The American Heart Association and the American Stroke Association
Content
The American Heart Association and the American Stroke Association
(AHA/ASA) released new Guidelines for the Primary Prevention of Stroke in
2014. This statement follows several other AHA statements released in 2013 on
general cardiovascular risk assessment, reducing the risks of cardiovascular
disease and stroke, including lifestyle management, treatment of blood
cholesterol, and the management of overweight and obesity.1-5 These new
statements are important for practicing physicians, clinical researchers and other
professionals, as well as patients, families, caregivers, policy makers and other
stakeholders invested in reducing the burden of stroke and health promotion.
Stroke continues to be a common and debilitating disease posing a major public
health problem. There have been encouraging positive trends in risk factor
control, stroke prevention and treatments in the last decade. Stroke mortality
declined from the 3rd leading cause of death to the 4th cause of death in the US. 6
Despite these advances, there is substantial ongoing regional and race-ethnic
disparities in stroke risk, incident stroke, received care, and outcomes.7 With
aging population, the global burden of stroke is likely to substantially increase
and therefore, implementation of effective primary stroke prevention strategies is
more important than ever. The real challenge, however, remains to successfully
implement evidence-based lifestyle and medical practices to the stroke
prevention programs and translate them to individuals.
New guidelines for the Primary Prevention of Stroke offer up-to-date
comprehensive evidence-based recommendations for the primary stroke
prevention, including the control of well-recognized risk factors such as
hypertension, atrial, diabetes, obesity, diet and lifestyle behaviors and less wellrecognized stoke risk factors including migraine, metabolic syndrome,
hyperhomocysteinemia, alcohol consumption, obstructive sleep apnea,
inflammation and infection, interventional approaches (e.g., asymptomatic carotid
stenosis) and antithrombotic treatments. Although these new guidelines follow
the format of the previous primary stroke prevention guidelines, recent
accumulated evidence for the importance of lifestyle and healthy behaviors as
well as genetics and pharmacogenomics in the stroke prevention has been
included, marking a trajectory for future individualized stroke prevention.
New guidelines for the Primary Prevention of Stroke take a shy, but nonetheless
important step towards personalized medicine. Personalized medicine with
patient-centered approach has emerged as a new strategy to prevention and
treatment of disease and will likely revolutionize the prevention and practice of
medicine. Individual patients become important partners in medical decisionmaking and take responsibility for their health. A “one size fits all” treatment
model has been recognized as potentially ineffective, while personalized
medicine offers the use of “tailored” approach to the prevention of disease. This
commentary highlights some of the important recommendations from new
guidelines for the Primary Prevention of Stroke with the potential for faster
transition to the personalized and more integrative prevention approaches.
Hypertension continues to be a major well-documented and modifiable risk factor
for stroke. Treatment of hypertension is the most effective strategy for stroke
prevention across all populations. However, optimal blood pressure (BP) targets
are still intensely debated. Lowering BP is strongly associated with reduction of
stroke risk, but reduction of BP to lower targets may not be beneficial in all
groups of individuals, such as in patients with diabetes or in the very elderly. The
2014 Primary Prevention of Stroke guidelines rely on the Joint National
Committee 7 (JNC-7) report, which was less controversial than the recently
published JNC-8 recommendations8 that were not endorsed by other professional
organizations.9 In the JNC-8, a lack of definitive benefit from BP clinical trials
among older populations was used as a base to raise the systolic BP treatment
goal recommendation from 140 mmHg to 150 mmHg. Whether this was a good
reason for the JNC-8 panel to change the existing treatment goal of systolic BP
at 140 mmHg continues to be debated. Nevertheless, hypertension remains
undertreated and personalized approach to lifestyle changes and medical
therapy of hypertension is critical for successful stroke prevention. Personal
approach to treatment of hypertension based on pharmacogenomics is also on
horizon.
New stroke prevention guidelines offer individualized approach to lifestyle
modification including physical activity, diet and nutrition, smoking cessation,
obesity and dyslipidemia. Although evidence from clinical trials for reduction of
many of these factors is lacking in primary stroke prevention, evidence from
observational studies is convincingly strong to make recommendations for
routine physical activity, diet, smoking cessation (in combination with drug
therapy using nicotine replacement, bupropion or vareniclinefor for active
smokers) and weight loss to prevent stroke with a high level of
recommendations. Some of these risk factors have alarmingly increasing trends.
In the US, obesity has tripled for children and doubled for adults since 1980. 10
The prevalence of obesity in the US is 36% among adults and 17% among
children, with the highest rates in non-Hispanic Blacks (50%), followed by
Mexican-Americans (41%), then all Hispanics (39%).11 While there is strong
evidence that increased weight is associated with an increased stroke incidence,
there is no clear evidence that weight loss in isolation reduces the risk of stroke.
