Running head: PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIC SURGERY 1
Preoperative use of beta blockers in noncardiac surgery
Angela Robinson
Wright State University
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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Preoperative use of beta blockers in noncardiac surgery
Introduction
The purpose of this paper is to review recent literature and pertinent guidelines regarding
the use of beta blockers preoperatively in non-cardiac surgeries to reduce cardiovascular events.
Each year more than 230 million people undergo a noncardiac surgical procedure (Anderson et
al., 2014). Cardiovascular events occur in approximately two percent of these individuals,
resulting in substantial cardiac complications or myocardial damage (Anderson et al., 2014).
Understanding the potential cardiovascular complications is crucial during the preoperative
phase to conclude a risk index (low, intermediate or high) depending upon their history, physical,
age, and cardiac risk factors. Surgery increases the amount of stress hormones, which can linger
for several days, which increases the risk of undesirable postoperative cardiovascular events
(Anderson et al., 2014). Adverse effects associated with noncardiac surgical procedures include
myocardial infarction/ischemia, arrhythmias, and or death. Evidence-based research validates
the reduction of cardiovascular complications with the use of preoperative beta blockers in high
risk candidates. Thus, providers should be educated on the current guidelines of preoperative use
of beta blockers when determining the surgical risk level, to deem if benefits outweigh the risks.
Significance of Problem
It is estimated approximately 230 million people undergo a noncardiac surgical procedure
each year (Anderson et al., 2014). These individuals are at considerable risk of cardiovascular
morbidity and mortality up to 1.5% related to the physiological stressors one endures
(Poldermans, Hoeks, & Feringa, 2008). “Sudden cardiac deaths account for 300,000-400,000
deaths a year in the United States” (Al-Gobari, Khatib, Pillon, & Gueyffier, 2013, p. 1). Sudden
cardiac death is defined as a “restriction to death less than two hours from the onset of
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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symptoms” (Al-Gobari et al., 2013, p. 1). Cardiovascular complications is primarily manifested
by underlying coronary heart disease and accounts for 50% mortality rates in the United States
(Al-Gobari et al., 2013). Additional cardiovascular concerns postoperatively include lifethreatening arrhythmias and myocardial ischemia (Chopra, Plaisance, Cavusoglu, Flanders, &
Eagle, 2009).
Following a surgery, the body’s protective physiologic responses are activated under a
stressful event and heighten the risk of undesirable cardiovascular events, especially if
underlying disease is present (Chopra et al., 2009). The physiologic responses are crucial
perioperative factors that require consideration preceding noncardiac surgery. Prior to a surgical
procedure, the patient is evaluated with a cardiac risk index to determine the probability of an
adverse cardiac event (Poldermans et al., 2008). Goldman et al “developed the first
multifactorial cardiac risk index specifically for cardiac complications” (1977, p. 1914).
Subsequently, the risk assessment for noncardiac surgical patients has been revised and modified
to incorporate the pertinent multifactorial risk factors, “the most common one used is the
Revised Cardiac Risk Index (RCRI)” (Poldermans et al., 2008, p. 1914). The RCRI determines
the risk factors based on “high-risk surgery (intrathoracic, intra-abdominal, or vascular),
Ischemic heart disease (history of myocardial infarction, pathologic Q wave on ECG, use of
nitrate, abnormal stress test, or chest pain secondary to ischemic causes), congestive heart
failure, history of cerebrovascular disease, diabetes mellitus requiring insulin therapy, and
preoperative serum creatinine level greater than 2 mg/dL” (Grasso & Jaber, 2014, p. 1). Once a
risk index is determined, specific guideline class grades are recommended.
