Whether
statins should be given in the evening or in the morning,1 if at all,
depends on whether it is advisable to lower cholesterol as much or as little as
possible. There is much evidence for the latter, because in all clinical2,3
and angiographic4 trials, where dose-response was calculated, the
outcome was independent on the degree of cholesterol lowering, indicating that
the effect of the statins is due to other mechanisms. In favour of the latter
view is also that in almost all cohort studies of old people high cholesterol
was not a risk factor for coronary5-10 or total5,7,11-13
mortality and has even been associated with longevity,10,14-17 and,
in Russia, with cardiovascular health.18 These findings have been
ignored or belittled as minor aberrations from the LDL receptor hypothesis, but
considering that more than 90 per cent of all cardiovascular disease occur in
people above age 60, it is in fact one of the most serious blows against it. Why
should we lower cholesterol if a high cholesterol is unimportant or beneficial?
It may be fruitful to search for a drug with the same effects on the
cardiovascular system as the statins but without influencing cholesterol
synthesis. In the meantime it seems worth while to test the lowest, effective
statin dose instead of trying to lower cholesterol as much as possible.
Wallace
A, Chinn D, Rubin G. Taking simvastatin in the morning compared with in the
evening: randomised controlled trial. BMJ 2003; 327: 788 [Full
text]
Sacks
FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald
E. Relationship between plasma LDL concentrations during treatment with
pravastatin and recurrent coronary events in the cholesterol and recurrent
events trial. Circulation. 1998; 97: 1446-52 [Full
Text]
Schwartz
GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman
BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin
on early recurrent ischemic events in acute coronary syndromes: the MIRACL
study: a randomized controlled trial. JAMA
2001; 285:1711-8. [Pub
Med]
Ravnskov
U. Is atherosclerosis caused by high cholesterol? QJM2002; 95:
397-403. [Full
text]
Siegel
D, Kuller L, Lazarus NB, Black D, Feigal D, Hughes G, Schoenberger JA,
Hulley SB. Predictors of cardiovascular events and mortality in the Systolic
Hypertension in the Elderly Program pilot project. Am
J Epidemiol 1987; 126:385-9. [PubMed]
Nissinen
A, Pekkanen J, Porath A, Punsar S, Karvonen MJ. Risk factors for
cardiovascular disease among 55 to 74 year-old Finnish men: a 10-year
follow-up. Ann Med1989; 21:239-40. [PubMed]
Krumholz
HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI,
Tsukahara R, Ostfeld AM, Berkman LF.Lack
of association between cholesterol and coronary heart disease mortality and
morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272: 1335-40 [Pub
Med]
Weijenberg
MP, Feskens EJ, Bowles CH, Kromhout D.Serum total cholesterol and systolic blood
pressure as risk factors for mortality from ischemic heart disease among
elderly men and women. J
Clin Epidemiol1994; 47:197-205. [PubMed].
Simons
LA, McCallum J, Friedlander Y, Simons J. Diabetes, mortality and coronary
heart disease in the prospective Dubbo study of Australian elderly. Aust
N Z J Med1996; 26:66-74. [PubMed]
Räihä
I, Marniemi J, Puukka P, Toikka T, Ehnholm C, Sourander L. Effect of serum
lipids, lipoproteins, and apolipoproteins on vascular and nonvascular
mortality in the elderly. Arterioscler Thromb Vasc
Biol1997; 17:1224-32. [Full
Text]
Zimetbaum
P, Frishman WH, Ooi WL, Derman MP, Aronson M, Gidez LI, Eder HA. Plasma
lipids and lipoproteins and the incidence of cardiovascular disease in the
very elderly. The Bronx aging study. Arterioscl Thromb1992; 12:
416-423. [Pub
Med]
Fried
LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, Robbins JA,
Gardin JM.Risk factors for
5-year mortality in older adults: the Cardiovascular Health Study. JAMA
1998; 279:585-92.
[PubMed]
Chyou
PH, Eaker ED.Serum cholesterol concentrations and
all-cause mortality in older people. Age Ageing 2000; 29:69-74. [Full
Text]
Forette
B, Tortrat D, Wolmark Y. Cholesterol as risk factor for mortality in elderly
women.Lancet
1989; 1:868-70. [Pub
Med]
Weverling-Rijnsburger
AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total
cholesterol and risk of mortality in the oldest old. Lancet 1997;
350:1119-23. [PubMed]
Jonsson
A, Sigvaldason H, Sigfusson N. Total cholesterol and mortality after age 80
years. Lancet1997; 350:1778-9.
Schatz
IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and
all-cause mortality in elderly people from the Honolulu Heart Program: a
cohort study.Lancet
2001; 358:351-5. [Pub
Med]
Shestov
DB, Deev AD, Klimov AN, Davis CE, Tyroler HA. Increased risk of coronary
heart disease death in men with low total and low-density lipoprotein
cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study.
