk factors aggravated the increased risk in these men. Left ventricular hypertrophy on electrocardiogram and antihypertensive treatment were not involved in the increased risk and sudden death was not a feature of the phenomenon. Middle-aged men involved in or contemplating regular sporting activity should have their blood pressure measured, and if hypertensive, more detailed risk assessment is indicated.
IN NORMOCHOLESTEROLEMIC
TRICKKNTNC.
AND RISK OF
A.G. SHAPER, G. WANNAMETHEE, M. WALKER Dept of Public Health and Primary Care Royal Free Hospital School of Medicine LONDON Nh’3 2PF
INHIBITION
NOT IN JJO”OCYSTIN”HA.
HYPERTENSION
be
a marker arteries.
vasorelexation.
of
endothe-
leading
to
Sciences, University of Milan. ITALY Institute ofPharmacological The in viva direct antiatherogenic activity of different vastatins has been investigated on arterial rabbit smooth muscle cells (SMC) migration and proliferation in normocholesterolemic rabbits by assessing neointimal formation induced by the insertion of a collar around one carotid artery. The contralateral carotid served as sham. Pravastatin. lovastatin. simvastatin, and fluvastatin were given mixed with food at the doses of 20 m&g. daily for 2 weeks, starting from the day of collar insertion. The treatment with all drugs tested did not alter rabbit plasma lipid levels. The neointimal hyperplasia. mostly cellular. was followed by measuring cross-sectional thickness of intimal (I) and medial (M) tissue of fixed arteries with light microscopy. By 14 days after collar placement the arteries with no collar showed an I/M tissue ratio of 0.03 f 0.02, whereas in the carotids with collar the ratio was 12 fold higher (0.36 f 0.04). The animals receiving lovastatin. simvastatin. and fluvastatin showed a neointimal formation Pravastatin was less inhibited by 33%. 44%. and 53%. respectively. effective at this regard (11%). Immunofhmrescence analysis with a-actinSMC antibody revealed that nearly all cells present in the intimal layers were myocytes. Intimal myocyte proliferation was assessed by measuring the incorporation of 5-Bromo-2’deoxyuridine (BrDU), a thymidiie analogue, into replicating DNA. hnmunofluorescence analysis showed that BrDU was actively andselectively incorporated into DNA of intimal cells. Pravastatin. lovastatin. simvastatin. and fluvastatin reduced the incorporation ofBrDU in intimal myocytes by 7%, 39%. 43%. 45%. respectively. We conclude therefore that vastatins. with different efficacy, exert a direct antiproliferative effect on iniial myocytes independently from their effects on plasma lipids.
J.R.l
A: I&ii&,:!
P.C. EIKIxI,~E.S. Link2
‘St. Msry’s Hxpital, Rxtzwxh. SRC Epidaniolqy Lhit, Gxdiff. ‘Sigh skariq forces ckwlqin stxctic arteries sd high shear activates platelets. knrdirgly in tk arrant recall of 2,oJI nul aged 55 - 69(89x of tk total available pqulaticn), the folle prinnry platelet WI-e cnr&&xd:- Plt cant (Plt) related B llEan Pit dw, fibrirqn (ad visckty and WZ): Lhiqdy in an epiWriokgical stdy thz folluxing cqlex tests wze irclwkd:- skin ble tinq Plt LX’ wticn (irrpedare) srd a hi& ekar filter Plt test. This latter glckd test cndde blozd rquires Nf, Plt glyccprotein n, srd CPIIb/IIIa. Ihis plxl pemdts ickntificaticn of correlaticns tetwzn tests; e.g. skin ETI is uuffeZed~variaticnswithintknxndzqeofNf ae aalte $sse reactsrlts WEC, Mf, ad fibrinqn. fibrirqen z-d viszdy, tut rnt IWII, are all intercorrelated in t+euLs~rlm. *repJrt th? adysis cn d-e first 1,0x) volu&ers in relation to A pxsible/pdable W, s&&-g and fish oil irgesticn. rudlx of tests axe similarly aszxxiated witll IHI ad 3 ad ~byf@hoil.%is5uggeststit tk nwhxun rmy~m~causallyto,ard rot h caud by, atkrcsclerc6is.
HIGH CLRLSROVASCUJ.AP IIJJSISTANCLS IN FMILrAJa ,,BSTggOJ,Ag”IA,
JWPSIWJJO-
PLJ.ATIONSJJIP UITJJ INTU9A-IIgDIA P.Rubbm.
lJ.!Jercuri+,
C. Irace,
P.Strisciuglio,
P.Caccenda,
A.lannuzzi,
R.Tang*.