A reduction of sodium intake and increased intake of potassium to lower BP as
well as DASH and Mediterranean style diet is considered beneficial for stroke
prevention. In addition to lifestyle changes, treatment with statin to LDL
cholesterol goals from National Cholesterol Education Program Guidelines
(NCEP)12 is recommended for primary prevention of ischemic stroke in patients
with coronary heart disease or diabetes mellitus. However, the effectiveness of
medical treatment of low HDL cholesterol with niacin or fibric acid derivatives for
hypertriglyceridemia has not been firmly established. Individualized approach to
cholesterol targets and effectiveness of lifestyle changes as well as tolerance to
medical treatments is now recommended.
Atrial fibrillation (AFib) is a prevalent, potent, and treatable risk factor for ischemic
stroke. AFib is associated with 4 to 5-fold increased risk of ischemic stroke.13 The
widely used CHADS214 and the CHA2DS2-VASc15 schemes offer an
individualized prediction model for primary stroke prevention. However, the
optimal treatment, which balances benefits and risks for an individual patient
remains challenging. AFib is currently a rapidly changing field with considerable
improvements in our ability to predict risk of stroke and treatment-related
hemorrhage. In addition, a number of new effective therapies including novel oral
anticoagulants such as dabigatran, apixaban, rivaroxaban and edoxaban have
became available. The new Primary Prevention of Stroke guidelines emphasize
an individualized approach to the selection of AFib antithrombotic agent on the
basis of patient risk factors, risk for stroke and risk for intracranial hemorrhage,
tolerability, potential for drug interactions, cost and other clinical characteristics,
and increasingly important patient preference. Despite large improvements in
treatments of AFib and public awareness, anticoagulation for appropriate AFib
patients remains underutilized, particularly among the elderly with the highest
prevalence of AFib.
New guidelines for the Primary Prevention of Stroke recommend the use of
aspirin for prevention of cardiovascular disease as well as stroke for individuals
whose risk is sufficiently high (10-year risk grater than 10%) for the benefits to
outweigh the risks associated with aspirin therapy. In low risk individuals
however, aspirin is not recommended in the primary stroke prevention or in
people with diabetes and without other high-risk factors. However, little evidence
is available in support of the use of antiplatelet therapy for the primary stroke
prevention from relevant clinical trials. In addition, the complexity of risk factors
within an individual makes stroke risk estimation a challenging proposition.16
More research is needed for individualized approaches to the use of
antithrombotics for the primary stroke prevention.
Novel recommendations are provided for genetic and pharmacogenomic testing
in the primary stroke prevention. A positive family history of stroke as well as sexspecific risk depending on parental history of stroke is recognized as an
important risk factor for stroke. Knowledge of genetic of stroke and CVD has
markedly expanded in recent years. For instance common variants on
chromosome 9p21 adjacent to the tumor suppressor genes CDKN2A and
CDKN2B, have been associated with ischemic stroke and myocardial infarction. 17
Pharmacogenomics and personalizing medicine has the potential to improve the
safety and efficacy of primary stroke prevention therapies. One example is
genetic variability in cytochrome P450 2C9 gene (CYP2C9) and vitamin K oxide
reductase complex 1 (VKORC1), which pharmacogenomic guiding management
strategy resulted with less serious adverse events.18 These data have supported
the recommendation to consider a pharmacogenomic-guided management
strategy for initiating warfarin. With the rapid evolution of the genomic medicine it
is anticipated that in the near future we will be able to determine genetically
based disease susceptibility within individuals, families, and populations as
proposed in the recent AHA scientific statement on genetics for prevention and
treatment of CVD.19 However, studies have yet to prove that altering preventive
therapies based on individualized genotype leads to reduced stroke risk.
In any guidelines, evidence-based recommendations usually assign level of
evidence based on the results from multiple clinical trials, which in general have
specific inclusion criteria. The applicability of these results may be questionable
at the level of individual if a person does not fulfill eligibility criteria required in
clinical trials. Personalized medicine refers to the tailoring of medical treatment to
the characteristics of individual. This requires our ability to prevent disease
according to the individual susceptibility to disease. The conflict between
guideline-based medicine and personalized medicine mainly occurs when
considering withholding a treatment that is recommended or supported by the
guidelines which may not be beneficial for an individual.20 Balance between
patient centered medicine and evidence-based guideline practices can be
achieved as integrated approach to prevention and shared decision-making is
the pinnacle of individualized stroke prevention. Primary stroke prevention
remains the object of intense medical research. Based on updated information
provided in the 2014 guidelines for the Primary Prevention of Stroke, most
management strategies for stroke prevention should be individualized. Although
we are not there yet, these guidelines have made a closer step towards
personalized medicine, which soon will substantially transform our approaches to
the primary prevention of stroke.
