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Cardiology:
Resources
Anticoagulation
Atrial Fibrillation
Cholesterol (High Lipids)
Congestive Hear Failure
Hypertension
Mitral Valve Prolapse
Varicose Veins (VV)
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Cardiology
Topics
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Lp(a)
Lipoprotein and Cardiovascular Risk:
The HOPE, PROGRESS and, more recently,
EUROPA studies have examined the effects of preventive
treatment with ACE inhibitors in normotensive high-risk
patients. In the HOPE study, patients with CHD, peripheral
vascular disease, stroke, or diabetes
(types 1 or 2) and an additional risk factor were randomly
allocated to receive ramipril 10mg daily or placebo.
Patients were included
irrespective of a history of hypertension, but those
with blood pressure greater than 140/90mmHg or with
a specific indication
for treatment with an ACE inhibitor (eg, CCF) were excluded.
The 3/1mmHg lower blood pressure in the ramipril group
at the end of
the study was unlikely to explain the highly significant
22%. reduction in the combined endpoint of cardiovascular
death, stroke
or heart attack (cardiovascular death [26% reduction;
ARR, 2.0%], stroke [32% reduction; ARR, 1.5%], heart
attack [20% reduction; ARR, 2.2%]; P < 0.05) or the
17% decrease in total mortality (P < 0.05).1
In the PROGRESS study,2 patients with a previous history
of stroke or TIA were randomly allocated to perindopril
4mg ± indapamide 2.5mg versus placebo, whether
there was a history of hypertension or not. When given
together this combination reduced the risk of recurrent
stroke (fatal or non-fatal) and major vascular events
in both normotensive and hypertensive patients with
this background.2 There was also a significant reduction
in major coronary events (26%) and the development of
heart failure (26%) in these patients with underlying
cerebrovascular disease.17 The magnitude of blood pressure
reduction in the active treatment group was greater
in the PROGRESS study (9/4mmHg) than in the HOPE study
(3/1mmHg), making it less clear as to how much of the
benefit seen in the PROGRESS study was independent of
blood pressure reduction alone.
The recently published EUROPA study16 looked at patients
with known ischaemic heart disease, and participants
were randomly
allocated to receive perindopril 8mg or placebo, independent
of whether or not they had a history of hypertension.
At 5 years, there
was a significant 20% reduction in cardiovascular mortality,
infarction and cardiac arrest in patients who received
perindopril, with a
blood pressure difference of 5/2mmHg between the groups.
It appears that, in patients with a history of CHD or
cerebrovascular
disease, treatment with a high dose ramipril- or perindopril
based regimen will improve outcomes whether or not there
is a history of hypertension, and that at least some
of these benefits are independent of blood pressure
reduction alone. In the immediate post-infarct management
of normotensive patients, a mortality benefit in the
short term has also been demonstrated with â-blockers18
and ACE inhibitors (particularly in patients with associated
heart failure),19 with less robust evidence for calcium
channel blockers, verapamil and diltiazem.20-22
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Lp(a)
Lipoprotein and Cardiovascular Risk:
Among older adults in the United
States, an elevated level of Lp(a)
lipoprotein is an independent predictor of stroke,
death from vascular disease, and death from any cause
in men but not in women. These data support the use
of Lp(a) lipoprotein levels in predicting the risk of
these events in older men (Ariyo et al., N Engl J Med
(2003): Lp(a)
Lipoprotein, Vascular Disease, and Mortality in the
Elderly).
However, Saely et al. (NEJM
Letter) suggest that the failure of the Ariyo
study to find Lp(a) predictive of coronary artery disease,
despite is status as an atherosclerotic and prothrombotic
risk factor may be that patients with established coronary
heart disease were excluded from the Ariyo study. In
an accompanying perspective, Angelo M. Scanu, MD, notes
that the risk associated with high Lp(a) lipoprotein
levels varies with genetic and environmental factors.
"High plasma levels of Lp(a) lipoprotein may have
different implications in different persons — a fact
that indicates the need to evaluate patients on an individual
basis," Dr. Scanu writes. "From the therapeutic standpoint,
until specific and safe agents with the capacity to
lower the plasma levels of Lp(a) lipoprotein are identified,
the focus should be on the correctable factors. For
example, in patients with hypertriglyceridemia, niacin
may be beneficial in effecting a shift in Lp(a) lipoprotein
from the small, dense particles to the relatively benign,
large particles, along with a parallel shift within
the class of LDL."
