Overview of primary prevention of coronary

heart disease and stroke

Author:
Charles H Hennekens, MD, DrPH
Section Editors:
David Seres, MD
Freek Verheugt, MD, FACC, FESC
Deputy Editors:
Jane Givens, MD
Brian C Downey, MD, FACC
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Mar 2019. | This topic last updated: Nov 27, 2018.

INTRODUCTION In the United States and most developed countries,

cardiovascular disease (CVD), which includes coronary heart disease (CHD),

stroke, and peripheral artery disease, is and will remain the leading cause of
death in men and women [1]. Further, CVD is becoming the leading cause of
death worldwide.

An overview of the primary prevention of CVD is presented here, including a

discussion of the additive benefits of risk factor reductions through therapeutic
lifestyle changes(TLCs) and adjunctive drug therapies of proven benefit.
Secondary prevention of CVD, emerging risk factors, and determining individual
risk of a patient without known CVD are discussed separately. (See "Overview
of the prevention of cardiovascular disease events in those with established
disease (secondary prevention) or at high risk" and "Overview of established
risk factors for cardiovascular disease" and "Cardiovascular disease risk
assessment for primary prevention: Our approach".)

RATIONALE The following have been identified as major risk factors

for cardiovascular disease (CVD), are modifiable, and should be considered for
intervention in all adults:
●Smoking
●Overweight and obesity
●Unhealthy diet
●Physical inactivity
●Dyslipidemia
●Hypertension
●Diabetes mellitus (considered in some guidelines as a coronary heart
disease [CHD] risk equivalent)

Globally, up to 90 percent of the stroke burden may be attributable to modifiable

risk factors, and up to 75 percent of this burden may be reduced by specifically
addressing lifestyle and metabolic risk factors. Additionally, in the descriptive
INTERHEART study of patients from 52 countries, nine potentially modifiable
factors accounted for over 90 percent of the population-attributable risk of a first
myocardial infarction (MI) [2,3]. These included cigarette smoking, dyslipidemia,
hypertension, diabetes, abdominal obesity, and psychosocial factors. In
addition, factors that were associated with lowered risks included regular
physical activity, daily consumption of fruits and vegetables, and daily
consumption of small amounts of alcohol. (See "Cardiovascular benefits and
risks of moderate alcohol consumption", section on 'Patients without known
CVD'.)

In descriptive data from a nationally representative survey, five modifiable risk

factors for CVD (elevated cholesterol, diabetes, hypertension, obesity, and
smoking) accounted for one-half of CVD deaths in United States adults aged 45
to 79 from 2009 to 2010 [4]. The preventable fraction of CVD mortality
associated with these risk factors was 54 percent for men and 50 percent for
women.

The deleterious consequences of multiple risk factors are, at least, additive. In

the Framingham Heart Study of over 5000 men and women, those with five risk
factors had a 10-year risk of a first CHD event of 25 to 30 percent, which is
comparable to the absolute risk of a recurrent event for many patients who have
survived a prior MI or occlusive stroke (figure 1) [5].

The majority of the risk factors for CVD and stroke are modifiable by preventive
measures, including both therapeutic lifestyle changes (TLCs) and adjunctive
drug therapies of proven benefit [6]. In the United States, since 1975, CVD
mortality has declined overall, although men and black people continue to
experience higher absolute mortality rates at earlier ages than their female and
white counterparts. However, since 2011, the rates of decline have slowed and
are no longer evident [7]. It has been estimated that nearly half of the decline is
due to earlier diagnosis and more aggressive treatment of modifiable risk
factors, especially of lipids and blood pressure with adjunctive drug therapies,
including statins, aspirin, angiotensin-converting enzyme (ACE) inhibitors, and
beta blockers [8]. The remaining half of the decline in CVD mortality is
attributable to favorable TLCs, such as avoidance and cessation of cigarette
smoking.

Further supporting the benefits of the primary prevention of CVD by maintaining

a healthy lifestyle was the Nurse's Health Study, a large, prospective cohort
study of over 120,000 female nurses followed for over 20 years. Women who
maintained a desirable body weight, ate a healthy diet, exercised regularly, and
did not smoke cigarettes experienced an 84 percent reduction in risk of clinical
CVD events [9]. Additionally, in the Women's Health Study of almost 40,000
female health professionals, practicing healthy lifestyle behaviors was
associated with a 55 percent lower risk of stroke [10].