(AHA/ASA) released new Guidelines for the Primary Prevention of Stroke in
2014. This statement follows several other AHA statements released in 2013 on
general cardiovascular risk assessment, reducing the risks of cardiovascular
disease and stroke, including lifestyle management, treatment of blood
cholesterol, and the management of overweight and obesity.1-5 These new
statements are important for practicing physicians, clinical researchers and other
professionals, as well as patients, families, caregivers, policy makers and other
stakeholders invested in reducing the burden of stroke and health promotion.
Stroke continues to be a common and debilitating disease posing a major public
health problem. There have been encouraging positive trends in risk factor
control, stroke prevention and treatments in the last decade. Stroke mortality
declined from the 3rd leading cause of death to the 4th cause of death in the US. 6
Despite these advances, there is substantial ongoing regional and race-ethnic
disparities in stroke risk, incident stroke, received care, and outcomes.7 With
aging population, the global burden of stroke is likely to substantially increase
and therefore, implementation of effective primary stroke prevention strategies is
more important than ever. The real challenge, however, remains to successfully
implement evidence-based lifestyle and medical practices to the stroke
prevention programs and translate them to individuals.
New guidelines for the Primary Prevention of Stroke offer up-to-date
comprehensive evidence-based recommendations for the primary stroke
prevention, including the control of well-recognized risk factors such as
hypertension, atrial, diabetes, obesity, diet and lifestyle behaviors and less wellrecognized stoke risk factors including migraine, metabolic syndrome,
hyperhomocysteinemia, alcohol consumption, obstructive sleep apnea,
inflammation and infection, interventional approaches (e.g., asymptomatic carotid
stenosis) and antithrombotic treatments. Although these new guidelines follow
the format of the previous primary stroke prevention guidelines, recent
accumulated evidence for the importance of lifestyle and healthy behaviors as
well as genetics and pharmacogenomics in the stroke prevention has been
included, marking a trajectory for future individualized stroke prevention.
New guidelines for the Primary Prevention of Stroke take a shy, but nonetheless
important step towards personalized medicine. Personalized medicine with
patient-centered approach has emerged as a new strategy to prevention and
treatment of disease and will likely revolutionize the prevention and practice of
medicine. Individual patients become important partners in medical decisionmaking and take responsibility for their health. A “one size fits all” treatment
model has been recognized as potentially ineffective, while personalized
medicine offers the use of “tailored” approach to the prevention of disease. This
commentary highlights some of the important recommendations from new
guidelines for the Primary Prevention of Stroke with the potential for faster
transition to the personalized and more integrative prevention approaches.
Hypertension continues to be a major well-documented and modifiable risk factor
for stroke. Treatment of hypertension is the most effective strategy for stroke
prevention across all populations. However, optimal blood pressure (BP) targets
are still intensely debated. Lowering BP is strongly associated with reduction of
stroke risk, but reduction of BP to lower targets may not be beneficial in all
groups of individuals, such as in patients with diabetes or in the very elderly. The
2014 Primary Prevention of Stroke guidelines rely on the Joint National
Committee 7 (JNC-7) report, which was less controversial than the recently
published JNC-8 recommendations8 that were not endorsed by other professional
organizations.9 In the JNC-8, a lack of definitive benefit from BP clinical trials
among older populations was used as a base to raise the systolic BP treatment
goal recommendation from 140 mmHg to 150 mmHg. Whether this was a good
reason for the JNC-8 panel to change the existing treatment goal of systolic BP
at 140 mmHg continues to be debated. Nevertheless, hypertension remains
undertreated and personalized approach to lifestyle changes and medical
therapy of hypertension is critical for successful stroke prevention. Personal
approach to treatment of hypertension based on pharmacogenomics is also on
horizon.
New stroke prevention guidelines offer individualized approach to lifestyle
modification including physical activity, diet and nutrition, smoking cessation,
obesity and dyslipidemia. Although evidence from clinical trials for reduction of
many of these factors is lacking in primary stroke prevention, evidence from
observational studies is convincingly strong to make recommendations for
routine physical activity, diet, smoking cessation (in combination with drug
therapy using nicotine replacement, bupropion or vareniclinefor for active
smokers) and weight loss to prevent stroke with a high level of
recommendations. Some of these risk factors have alarmingly increasing trends.
In the US, obesity has tripled for children and doubled for adults since 1980. 10
The prevalence of obesity in the US is 36% among adults and 17% among
children, with the highest rates in non-Hispanic Blacks (50%), followed by
Mexican-Americans (41%), then all Hispanics (39%).11 While there is strong
evidence that increased weight is associated with an increased stroke incidence,
there is no clear evidence that weight loss in isolation reduces the risk of stroke.