The perioperative cardiovascular events that are worrisome include “hyper-coagulopathy,
decreased fibrinolytic activity, increased inflammatory responses, tachycardia, plaque rupture,
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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vasomotor reactivity, altered diastole, and coronary perfusion” (Chopra et al., 2009, p. 224). The
body releases a surge of catecholamine’s (dopamine, norepinephrine, and epinephrine) which
play a vital role in regulating heart rate, blood pressure, muscle tone, and glucose metabolism
(Marino, 2014). These specific high catecholamine’s can linger for remain for days creating a
life-threatening risk of disruption of vulnerable coronary plaque, thus increasing the risk for
cardiovascular events (Chopra et al., 2009).
Beta-blockers purposed benefits focus on the effect of “restoring oxygen
demand/mismatch by a decrease in heart rate, systolic pressure, ventricular contractility, and
reduction of blunting of the hypertensive response on intubation” (Chopra et al., 2009, p. 222).
“Beta-blockers receptor antagonists are separated into B1-selective and B2 –non-selective
adrenoreceptor blockers, however B1-selective are the beta-blockers used preoperatively”
(Poldermans et al., 2008, p. 1917). Prolong use of beta-blockers suggest the stabilization of
coronary plaque may be correlated to reduction of anti-inflammatory properties (cytokines)
(Poldermans et al., 2008). The American College of Cardiology Foundation and American Heart
Association guidelines recommend beta-blocker initiation or continually use if an individual
meets criteria for class I and IIa (Fleischmann et al., 2009). Class IIb may or may not be
reasonable, it depends on if the benefits outweigh the risks. Class III is not recommended due to
the potential harmful risks associated with the use of beta-blockers (nonfatal stroke or
hypotension) (Fleischmann et al., 2009). Research supports the use of beta-blockers in people
with high RCRI indicating the potential risk of a cardiovascular event (Anderson et al., 2014). In
a preoperative evaluation, beta-blocker therapy is recommended if a person is scheduled for a
high-risk surgery and who have greater than two clinical risk factors or an American Society of
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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Anesthesiologists (ASA) status of greater than three indicating severe systemic disease
(American Society of Anesthesiology, 2014).
Discussion of problem consequences
Initiation of beta-blockers is not recommended for individuals with an ASA I or II which
indicate a person is healthy or with mild systemic disease without functional limitations due to
the potential harmful effects (American Society of Anesthesiology, 2014). Beta-blocker therapy
is indicated in individuals with an ASA III, IV, V, VI, or E consistent with severe systemic
disease requiring an intervention (insulin, chest pain with exertion, unstable, or an emergent
surgery) (American Society of Anesthesiology, 2014). Although, beta-blocker therapy requires
tight heart rate regulation with a goal of 60-70 beats per minute to maintain a long diastole to
maximize circulation in restricted arteries (Foex & Sear, 2014). The preoperative use of betablockers evidence is consistent with significant adverse effects including hypotension and
bradycardia, which may require intervention (Mangano, Layug, Wallace, & Tateo, 1996). The
perioperative ischemia evaluation (POISE) trial suggested hypotension (Systolic blood pressure
less than 90 mmHg) an important correlation to perioperative cerebrovascular accidents
(Mangano et al., 1996). Although, cerebrovascular accidents is a high morbid unfavorable
outcome, they are less common when compared to major adverse cardiac events (MACE)
(Fleisher et al., 2014).
Treatment issues
There is relevant research conducted wide-spread with the administration of betablockade therapy, however, evolving research suggests risk analysis evaluation prior to
administration to ensure the benefits outweigh risks (Fleisher et al., 2014). The American
College of Cardiology (ACC)/ American Heart Association (AHA) guidelines 1996/2002
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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recommended the use of perioperative beta blockades in a variety surgical patients undergoing
noncardiac surgery (Anderson et al., 2014). However, further investigation identified concerns
with the strength and scope of these recommendations, which lead to updated guidelines based
reflect of current scientific data (Anderson et al., 2014). The overall principles have not
changed, but updated the clinical data to provide optimal patient outcomes (Freeman & Gibbons,
2009).