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Optimal
INR:
Several recent findings have critically clarified the
optimal range of anticoagulation required to avoid excess
mortality. A seminal study in BMJ, Oral
Anticoagulation and Risk of Death (click
to read), concludes (1) that a
narrower therapeutic window of INR between 2.2 - 2.3
is more optimal than that commonly used,
irrespective of treatment indication, and associated
with the lowest risk of death for all indications; and
(2) that more preventive actions need be taken to avoid
episodes of high INR. Evidencewatch believes this finding
should alter clinical practice and future evidence-based
guidelines for anticoagulation treatment. See the Evidencewatch
section on Anticoagulation
in our Cardiology
topic for this and further studies.
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Hawthorn
for (CHF) Chronic Heart Failure:
A recent meta-analysis (Pittler et al., Am J Med: Hawthorn
extract for treating chronic heart failure: meta-analysis
of randomized trials) of patients exhibiting
NYHA CFS classes I to III has found " . . .
a significant benefit from hawthorn extract as an adjunctive
treatment for chronic heart failure" (maximum
workload, pressure-heart rate product, dyspnea and fatigue
showed clinical benefit), with few, mild, and transient
adverse events). This confirms earlier studies of the
cardio-protective effect of Hawthrorn extract (Degenring
et al., Phytomedicine (2003): A
randomised double blind placebo controlled clinical
trial of a standardised extract of fresh Crataegus berries
(Crataegisan®) in the treatment of patients with
congestive heart failure NYHA II); and
Schröder et al., Eur J Heart Fail (2003):
Efficacy of a homeopathic Crataegus preparation compared
with usual therapy for mild (NYHA II) cardiac insufficiency:
results of an observational cohort study),
which concluded that hawthorn extract was non-inferior
to usual ACE inhibitor/diuretics treatment for mild
cardiac insufficiency on all parameters except BP reduction).
In addition, Habs (Forsch Komplementarmed Klass Naturheilkd
(2004): Prospective,
Comparative Cohort Studies and Their Contribution to
the Benefit Assessments of Therapeutic Options: Heart
Failure Treatment with and without Hawthorn Special
Extract WS 1442)
reports on the WISO cohort study (Efficacy and socio-economic
relevance of treatment of chronic heart failure stage
NYHA II with Crataegus extract WS® 1442) which compared
two different therapeutic strategies in the treatment
of heart failure stage NYHA II, i.e. a conventional
medication (the comparative cohort) and a therapy which
also includes hawthorn special extract in addition to
chemical-synthetic drugs (the
Crataegus cohort).
WS 1442 is a standardized extract (5:1) of hawthorn
leaves and flowers, standardized to contain 18.75% oligomeric
procyanidins (produced
by the Dr. Wilmar Schwabe Co., Karlsruhe, Germany).
The study found favourable effects on clinical symptoms
despite the fact that the patients in the Crataegus
cohort received markedly fewer chemical-synthetic drugs
than the patients in the comparative cohort (ACE-inhibitors:
36 vs. 54%, cardiac glycosides: 18 vs. 37%, diuretics:
49 vs. 61%, and beta-blockers: 22 vs. 33%), establishing
a clear benefit for patients with heart failure stage
NYHA II treated with hawthorn extract, with monotherpay
or addon administration in addition to a chemical-synthetic
medicationdemonstrating objective improvements at comparable
costs.
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Coenzyme
Q10 (CoQ10):
Evidencewatch notes that the anti-oxidant Coenzyme Q10
has also demonstrated efficay and benefit in cardiovascular
disease, especially hypertension, hyperlipidemia, coronary
artery disease, and heart failure (see the recent review:
Sarter, J Cardiovasc Nurs: Coenzyme
Q10 and cardiovascular disease),
confirming earlier findings (Wilburn et al. (J Clin
Hypertens (2004): The
Natural Treatment of Hypertension);
Tran et al. (Pharmacotherapy (2001): Role
of Coenzyme Q10 in Chronic Heart Failure, Angina, and
Hypertension)).
In addition, the AACE (American
Association of Clinical Endocrinologists) Nutrition
Guideines Task Force has recently issued their evidence-based
AACE
Medical Guidelines for the Clinical Use of Dietary Supplements
and Nutraceuticals [pdf]; or see the
National
Guideline Clearinghouse summary) and found
that "Coenzyme Q10 (COQ10)
has beneficial effects for mitochondrial disorders,
congestive heart failure (CHF), and ischemia-reperfusion
injury", although no persuasive research
findings to date support its use for hypertension. (The
same AACE Nutrition Guidelines Task Force has assessed
the amino acid carnitine, concluding that "trials of
carnitine used in the tratment of CHF are emerging and
appear encouraging . . . similar results have been noted
in the treatment of cardiac and peripheral vascular
ischemic disease").
Note that despite scattered wholly unproven warnings,
the literature, searched exhaustively across all major
medical databases in various languages, is devoid of
any evidence or published study re any clinical interaction
or interference between Hawthorn and/or CoQ10 and anticoagulants,
including warfarin/coumadin and the studies cited above
likewise found no clinical significant interaction.
