Accepted Manuscript

Title: Prevalence and prevention of cardiovascular disease and

diabetes mellitus

Authors: Pitchai Balakumar Khin Maung-U Gowraganahalli

Jagadeesh PhD, Senior Expert Pharmacologist

PII: S1043-6618(16)30782-4
DOI: http://dx.doi.org/doi:10.1016/j.phrs.2016.09.040
Reference: YPHRS 3348

To appear in: Pharmacological Research

Received date: 12-8-2016

Revised date: 28-9-2016
Accepted date: 29-9-2016

Please cite this article as: Balakumar Pitchai, Maung-U Khin, Jagadeesh
Gowraganahalli.Prevalence and prevention of cardiovascular disease and diabetes
mellitus.Pharmacological Research http://dx.doi.org/10.1016/j.phrs.2016.09.040

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 Cardiovascular
risk factors

Non-modifiable risk Global partnership of Modifiable risk factors

factors nationwide public health
campaigns should be
organized to create
awareness among the
public with information
pertaining to the
Hypertension
primary prevention and
Tobacco use
management of CVDs
Diabetes mellitus
and diabetes mellitus.
Age Physical inactivity
Gender Obesity
Family history
X Unhealthy diet
Cholesterol and lipids
Depression and anxiety
Stress
 INVITED REVIEW

Prevalence and prevention of cardiovascular disease and diabetes mellitus

Pitchai Balakumar1, Khin Maung-U2,3, Gowraganahalli Jagadeesh2,3,*

1
Pharmacology Unit, Faculty of Pharmacy, AIMST University,
08100 Bedong, Kedah Darul Aman, Malaysia
2
Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research,
US Food and Drug Administration (FDA), Silver Spring, Maryland 20993, USA

*Correspondence:

Gowraganahalli Jagadeesh, PhD

Senior Expert Pharmacologist
Division of Cardiovascular and Renal Products
Office of Drug Evaluation I, Office of New Drugs
Center for Drug Evaluation and Research
US Food and Drug Administration (FDA)
10903 New Hampshire Avenue
Building 22, Room 4128
Silver Spring, MD 20993-0002
USA.
E-mail (GJ): gowra.jagadeesh@fda.hhs.gov
E-mail (KM-U): Khin.U@fda.hhs.gov
E-mail (PB): pbala2006@gmail.com

3
This article reflects the views of the authors and should not be construed to represent FDA’s
views or policies.

1
ABSTRACT

Noncommunicable diseases (NCDs) have become important causes of mortality on a

global scale. According to the report of World Health Organization (WHO), NCDs killed 38

million people (out of 56 million deaths that occurred worldwide) during 2012. Cardiovascular

diseases accounted for most NCD deaths (17.5 million NCD deaths), followed by cancers (8.2

million NCD deaths), respiratory diseases (4.0 million NCD deaths) and diabetes mellitus (1.5

million NCD deaths). Globally, the leading cause of death is cardiovascular diseases; their

prevalence is incessantly progressing in both developed and developing nations. Diabetic

patients with insulin resistance are even at a greater risk of cardiovascular disease. Obesity, high

cholesterol, hypertriglyceridemia and elevated blood pressure are mainly considered as major

risk factors for diabetic patients afflicted with cardiovascular disease. The present review sheds

light on the global incidence of cardiovascular disease and diabetes mellitus. Additionally,

measures to be taken to reduce the global encumbrance of cardiovascular disease and diabetes

mellitus are highlighted.

Keywords: Noncommunicable diseases; cardiovascular risk factors; cardiovascular disease

prevalence; diabetes mellitus; disease prevention

2
1. Introduction

According to the World Health Organization (WHO) report, noncommunicable disease

(NCD) deaths have been on the rise from 6.7 million in 2000 to 8.5 million in 2012 in the South-

East Asia area, and from 8.6 million to 10.9 million in the Western Pacific area [1]. Since 2000,

the number of deaths due to NCDs has augmented globally and in every region. While NCDs-

associated deaths are higher than all other causes combined, NCD deaths are projected to further

increase from 38 million in 2012 to 52 million by 2030 [1].

Cardiovascular diseases (CVDs) constitute the number one cause of mortality at the

global level; each year, more people die from CVDs than from any other cause [2]. According to

a WHO report, an estimated 17.3 million people died from CVDs in 2008, representing 30% of

all global deaths; it was projected that about 23.6 million people will die from CVDs, mainly

from heart disease and stroke by 2030 [2].

According to the WHO report, globally in 2012, of 56 million deceases, NCDs killed 38

million people. More than 70% (28 million) deaths happened in low- and middle-income

countries [3]. Of note, 16 million deaths due to NCDs occurred before the age of 70, with 82%

occurring in low- and middle-income countries [3].

The concept that CVD is a disease of affluence and only rampant in the western society is

no longer correct because, the prevalence of CVD is rising fast in the developing countries as

well. Among the NCDs, CVDs account for the highest number of NCD deaths (17.5 million

people annually); cancers are the second cause of NCD deaths (8.2 million), followed by

respiratory diseases (4 million), and diabetes mellitus (1.5 million). These 4 disease groups over

all account for 82% of all NCD deaths [3].

3
 In a recently published Medscape Medical News, heart disease (23.4% of all deaths),

cancer (22.5%), chronic lower respiratory disease (5.6%), accidents (unintentional injuries;

5.2%), cerebrovascular diseases (5.1%), Alzheimer's disease (3.6%), diabetes mellitus (2.9%),

influenza and pneumonia (2.1%), nephritis, nephrotic syndrome, and nephrosis (1.8%), and

intentional self-harm (1.6%) were the top 10 areas of death in 2014 in the United States. [57].