A reduction of sodium intake and increased intake of potassium to lower BP as
well as DASH and Mediterranean style diet is considered beneficial for stroke
prevention. In addition to lifestyle changes, treatment with statin to LDL
cholesterol goals from National Cholesterol Education Program Guidelines
(NCEP)12 is recommended for primary prevention of ischemic stroke in patients
with coronary heart disease or diabetes mellitus. However, the effectiveness of
medical treatment of low HDL cholesterol with niacin or fibric acid derivatives for
hypertriglyceridemia has not been firmly established. Individualized approach to
cholesterol targets and effectiveness of lifestyle changes as well as tolerance to
medical treatments is now recommended.
Atrial fibrillation (AFib) is a prevalent, potent, and treatable risk factor for ischemic
stroke. AFib is associated with 4 to 5-fold increased risk of ischemic stroke.13 The
widely used CHADS214 and the CHA2DS2-VASc15 schemes offer an
individualized prediction model for primary stroke prevention. However, the
optimal treatment, which balances benefits and risks for an individual patient
remains challenging. AFib is currently a rapidly changing field with considerable
improvements in our ability to predict risk of stroke and treatment-related
hemorrhage. In addition, a number of new effective therapies including novel oral
anticoagulants such as dabigatran, apixaban, rivaroxaban and edoxaban have
became available. The new Primary Prevention of Stroke guidelines emphasize
an individualized approach to the selection of AFib antithrombotic agent on the
basis of patient risk factors, risk for stroke and risk for intracranial hemorrhage,
tolerability, potential for drug interactions, cost and other clinical characteristics,
and increasingly important patient preference. Despite large improvements in
treatments of AFib and public awareness, anticoagulation for appropriate AFib
patients remains underutilized, particularly among the elderly with the highest
prevalence of AFib.
New guidelines for the Primary Prevention of Stroke recommend the use of
aspirin for prevention of cardiovascular disease as well as stroke for individuals
whose risk is sufficiently high (10-year risk grater than 10%) for the benefits to
outweigh the risks associated with aspirin therapy. In low risk individuals
however, aspirin is not recommended in the primary stroke prevention or in
people with diabetes and without other high-risk factors. However, little evidence
is available in support of the use of antiplatelet therapy for the primary stroke
prevention from relevant clinical trials. In addition, the complexity of risk factors
within an individual makes stroke risk estimation a challenging proposition.16
More research is needed for individualized approaches to the use of
antithrombotics for the primary stroke prevention.
Novel recommendations are provided for genetic and pharmacogenomic testing
in the primary stroke prevention. A positive family history of stroke as well as sexspecific risk depending on parental history of stroke is recognized as an
important risk factor for stroke. Knowledge of genetic of stroke and CVD has
markedly expanded in recent years. For instance common variants on
chromosome 9p21 adjacent to the tumor suppressor genes CDKN2A and
CDKN2B, have been associated with ischemic stroke and myocardial infarction. 17
Pharmacogenomics and personalizing medicine has the potential to improve the
safety and efficacy of primary stroke prevention therapies. One example is
genetic variability in cytochrome P450 2C9 gene (CYP2C9) and vitamin K oxide
reductase complex 1 (VKORC1), which pharmacogenomic guiding management
strategy resulted with less serious adverse events.18 These data have supported
the recommendation to consider a pharmacogenomic-guided management
strategy for initiating warfarin. With the rapid evolution of the genomic medicine it
is anticipated that in the near future we will be able to determine genetically
based disease susceptibility within individuals, families, and populations as
proposed in the recent AHA scientific statement on genetics for prevention and
treatment of CVD.19 However, studies have yet to prove that altering preventive
therapies based on individualized genotype leads to reduced stroke risk.
In any guidelines, evidence-based recommendations usually assign level of
evidence based on the results from multiple clinical trials, which in general have
specific inclusion criteria. The applicability of these results may be questionable
at the level of individual if a person does not fulfill eligibility criteria required in
clinical trials. Personalized medicine refers to the tailoring of medical treatment to
the characteristics of individual. This requires our ability to prevent disease
according to the individual susceptibility to disease. The conflict between
guideline-based medicine and personalized medicine mainly occurs when
considering withholding a treatment that is recommended or supported by the
guidelines which may not be beneficial for an individual.20 Balance between
patient centered medicine and evidence-based guideline practices can be
achieved as integrated approach to prevention and shared decision-making is
the pinnacle of individualized stroke prevention. Primary stroke prevention
remains the object of intense medical research. Based on updated information
provided in the 2014 guidelines for the Primary Prevention of Stroke, most
management strategies for stroke prevention should be individualized. Although
we are not there yet, these guidelines have made a closer step towards
personalized medicine, which soon will substantially transform our approaches to
the primary prevention of stroke.