Re hypertension, it is thought that CoQ10 may lower
blood pressure by correcting an endogenous provitamin
deficiency (Tran et al., Pharmacotherapy (2001): Role
of coenzyme Q10 in chronic heart failure, angina, and
hypertension; see also Burke et al.,
South Med J (2001): Randomized,
dou-ble-blind, placeo-controlled trial of coenzyme Q10
in isolated systolic hypertension).
Recently, Wilburn et al. (J Clin Hypertens (2004): The
Natural Treatment of Hypertension)
have sytematically appraised the literature on CoQ10
and hypertension, finding some significant evidence
for its blood pressure lowering benefits.
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Fatty
Acids:
(1) ALA: Alpha-linolenic Acid:
It has been determined that alpha-linolenic acid (ALA),
an essential fatty acids in human, like other n-3 fatty
acids from marine origin, may prevent cardiac arrhythmias
and sudden cardiac death. De Lorgeril & Salen (Nutr
Metab Cardiovasc Dis (2004): Alpha-linolenic
acid and coronary heart disease)
in a recent review concluded that epidemiological studies
and dietary trials in humans suggest that alpha-linolenic
acid is a major cardio-protective nutrient; major sources
of ALA are canola oil (and canola-oil based margarine),
nuts, ground linseeds and green leafy vegetables, with
the optimal dietary intake being approx. 2 g per day.
(2) Omega-3 Fatty Acids in the Prevention of Coronary
Heart Disease:
Evidence from epidemiologic studies and human intervention
trials supports a role for n-3 fatty acids in the prevention
of CHD. The role of n-3 fatty acids in the secondary
prevention of CHD is clearly supported by recent randomized
clinical trials including the GISSI Prevenzione Study
(Lancet (1999): Dietary
supplementation with n-3 polyunsaturated fatty acids
and vitamin E after myocardial infarction: results of
the GISSI-Prevenzione Trial)
and the Lyon Diet Heart Study (De Lorgeril et al., Circulation
(1999): Mediterranean
diet, traditional risk factors, and the rate of cardiovascular
complications after myocardial infarction).
In addition, Marchioli et al. (Circulation (2002): Early
Protection Against Sudden Death by n-3 Polyunsaturated
Fatty Acids After Myocardial Infarction: Time-Course
Analysis of the Results of the Gruppo Italiano per lo
Studio della Sopravvivenza nell’Infarto Miocardico
(GISSI)-Prevenzione)
concluded that the early effect of low-dose (1 g/daily)
n-3 PUFAs on total mortality and sudden death supports
the hypothesis of an antiarrhythmic effect; independently,
Singer and Wurth (Prostaglandins Leukot Essent Fatty
Acids (2004): Can n-3 PUFA reduce cardiac arrhythmias?
Results of a clinical trial) found confirmed an antiarrhythmic
action of n-3 PUFA . This is in substantial agreement
with the findings of the cardioprotective effects of
a Mediterranean diet (see the recent systematic review
of Panagiotakis et al., Med Sci Monit (2004):
Can
a Mediterranean diet moderate the development and clinical
progression of coronary heart disease? A systematic
review
[pdf]). In
sum, these studies clearly demonstrate a reduction in
sudden cardiac death, strongly suggesting an antiarrhythmic
effect, associated with optimal n-3 fatty acid consumption,
and hence "n-3 fatty acids should be considered
a new important adjunct to existing cardiovascular prevention
strategies" (Covington, Am Fam Physician (2004):
Omega-3 fatty acids),
in agreement with the work of Erkkilä et al., among
others (Am J Clin Nutr (2003): n-3
Fatty acids and 5-y risks of death and cardiovascular
disease events in patients with coronary artery disease)
who conclude that ALA, EPA, and DHA are nutritional
factors that could potentially reduce the risk of death
in patients with CAD".
The American Heart Association's latest recommendations
(American Heart Association Nutrition Committee: Fish
consumption, fish oil, omega-3 fatty acids, and cardiovascular
disease) are that patients without documented CHD should
eat at least two servings of fatty fish per week along
with other foods rich in omega-3 fatty acids, while
those with CHD should consume at least one daily meal
that includes a fatty fish, or in the alternative use
a daily fish oil supplement for a recommended level
of 0.9 g per day of EPA. Given that typical commercial
fish oil supplements of 1g contain 180 mg of EPA + 120
mg of DHA, it would require three 1g capsules daily
in divided doses to achieve the recommended dosage of
0.9g of omega-3 fatty acids. Note however that the treatment
of hypertriglyceridemia the effective dose is substantially
higher, at 2 to 4 g per day.