There is current evidence that supports the use of established beta-blockage, but
preexisting information must be interpreted with caution due to the broad spectrum beta blocker
regimen without specific titration protocol, route of administration, timeframe, and sample size
(Freeman & Gibbons, 2009). The current guidelines suggest appropriate administered betablockers dosed accordingly to sustain a target heart rate can reduce cardiovascular events, but is
limited in successfully excluding risk of surgical death (Fleisher et al., 2014). Evidence supports
the potential adverse outcomes with the use of beta-blockade therapy including stroke and
bradycardia, although, each clinical case requires a cardiovascular evaluation to determine their
risk index (Fleisher et al., 2014). The current literature recommendations include: “continual
chronic beta-blocker therapy (Class Ib evidence B), initiation of therapy based on clinical
decision, independent of when the agent was started (Class IIa evidence B), patients with
intermediate or high myocardial infarction based on preoperative risk index and or diagnostic
data (EKG/2D-Echocardiogram/Stress test) (Class IIb evidence C), patients with a compelling
long-term indication for beta-blocker therapy but no other RCRI factors to reduce perioperative
risk of uncertain benefit (Class IIb evidence level B), and initiation of beta-blockers in advance
to assess for safety and tolerability, preferably more than one day prior to surgery (Class IIb
evidence level B)” (Fleisher et al., 2014, p. 103). Up-to-date guidelines do not recommend beta-
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blocker therapy initiation of the day of the procedure due to the lack of monitoring for safety,
tolerability, and target heart rate (Class III harmful evidence level B) (Fleisher et al., 2014).
Concerns in the elderly
Advancement in surgical procedures and the type of anesthesia requirements in
correlation with a thorough preoperative evaluation have contributed to the increased number of
older adults (greater than 65 years old) undergoing noncardiac surgery (Ersan & Schwer, 2013).
Approximately 50% of older adults will undergo a surgical procedure when older than 65 years
(Ersan & Schwer, 2013). In order to minimize cardiovascular events, a perioperative evaluation
including a 12-lead electrocardiogram, cardiac biomarkers, comprehensive blood work,
pulmonary function test, and or echocardiogram/stress test depending on degree of disease
(Ersan & Schwer, 2013). Comorbid conditions contribute to the increased risk of the older adult
developing complications due to their limited functional capacity and slower recovery, which
increase the probability of death (Ersan & Schwer, 2013). Important factors to consider when
evaluating an older adult to determine their risk level includes age, functional capacity,
nutritional status, mental status, and support system. “Advanced age, poor functional status at
baseline, impaired cognition, and limited support at home are risk factors for adverse outcomes”
(Ersan & Schwer, 2013, p. 1). Severity of illness is a more reliable predictor when compared
with age, but an emergent procedure carries the greatest risk in any age, especially the elderly
(Ersan & Schwer, 2013).
As an AG-ACNP, it is important to complete a thorough history and physical with an upto-date list of medications. A low albumin “less than 3.2 g/dL and a cholesterol level of less than
160 mg/dL in frail hospitalized elderly people are highly predictive of subsequent mortality”
(Ersan & Schwer, 2013, p.1). Elderly people undergoing an elective surgery are at greatest risk
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for cardiovascular complications, especially if any recent or history of MI, uncompensated heart
failure, unstable heart disease, or arrhythmias (Ersan & Schwer, 2013). It is important to ensure
the proper precautions are taken to reduce postoperative complications. In the elderly
population, comorbid conditions can trigger rapid decline if not monitored properly with
diagnostic laboratory data, capnography, and telemetry if indicated. The older adults present
differently when compared to middle age adults, therefore, it is important to actively listen to
their concerns.