MAJOR COMPONENTS
Healthy diet — Individuals who self-select for a healthy diet have significantly
lower risks of cardiovascular disease (CVD), including both coronary heart
disease (CHD) and stroke. Components of a healthy diet include intakes of:
●Fruits and vegetables
●Fiber, including cereals
●Foods with a low glycemic index and low glycemic load
●Monounsaturated fat rather than trans fatty acids or saturated fats
●Omega-3 fatty acids (from fish, plant sources, or supplements)
(see "Healthy diet in adults" and "Dietary carbohydrates" and "Dietary
fat" and "Fish oil and marine omega-3 fatty acids")

Observational studies have consistently shown that individuals consuming diets

high in vegetables and fruits, such as the Mediterranean diet, have a reduced
risk of CVD [11]. It is possible that the apparent benefit may be due to specific
compounds in vegetables and fruits. It is also likely that people who eat more
vegetables and fruits tend to eat less meat and saturated fat. (See "Healthy diet
in adults", section on 'Mediterranean diet'.)

Basic research has suggested mechanisms of benefit, and observational

studies have shown that individuals who self-select for diets high in antioxidant
vitamins or supplements have lower risks. Nonetheless, the most reliable data
from large-scale randomized trials have not shown significant benefits of
antioxidant vitamin supplementation in the primary prevention of CVD.
(See "Nutritional antioxidants in atherosclerotic cardiovascular
disease" and "Vitamin supplementation in disease prevention", section on
'Antioxidant vitamins'.)

The role of folic acid supplementation in patients at risk for CVD is discussed
separately.

Smoking avoidance and cessation — Cigarette smoking remains the leading

avoidable cause of premature death and a major avoidable cause of premature
disability. The totality of evidence indicates that the amount of cigarettes
currently smoked increases morbidity and mortality from CVD, and benefits of
cessation begin to appear after only a few months and reach that of the
nonsmoker in several years, even among older adults [12]. Thus, for CVD, it is
never too late to quit, whereas for cancer it is never too early, as the risks relate
largely to duration rather than amount currently smoked. (See "Overview of
smoking cessation management in adults"and "Cardiovascular risk of smoking
and benefits of smoking cessation" and "Secondhand smoke exposure: Effects
in adults".)

All smokers should be counseled on a regular basis to quit. A number of

approaches, including behavioral therapy, nicotine replacement therapy, and
other pharmacologic therapies, are available. (See "Overview of smoking
cessation management in adults".)

Hypertension control — Hypertension is a well-established risk factor for

CVD, including morbidity and mortality from stroke, CHD, heart failure, and
sudden death. (See "Cardiovascular risks of hypertension".)
 ●Definition – Hypertension is defined in the 2017 AHA/ACC guidelines
as a systolic pressure ≥130 mmHg or a diastolic pressure ≥80 mmHg
[13].
●Goal blood pressure – Goal blood pressure may depend in part upon
comorbidities (eg, diabetes, chronic kidney disease) and estimated
cardiovascular risk; these issues are presented separately.
(See "Goal blood pressure in adults with hypertension".)
●Nonpharmacologic measures – All patients with hypertension or
elevated blood pressure should practice nonpharmacologic TLCs
which include weight reduction if overweight or obese, salt restriction,
and avoidance of excess alcohol intake. (See "Overview of
hypertension in adults", section on 'Nonpharmacologic therapy'.)
●Pharmacologic therapy – Antihypertensive drugs are necessary for
patients with persistent hypertension despite TLCs. Most patients will
require multiple antihypertensive drug therapies to achieve their blood
pressure goal. The choice of a specific agent for hypertension is
presented separately. (See "Choice of drug therapy in primary
(essential) hypertension".)

Dyslipidemia — Several large-scale randomized trials and their meta-analyses

of statins in high-, moderate-, and low-risk primary prevention subjects without
clinical evidence of CHD have demonstrated clinical benefits on CVD, including
myocardial infarction (MI), stroke, and CVD death as well as total mortality [14].

Deciding who should be screened for dyslipidemia may vary based on different
guidelines. This issue is discussed in detail separately. (See "Screening for lipid
disorders in adults".)