Given that low intakes or blood levels of (EPA (eicosapentaenoic
acid) + DHA
(docosahexaenoic
acid) are independently
associated with increased risk of death from coronary
heart disease (CHD), coupled with the fact that red
blood cell (RBC) fatty acid (FA) composition reflects
long-term intake of EPA + DHA, Harris
and von Schacky () have proposed that the RBC EPA +
DHA, we they call the Omega-3 Index, be considered a
new risk factor for death from CHD.
Warnings:
(1) The RCT study of Burr et al. (Eur J Clin Nutr 2003):
Lack
of benefit of dietary advice to men with angina: results
of a controlled trial)
found that men consuming oily fish (two portions per
week), and particularly those supplied with fish oil
capsules (three daily), had a higher risk of cardiac
death; they observe that this result is unexplained
and may arise fromother confounding factors and influences.
However, methodological problems arose in connection
with this trial: compliance was assessed only in a very
small subgroup, and the trial was interrupted; to date,
independent confirmation is lacking of an adverse effect
of such consumption, especially on angina.
(2) A second issue arises in connection with ALA: Brouwer
et al. (J Nutr (2004): Dietary
alpha-linolenic acid is associated with reduced risk
of fatal coronary heart disease, but increased prostate
cancer risk: a meta-analysis)
have found that epidemiologic studies show an increased
risk of prostate cancer in men with a high intake or
blood level of ALA.
(3) Landmark & Aursnes (Tidsskr Nor Laegeforen 2004):
Mercury,
fish, fish oil and the risk of cardiovascular disease)
haveconfirmed that fish intake is a major source of
exposure to mercury, and a high mercury content probably
inhibits the beneficial effects of omega-3 fatty acids
on the development of coronary artery disease.
(3)
Linolenic Acid:
Although
it is known that dietary intake of linolenic acid is
associated with a decreased risk of cardiovascular disease
mortality, the mechanism for this benefit has been until
recently poorly understood. This
has now been clarifiied by Djoussé et al. (Am
J Clin Nutr (2003): Dietary
linolenic acid is inversely associated with plasma triacylglycerol:
the National Heart, Lung, and Blood Institute Family
Heart Study)
where it was found that total linolenic acid
consumption is
inversely related to plasma triacylglycerol concentrations,
suggesting this effect as the critical pathway for the
reduction of cardiovascular disease risk.
Consumer
Information:
ConsumerLab recently issued a detailed evaluation of
fatty acids from the consumer (products, brands, layman-orientation)
perspective (ConsumerLab (2004): Omega-3
Fatty Acids (EPA and DHA) from Fish/Marine Oils).
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Statins
and Stroke Prevention:
Briel et al. (Am J Med (2004): Effects
of statins on stroke prevention in patients with and
without coronary heart disease: A meta-analysis of randomized
controlled trials)
examined whether lipid-lowering interventions using
statins (also studied were fibrates, resins, n-3 fatty
acids, diet) prevent nonfatal and fatal strokes in patients,
with and without coronary heart disease, concluding
in their meta-analysis that statins reduce the incidence
of stroke in patients both in the presence and absence
of coronary heart disease.
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L-Arginine
and Congestive Heart Failure:
Bednarz et al. (Kardiol Pol (2004): L-arginine
supplementation prolongs duration of exercise in congestive
heart failure)
found that in patients with chronic stable CHF, supplementation
with moderate dose of L-arginine () prolongs exercise
duration, probably due to peripheral vasodilation, unloading
the heart and improved perfusion of working muscles.
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Herbal/Warfarin
Interaction:
Correcting the Record: Recently there have been several
scattered incidents purported to demonstrate a clinically
significant interaction between warfarin treatment and
various herbals, among them the anti-oxidant Coenzyme
Q10 (CoQ10) and
Ginkgo biloba. However,
a recent study (Engelsen et al., Ugeskr Laeger: Effect
of Coenzyme Q10 and Ginkgo biloba on warfarin dosage
in patients on long-term warfarin treatment. A randomized,
double-blind, placebo-controlled cross-over trial)
has found that Coenzyme Q10
and Ginkgo biloba do not influence the clinical effect
of warfarin. However, St,
John's Wort (at a dose of 900mg/daily), in contrast,
has been shown to increase the metabolism of warfarin
through its action on the cytochrome P450 pathways,
leading to the lowering of the INR. P450 induction has
also been demonstrated for diets rich in broccoli and
Brussels sprouts. Evidencewatch
notes however that many other claimed interactions between
anticoagulants and herbals are founded solely on anecdotal
single- or limited case reports, often lacking critical
detail to establish causal relationship.
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Heart
Watch: Evidence-based Treatment of Cardiovascular Disorders [updated:
8/03/2005]