Relevant research
An extensive systemic literature review was conducted which included PubMed,
Cochrane Central Register of Controlled Trials, CENTRAL, EMBASE, and MEDLINE
databases (Anderson et al., 2014). The study selection and guidelines were according to
“Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) (Al-Gobari
et al., 2013, p. 2). The literature review selected included specific inclusion/exclusion criteria,
study design, and follow-up, and outcomes. The Jadad score was used to evaluated the quality of
the randomized control trials (Al-Gobari et al., 2013). In this meta-analysis, a total of 30 RCT’s
met the criteria with a known chronic heart failure– to be reviewed (n=24,779) patients. The
mean follow-up duration was 11.51 months with a Jadad score of three-five, consistent with high
quality (Al-Gobari et al., 2013). The results revealed “3,764 deaths occurred in the 24,779
patients included in this analysis, including 1597 sudden cardiac deaths 5.27% (n=673/12,768
treated with beta blockers) when compared to the placebo group 7.69% (n=924/12,011 in the
placebo/control group) (OR 0.69; 95% CI, 0.62-0.77, P <0.00001)” (Al-Gobari et al., 2013, p.6).
“All-cause mortality rate was 12.82% (n=626/12,678) in those treated with beta-blockers and
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17.80% (n=2138/12011) in these in the placebo/control group (OR 0.67; 95% CI, 0.59-0.76, P <
0.00001)” (Al-Gobari et al., 2013, p. 6).
In summary, the RCT’s were shown to be effective in reducing cardiovascular events.
Patients with known chronic cardiovascular disease with the continual use of “beta blocker use
reduced the risk of sudden cardiac death by 31%, cardiac death by 29%, and all-cause mortality
by 33%”, which identified positive outcomes, hence, recommending therapy for people with
chronic cardiac disorders (Al-Gobari et al., 2013, p. 7).
A Danish Nationwide Cohort Study to assess the correlation of beta blockage therapy in
reducing major cardiac adverse events (MACE) (Andersson et al., 2014). The inclusion criteria
required were individuals with ischemic heart disease with or without heart disease and
with/without history of MI undergoing a noncardiac surgery. The Adjusted Cox Model were
used to analyze the postoperative 30-day potential MACE (Ischemic stroke, MI, or
cardiovascular death) (Andersson et al., 2014). The participants n= 28,263 with history of
ischemic heart disease/heart failure n=7990 (28.3%) and without heart failure n= 20,273
(71.1%). Beta blocker were administered in 53.3% with heart failure and 36.6% without. The
results revealed a lower risk of MACE with use of beta blockers “(HR, 0.75; 95% CI, 0.70-0.87),
all-cause mortality (0.80; 0.70-0.92), whereas the patients without heart failure without beta
blocker use (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions)”
(Andersson et al., 2014, p. 336). In addition, the patients without heart failure, beta blockers
reduced the risk among those with a recent “MI (<2 years), with HR’s of 0.54 (95% CI, 0.370.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P <.02 for interactions between
beta blocker therapy and time period after MI)”, but no significance in the other individuals
(Andersson et al., 2014, p. 337).
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Several recognized studies were reviewed, “16 were RTC’s (n=12043) and one was a
cohort study (n=348) participants” (Anderson et al., 2014, p. 2407). Beside one RCTs, each
study administered beta blocker therapy less than one day prior to surgery. The results revealed
a decrease in “nonfatal MI (RR: 0.69, 95% CI, 0.58-0.82) but increased nonfatal stroke (RR:
1.76; 95% CI: 1.07-2.91), hypotension (RR: 0.69; 95% CI: 1.34-1.60), and bradycardia (RR:
2.61; 95% CI: 2.18-3.12)” (Anderson et al., 2014, p. 2407). Dutch Echocardiographic Cardiac
Risk Evaluation Applying Stress Echo (DECREASE) and POISE trials were excluded from this
study due to the mortality rate differed from other trials. The DECREASE trial with the use of
beta blockers revealed a decreased trend in all-cause mortality “(RR: 0.42; 95% CI: 0.15-1.22)
but with increased all-cause mortality in other trials (RR: 1.30; 95% CI: 1.03-1.64)” (Anderson
et al., 2014, p. 2407). “Beta blockers decreased cardiovascular mortality rate (RR: 0.17; 95%
CI: 0.05-0.64), but were associate with trends toward increased mortality rate in other trials (RR:
1.25; 95% CI: 0.92-1.17)” (Anderson et al., 2014, p. 2407). In conclusion, initiation of beta
blockers within 24 hours of a noncardiac surgery reduce the risk of MI, but increase the potential
for adverse events including stroke, hypotension, bradycardia, and death (Anderson et al., 2014).