All primary prevention subjects, especially those with dyslipidemia, should be

counseled to achieve and maintain a desirable body weight, engage in regular
physical activity, and eat a prudent diet. Deciding when statin treatment should
be initiated and the choice of adjunctive pharmacologic therapy of lipid
disorders in primary prevention of CVD are discussed in detail separately.
(See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in
primary prevention of cardiovascular disease".)

Physical activity — A number of observational studies have shown that

individuals who self-select for increased physical activity have lower morbidity
and mortality from CHD (figure 2).

Regular physical activity is recommended in the early school years and

throughout life. Common recommendations include moderate-intensity exercise
for 150 minutes a week, vigorous-intensity exercise for 75 minutes a week, or
an equivalent combination of these activities. Adults with limited exercise
capacity due to comorbidities should stay as physically active as their condition
allows [15,16]. Even modest amounts of regular physical activity, such as brisk
walking for 20 minutes daily, are associated with significant benefits on risk of
CHD [17]. Nonetheless, perhaps less than 20 percent of United States adults
achieve this level of daily activity [15,16].
The role of increased physical activity for primary prevention is discussed in
detail separately. (See "Exercise and fitness in the prevention of atherosclerotic
cardiovascular disease".)

Weight loss — In the United States and worldwide, overweight and obesity are
overtaking cigarettes as the leading modifiable cause of premature deaths [18].
Overweight and obesity increase risk for several major risk factors for CVD,
including hypertension, dyslipidemia, and insulin resistance, while weight loss
has been shown to improve these parameters [19-21]. Data from large
prospective cohort studies have consistently shown that individuals with higher
body weights have a linear increase in morbidity and mortality from CHD, after
appropriate adjustment for smoking and other confounders. (See "Overweight
and obesity in adults: Health consequences".)

In addition, in data from a random sample of the United States population from
the National Center for Health Statistics, over 40 percent of adults aged 40 and
over have metabolic syndrome, which is defined by the presence of three or
more of the following: abdominal obesity, hypertriglycerides ≥150 mg/dL, high-
density lipoprotein (HDL) <40 mg/dL in men or <50 mg/dL in women, systolic
blood pressure ≥130 mmHg or diastolic blood pressure ≥85, fasting glucose
≥100 mg/dL. These individuals have a 10-year risk of a first CHD event of 16 to
18 percent, which is as high as many individuals who have already had an MI or
stroke [22]. Such high-risk primary prevention subjects should be considered for
pharmacologic or surgical therapeutic options [23].

Selection of treatment for overweight subjects is based upon an initial risk

assessment. All should be evaluated for their willingness and ability to adopt
therapeutic lifestyle changes as well as other interventions of proven benefit. All
individuals who are willing, ready, and able to lose weight should receive
information about behavior modification, diet, and increased physical activity.
(See "Obesity in adults: Prevalence, screening, and evaluation" and "Obesity in
adults: Overview of management", section on 'Morbidity' and "Obesity in adults:
Overview of management", section on 'Mortality'.)

Management of type 2 diabetes — There is a pandemic of type 2 diabetes,

which is strongly associated with overweight and obesity. Morbidity and
mortality from diabetes includes both macrovascular (CHD, stroke, and
peripheral artery disease) as well as microvascular complications (retinopathy,
nephropathy, and neuropathy).

To reduce macrovascular complications, multifactorial interventions are crucial,

especially weight reduction, increased physical activity, and control of blood
pressure, lipids, and glucose [24]. (See "Overview of medical care in adults with
diabetes mellitus" and "Treatment of hypertension in patients with diabetes
mellitus".)

For microvascular complications, tight glycemic control reduces microvascular

complications in both type 1 and type 2 diabetes mellitus. Tight glycemic control
may also reduce risks of macrovascular complications in patients with type 1
and type 2 diabetes mellitus. The target A1C levels in patients with diabetes
should be tailored to the individual by weighing the benefits on morbidity and
mortality against the risk of hypoglycemia. Details of glycemic control in patients
with diabetes are discussed separately. (See "Glycemic control and vascular
complications in type 1 diabetes mellitus" and "Glycemic control and vascular
complications in type 2 diabetes mellitus".)