C.Andris.
tJ.C.lknd*
A.Gmsso.
and f4.flancini. 2nd fkdicel
School
men Gray
Jledical
7en patients leeria agw
with
(man
tmderwent widdle
cerebral
~~ltraoound
artery
ilnging of
-n
arlrrinn.
an
index
velocity
nterolaemic nes ncular
was
I
haocystinuria
in
1.4
fwenc:es These
I
data
or
tients
are
Lho carotid
Doppler.
measure and
and
awwciated
to
carotid blood
in hyperchole-
hmcystinuric
o-
increased
intima-media
vethic-
JJypemJmleeterolemis. -
in
controls.
significant
high
vascular
of
0.6
The dif-
and homocystinu-
were
with
intime-media
internal
hypercholeaterolaic t.hat
over B-mode
Diastolic
raxilu 0.6
controls
met-
(pt0.002). reeistancrs
hypercholasterolaerir intima-media
in pa-
thickening
of
arteries.
dyafuction
awuiwd
invasive measured
suggesting
Familial
circulation
Intima-media lial
Nean
suggest
intracranial
non
reduced
compared
age
we8
atherosclerosis. as
in
between
patients
to bulb
(p
renistrmces. was
(2.3 yrs)
by
significanily
cxnltrols
kness
rir:
of
pat.ientR
nnd
used
thickening in
might
intracranial
mndotheliu-depndent
REDUCTASE OF INTIMAL
INHIBITORS CAROTID
Maurizio R. FUMAGALLI.
(VASTATINS): MYOCYTE
IN
VIVO
PROLIFERATION
RABBITS.
SOMA, Elena WNElTI, Rodolfo PAOLETTI
Cinzia
PAROLINI.
Remo
*Bow-
(mean
transcranisl
carotid,
-
Amcystinuria
velocity
by
was
thickness flow
Plow
Italy
Hypercholestero-
controls
examination
blood
HMGCoA
Salem.NC
Yslilial
11 healthy
a vascular
Cerebral
Naples.
JZ with
27 yrs).
and
of
Winston
hamoeygous
age
24 yrs)
hods.
University ScJmol.
An increased risk of heart attack has been observed in men who are vigorously active compared with those reporting more moderate levels of activity. Middle-aged British men free of pre-existing ischaemic heart disease (n = 5694) were followed for 9.5 years. Separation into normotensive and hypertensive groups revealed that the increased risk of heart attack with vigorous (sporting) activity was only seen in hypertensive men even after However, adjustment for other risk factors. the presence of other risk factors aggravated the increased risk in these men. Left ventricular hypertrophy on electrocardiogram and antihypertensive treatment were not involved in the increased risk and sudden death was not a feature of the phenomenon. Middle-aged men involved in or contemplating regular sporting activity should have their blood pressure measured, and if hypertensive, more detailed risk assessment is indicated.
IN NORMOCHOLESTEROLEMIC
TRICKKNTNC.
AND RISK OF
A.G. SHAPER, G. WANNAMETHEE, M. WALKER Dept of Public Health and Primary Care Royal Free Hospital School of Medicine LONDON Nh’3 2PF
INHIBITION
NOT IN JJO”OCYSTIN”HA.
HYPERTENSION
be
a marker arteries.
vasorelexation.
of
endothe-
leading
to
Sciences, University of Milan. ITALY Institute ofPharmacological The in viva direct antiatherogenic activity of different vastatins has been investigated on arterial rabbit smooth muscle cells (SMC) migration and proliferation in normocholesterolemic rabbits by assessing neointimal formation induced by the insertion of a collar around one carotid artery. The contralateral carotid served as sham. Pravastatin. lovastatin. simvastatin, and fluvastatin were given mixed with food at the doses of 20 m&g. daily for 2 weeks, starting from the day of collar insertion. The treatment with all drugs tested did not alter rabbit plasma lipid levels. The neointimal hyperplasia. mostly cellular. was followed by measuring cross-sectional thickness of intimal (I) and medial (M) tissue of fixed arteries with light microscopy. By 14 days after collar placement the arteries with no collar showed an I/M tissue ratio of 0.03 f 0.02, whereas in the carotids with collar the ratio was 12 fold higher (0.36 f 0.04). The animals receiving lovastatin. simvastatin. and fluvastatin showed a neointimal formation Pravastatin was less inhibited by 33%. 44%. and 53%. respectively. effective at this regard (11%). Immunofhmrescence analysis with a-actinSMC antibody revealed that nearly all cells present in the intimal layers were myocytes. Intimal myocyte proliferation was assessed by measuring the incorporation of 5-Bromo-2’deoxyuridine (BrDU), a thymidiie analogue, into replicating DNA. hnmunofluorescence analysis showed that BrDU was actively andselectively incorporated into DNA of intimal cells. Pravastatin. lovastatin. simvastatin. and fluvastatin reduced the incorporation ofBrDU in intimal myocytes by 7%, 39%. 43%. 45%. respectively. We conclude therefore that vastatins. with different efficacy, exert a direct antiproliferative effect on iniial myocytes independently from their effects on plasma lipids.