More multicenter RCTs are recommended for the review of beta blocker use prior to one day of
a noncardiac surgery to address the gap (Anderson et al., 2014).
The POISE trial initiated randomized extended-release metoprolol achieving the
maximum dose of 400 mg within the day of an individual undergoing a noncardiac surgery
(Poldermans et al., 2008). The results of the trial revealed a reduction in perioperative MI, but
overall mortality was high and 1% risk of stroke when compared to the DECREASE trial 0.4%
(Poldermans et al., 2008). There were several concerns with the POISE trial including adverse
events such as stroke, hypotension, and bradycardia indicating the beta blocker dose was too
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high (Poldermans et al., 2008). The benefit of this trial could be with proper titration and
administration without abrupt discontinuation, may reduce risk of adverse events Poldermans et
al., 2008).
The current guidelines are based on several different reviews, which have been updated
accordingly based on scientific data that is proven by different levels of evidence to support
optimum delivery of care. The ACC/AHA classifications of evidence are based upon research
that supports the given procedure/therapy (Class I), conditions for which there conflicting
evidence is based on opinion, but weight is favorable/effective (Class IIa) established through
meta-analyses, effectiveness is less established by an opinion (Class IIb) evidence based on
randomized trial or nonrandomized studies, Class IIc are limited due to case studies or consensus
opinion of experts with limited population studies, or the evidence or agreement the
procedure/therapy may be cause harm (Class III) (Anderson et al., 2014).
Role of the Acute Care Nurse Practitioner in relation to the problem
The adult gerontological acute care nurse practitioner (AG-ACNP) with a current
certificate of authority/certificate to prescribe (CTP) may conduct preoperative evaluation and
prescribe beta-blockers if indicated (Ohio Board of Nursing, 2014). Evidence based practice
(EBP) guidelines is vital for the AG-ACNP to utilize within their daily clinical practice to ensure
the proper care is being delivered. The use of EBP allows the AG-ACNP to incorporate highquality current research which guides direction to promote optimal patient outcomes. Research
studies are always being conducted, therefore, it is important for AG-ACNP to remain current
and participate in continual education. AG-ACNP’s portray the leadership ability to educate
patients, families, staff, and providers. Based on the current research, beta-blockers should be
continued and if their RCRI or ASA warrants indication to reduce cardiovascular events.
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
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Conclusion
Beta blocker therapy preoperatively is a controversial topic due to evolution opinions.
The guidelines are specific, in regards, to individuals with a cardiovascular history or high risk of
developing an adverse event, which should be thoroughly evaluated. Each patient should be
evaluated individually with treatment directed in providing the best outcome. The World Health
Organization (WHO), indicates that cardiovascular disease will ultimately shift from developed
to developing countries, in which AG-ACNP’s will be crucial in providing evidence-based
research, leadership, and preventative measures to aid in reduction of adverse cardiovascular
events (2015). Multiple research studies have been conducted with high grade evidence
supporting the use of beta blockers in individuals that meet specific criteria. Given this
information, following the current guidelines can reduce length of stay, financial costs, overall
mortality, and promote optimal care outcomes.
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References
Al-Gobari, M., Khatib, C., Pillon, F., & Gueyffier, F. (2013). Beta-blockers for the prevention of
sudden cardiac death in heart failure patients: a meta-analysis of randomized controlled
trials. BMC Cardiovascular Disorders, 13(52), 1-9. http://dx.doi.org/10.1186/1471-226113-52
American Society of Anesthesiology. (2014). Retrieved from http://www.asahq.org
Anderson, J., Haloperin, J., Albert, N., Bozkurt, B., Brindis, R., Curtis, L., ... Fleisher, L. (2014).