Aspirin — In primary prevention trials of individuals at low absolute risk of a

first CHD event, aspirin confers a statistically significant and clinically important
reduction in risk of non-fatal MI but no benefit on all-cause mortality and non-
fatal stroke [25]. The decision to recommend aspirin should be based upon an
individual clinical judgment that includes an assessment of the magnitude of
both the absolute CVD risk reduction and the absolute increase in major
bleeding. Aspirin use for primary prevention of CVD is discussed in more detail
separately. (See "Aspirin in the primary prevention of cardiovascular disease
and cancer", section on 'Potential benefits'.)

Benefits and risks of small amounts of daily alcohol — In numerous case-

control and prospective cohort studies, individuals who consume small amounts
of alcohol have lower risks of morbidity and mortality from CHD than
nondrinkers. The benefit seems related to the small amount of alcohol
consumed rather than the type of alcoholic beverage. In some, but not the
majority of analytic studies, individuals who consume red wine tend to have
lower risks than those who consume other types of alcohol. This inconsistent
finding may be due to other components in red wine or confounding by social
class. A meta-analysis of nearly 600,000 individuals in 83 prospective studies
who consumed alcohol found the lowest risk of all-cause mortality occurred at
alcohol intake of about 100 grams/week (approximately six drinks/week) [26]. In
this analysis, small amounts of daily alcohol intake were associated with a
decreased risk of mortality from myocardial infarction but not from other causes.
Thus, any benefit of daily alcohol intake for coronary artery disease must be
weighed against the risks, which include hypertension, cerebral hemorrhage,
and breast cancer. (See "Overview of the risks and benefits of alcohol
consumption" and "Cardiovascular benefits and risks of moderate alcohol
consumption".)

ADDITIVE BENEFITS OF MULTIPLE RISK FACTOR

REDUCTIONS
Lifestyle changes — In primary prevention, modification of multiple major risk
factors will produce additive reductions in risk of coronary heart disease (CHD)
and stroke [27].

A European prospective cohort study of 2339, including 1507 men and 832
women aged 70 to 90 without cardiovascular disease (CVD) or cancer at
baseline, assessed whether self-selection for a Mediterranean diet, being
physically active, having small to moderate alcohol intake daily, and/or not
smoking reduced all-cause and cause-specific mortality [28]. After a mean
follow-up of 10 years, compared with those who adopted zero or one lifestyle
change, those who self-selected for all four therapeutic lifestyle changes had a
67 percent lower risk of CVD mortality and a 65 percent lower risk of total
mortality.
A prospective cohort study of over 20,000 Swedish men aged 45 to 79 without
cancer, CVD, or CVD risk factors assessed whether individuals who self-
selected for all of the five low-risk factors (healthy diet, moderate alcohol
consumption, not smoking, being physically active, and having no abdominal
adiposity) had lower risks of myocardial infarction (MI) [29]. During 11-year
follow-up, these men who practiced a healthy lifestyle had an 86 percent lower
risk for MI (95% CI 0.04-0.43).

Similar results for primary prevention of stroke were seen in combined data
from two large prospective cohorts, the Health Professionals Follow-up Study
(43,685 men) and Nurses' Health Study (71,243 women), in which a low-risk
lifestyle was defined as not smoking, body mass index (BMI) <25 kg/m2, ≥30
minutes per day of moderate activity, modest alcohol consumption, and scoring
in the top 40 percent on a healthy diet score [30]. Compared with participants
having none, men and women with all five low-risk factors had significantly
lower risks of stroke (relative risks 0.31 in men and 0.21 in women).

Polypill — Polypills, containing various combinations of statins,

antihypertensive medications, and aspirin, have been developed to reduce CVD
risk [31]. Potential advantages of polypills include increased compliance and
decreased costs [32]. Potential disadvantages include increased adverse
effects, uncertainty of the "ideal" combination of medications, and difficulty in
titration. Polypills are investigational, although several different polypills are
available in India.

A systematic review of 13 randomized trials concluded that the effects of

polypills on mortality or CVD events are inconclusive, perhaps because most of
the included trials evaluated changes in CVD risk factors rather than CVD
events [33]. In some but not all individual randomized trials, polypills have been
associated with increased adherence and decreases in blood pressure and
cholesterol but increased adverse events [34-36].