Circulation 1993; 88:846-53. [Pub
Med]
Rapid Response:
Serum cholesterol - a surrogate outcome
Whether
statins should be given in the evening or in the morning,1 if at all,
depends on whether it is advisable to lower cholesterol as much or as little as
possible. There is much evidence for the latter, because in all clinical2,3
and angiographic4 trials, where dose-response was calculated, the
outcome was independent on the degree of cholesterol lowering, indicating that
the effect of the statins is due to other mechanisms. In favour of the latter
view is also that in almost all cohort studies of old people high cholesterol
was not a risk factor for coronary5-10 or total5,7,11-13
mortality and has even been associated with longevity,10,14-17 and,
in Russia, with cardiovascular health.18 These findings have been
ignored or belittled as minor aberrations from the LDL receptor hypothesis, but
considering that more than 90 per cent of all cardiovascular disease occur in
people above age 60, it is in fact one of the most serious blows against it. Why
should we lower cholesterol if a high cholesterol is unimportant or beneficial?
It may be fruitful to search for a drug with the same effects on the
cardiovascular system as the statins but without influencing cholesterol
synthesis. In the meantime it seems worth while to test the lowest, effective
statin dose instead of trying to lower cholesterol as much as possible.
A, Chinn D, Rubin G. Taking simvastatin in the morning compared with in the
evening: randomised controlled trial. BMJ 2003; 327: 788 [Full
text]
FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald
E. Relationship between plasma LDL concentrations during treatment with
pravastatin and recurrent coronary events in the cholesterol and recurrent
events trial. Circulation. 1998; 97: 1446-52 [Full
Text]
GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman
BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive
Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin
on early recurrent ischemic events in acute coronary syndromes: the MIRACL
study: a randomized controlled trial. JAMA
2001; 285:1711-8. [Pub
Med]
U. Is atherosclerosis caused by high cholesterol? QJM2002; 95:
397-403. [Full
text]
D, Kuller L, Lazarus NB, Black D, Feigal D, Hughes G, Schoenberger JA,
Hulley SB. Predictors of cardiovascular events and mortality in the Systolic
Hypertension in the Elderly Program pilot project. Am
J Epidemiol 1987; 126:385-9. [PubMed]
A, Pekkanen J, Porath A, Punsar S, Karvonen MJ. Risk factors for
cardiovascular disease among 55 to 74 year-old Finnish men: a 10-year
follow-up. Ann Med1989; 21:239-40.
[PubMed]
HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI,
Tsukahara R, Ostfeld AM, Berkman LF.Lack
of association between cholesterol and coronary heart disease mortality and
morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272: 1335-40 [Pub
Med]
MP, Feskens EJ, Bowles CH, Kromhout D.Serum total cholesterol and systolic blood
pressure as risk factors for mortality from ischemic heart disease among
elderly men and women. J
Clin Epidemiol1994; 47:197-205. [PubMed].
LA, McCallum J, Friedlander Y, Simons J. Diabetes, mortality and coronary
heart disease in the prospective Dubbo study of Australian elderly. Aust
N Z J Med1996; 26:66-74. [PubMed]
I, Marniemi J, Puukka P, Toikka T, Ehnholm C, Sourander L. Effect of serum
lipids, lipoproteins, and apolipoproteins on vascular and nonvascular
mortality in the elderly. Arterioscler Thromb Vasc
Biol1997; 17:1224-32. [Full
Text]
P, Frishman WH, Ooi WL, Derman MP, Aronson M, Gidez LI, Eder HA. Plasma
lipids and lipoproteins and the incidence of cardiovascular disease in the
very elderly. The Bronx aging study. Arterioscl Thromb1992; 12:
416-423. [Pub
Med]
LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, Robbins JA,
Gardin JM. Risk factors for
5-year mortality in older adults: the Cardiovascular Health Study. JAMA
1998; 279:585-92.
[PubMed]
PH, Eaker ED.Serum cholesterol concentrations and
all-cause mortality in older people. Age Ageing 2000; 29:69-74. [Full
Text]
B, Tortrat D, Wolmark Y. Cholesterol as risk factor for mortality in elderly
women.Lancet
1989; 1:868-70. [Pub
Med]
AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total
cholesterol and risk of mortality in the oldest old. Lancet 1997;
350:1119-23. [PubMed]
A, Sigvaldason H, Sigfusson N. Total cholesterol and mortality after age 80
years. Lancet1997; 350:1778-9.
IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and
all-cause mortality in elderly people from the Honolulu Heart Program: a
cohort study.Lancet
2001; 358:351-5. [Pub
Med]
DB, Deev AD, Klimov AN, Davis CE, Tyroler HA. Increased risk of coronary
heart disease death in men with low total and low-density lipoprotein
cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study.
Circulation 1993; 88:846-53. [Pub
Med]
Competing interests:
None declared
Competing interests: No competing interests