Perioperative beta blockade in noncardiac surgery. A systematic review for the 2014
ACC/AHA guideline on perioperative cardiovascular evaluation and management of
patients undergoing noncardiac surgery. Journal of the American College of Cardiology,
64 (22), 2407-2425. http://dx.doi.org/10.1016/j.jacc.204.07.939
Andersson, C., Merie, C., Jorgensen, M., Gislason, G., Torp-Pedersen, C., Overgaard, C., ...
Jensen, P. (2014). Association of b-blocker therapy with risks of adverse cardiovascular
events and deaths in patients with ischemic heart disease undergoing noncardiac surgery.
JAMA Internal Medicine, 174 (3), 336-344.
http://dx.doi.org/10.1001/jamainternmed.2013.11349
Chopra, V., Plaisance, B., Cavusoglu, E., Flanders, S., & Eagle, K. (2009). Perioperative betablockers for major noncardiac surgery: primum non nocere. The American Journal of
Medicine, 122, 222-229. http://dx.doi.org/10.1016/j.amjmed.2008.1.004
Ersan, T., & Schwer, W. (2013). Perioperative management of the geriatric patient. , 1-8.
Retrieved from http://emedicine.medscape.com/article/285433-overview
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
14
Fleischmann, K., L., Beckman, J., Brown, K., Calkins, H., Chaikof, E., Fisher, L. ... Kasper, E.
(2009). 2009 ACCF/AHA Focused update on perioperative beta blockade. . Circulation,
2123-2151. http://dx.doi.org/10.1161/circulationaha.109.192689
Fleisher, L., Fleischmann, K., Auerbach, A., Barnason, S., Beckman, J., Bozkurt, B., ... GerhardHerman, M. (2014). 2014 ACC/AHA Guideline on perioperative cardiovascular
evaluation and management of patients undergoing noncardiac surgery. Journal of the
American College of Cardiology, 64 (22), 77-137.
http://dx.doi.org/10.1016/j.jacc.2014.07.944
Foex, P., & Sear, J. (2014). B-blocker and cardiac protection. Br J Anaesth, 112 (2), 206-210
Retrieved from http://www.medscape.com/viewarticle/819576_6
Freeman, W., & Gibbons, R. (2009). Perioperative cardiovascular assessment of patients
undergoing noncardiac surgery. Symposium on Cardiovascular Diseases, 84 (1), 79-90.
Retrieved from
Goldman, L., Calfdera, D., & Nussbaum, SR, et al. (1977). Multifactorial index of cardiac index
in noncardiac surgical procedures. N Engl J Med, 297, 845-850. Retrieved from
Grasso, A., & Jaber, W. (2014). Cardiac risk stratification for noncardiac surgery. Retrieved
from
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/cardi
ac-risk-stratification-for-noncardiac-surgery/
Mangano, D., Layug, E., Wallace, A., & Tateo, I. (1996). Effect of atenolol on mortality and
cardiovascular morbidity after noncardiac surgery. The New England Journal of
Medicine, 335 (23), 1713-1720. Retrieved from
PREOPERATIVE USE OF BETA BLOCKERS IN NONCARDIAC SURGERY
15
Marino, P. (2014). The ICU Book (4th Ed.). New York, New York: Wolters Kluwer
Health/Lippincott Williams and Wilkins.
Ohio Board of Nursing. (2014). Formulary with index for CTP holders. Retrieved from
http://www.nursing.ohio.gov/PDFS/AdvPractice/Formulary_9-22-2014_3.pdf
Poldermans, D., Hoeks, S., & Feringa, H. (2008). Pre-operative risk assessment and risk
reduction before surgery. Journal of the American College of Cardiology, 51 (20), 19131924. http://dx.doi.org/10.1016/j.jacc.2008.03.005
World Health Organization. (2015). Retrieved from
http://www.who.int/topics/cardiovascular_diseases/en/