Together, these 10 causes of death accounted for 74% of all deaths in the United States [57].

In this article, we review various key cardiovascular risk issues, and the prevalence of

CVDs and diabetes mellitus. Additionally, we highlight potential ways to reduce the global

burden on CVDs and diabetes mellitus.

2. Cardiovascular risk factors

As per the World Heart Federation, cardiovascular risk factors are divided into 2 major

classes, viz. non-modifiable and modifiable risk factors [4].

2.1. Non-modifiable risk factors

The non-modifiable risk factors include age, gender and family history. Old people are

prone to have CVDs because of aging-associated structural and functional anomalies in heart and

vessels. Men are at higher risk for cardiac disease than pre-menopausal women, whereas post-

menopausal women may have a similar risk just like men [4]. Sudden cardiac death (SCD) often

occurs without previous cardiac symptoms. Of note, the high risk of premature death attributed

to SCD among men and women is almost 1 in 9 and 1 in 30, respectively. This should serve as a

motivator of public health efforts in preventing SCD [58]. Family history of incidence of stroke

or coronary heart disease (CHD) is also a vital non-modifiable risk factor for CVD incidence in

4
subsequent generation [4]. Regular check-up is highly recommended for people with non-

modifiable risk factors for CVDs.

2.1.1. CVD risk factors unique to the elderly population

The prevalence of CHD and morbidity from it increase with the age of population. When

evaluating the elderly population, age-specific CHD risk factors such as arterial stiffness, frailty,

lipid profiles and depressive symptoms should be considered [31]. As an individual is aging,

structural and functional changes in the vascular wall follow, including thickening of the arterial

wall and subsequent greater arterial stiffness. The arterial changes could lead to the development

of systolic hypertension, which increases left ventricular afterload causing left ventricular

hypertrophy [31]. Frailty, which is frequently seen in very old people, is also a risk factor for the

development of CHD. The lipid profiles levels affect the CVD risk of the elderly in a different

manner from that in a younger population. Neither high total serum cholesterol nor high LDL

levels predict cardiovascular mortality in very elderly population (>85 years); however, low

HDL level remains a risk factor for CHD death. Lastly, the elderly may suffer from depression

for various reasons, which might act as an independent risk factor for CHD in the elderly

population [31].

2.1.2. CVD risk factors unique to women

The prevalence of CHD in women is relatively less than men prior to the age of 50.

However, their prevalence of CHD rises significantly with age up to almost the prevalence rate

in men by the time they are in their seventh decade of life [31]. Almost 50% of women are

unaware that heart disease is the leading cause of death in women [31]. It is likely that for

women, the traditional methods to evaluate the risk of future coronary events may be inadequate.

5
While considering the cardiovascular risk for a woman, nontraditional factors that could increase

the CHD risk of a woman including cardiovascular conditions associated with pregnancy such as

preeclampsia, gestational hypertension, gestational diabetes mellitus, menopause-related

hormonal changes and autoimmune diseases that are common in women should also be

evaluated [31]. Apart from traditional risk factors for CVD (smoking, obesity and metabolic

syndrome, hypertension, physical inactivity, high lipids, and diabetes mellitus), the

aforementioned nontraditional risk factors for CVD are unique to women. At menopause, the

levels of endogenous estrogen fall to about one-tenth of the premenopausal levels, while

hormonal changes at menopause could independently produce a negative effect on HDL levels

and body fat distribution, and contribute to active progression of atherosclerotic lesions [31].

Women with hypertensive disorders of pregnancy are reported to have a statistically significant

augmented risk of cardiomyopathy [32].

2.2. Modifiable risk factors

Hypertension, use of tobacco, diabetes mellitus, physical inactivity, unhealthy diet,

cholesterol and lipids, and stress among others are collectively included under modifiable risk

factors [4]. Yusuf et al. [5] in the INTERHEART study from 52 countries reported potentially

modifiable risk factors associated with myocardial infarction that included smoking, raised

ApoB/ApoA1 proportion, history of hypertension, abdominal obesity, psychosocial aspects, and

regular alcohol ingestion among others. Risk factors are often observed in clusters so that even if

a person is detected with just one risk factor such as hypertension, a search for coexisting risk

factors such as smoking, central adiposity, hyperlipidemia and diabetes mellitus becomes

obligatory, because these risk factors occurring together can increase the risk of CVDs in a

multiplicative rather than in an additive manner [6].

6
2.2.1. Epidemiological data – hypertension

Among the risk factors that contribute to the development of CVDs, hypertension is the

most important, modifiable and independent risk factor.

Hypertension is a persistent elevation of systolic blood pressure of ≥140 mm Hg and a

diastolic blood pressure of ≥90 mm Hg. Hypertensive people are to develop diabetic

complications at a greater extent. Hypertension is the ‘silent killer’ as it occurs with no warning

signs or symptoms; it is regarded as one of the main causes of early death. It is therefore

imperative to have a regular blood pressure checkup. High blood pressure is one of the major

risk factors for death and for debility worldwide. Hypertension has a negative impact on the

function of heart and blood vessels. It is a risk factor for CHD and causes about 50% of ischemic

strokes and increases the risk of hemorrhagic stroke [7]. The factors contributing to hypertension

are given in BOX 1.

BOX 1: Behavioural factors contributing to hypertension [8]

1. Nearly half of hypertension may be attributable to consumption of unhealthy diet

(nearly 30% to high salt intake, and 20% to low dietary potassium through less
consumption of fruits and vegetables).

2. Physical inactivity is interrelated to nearly 20% of hypertension.

3. Obesity is correlated to nearly 30% of hypertension.

4. Excessive intake of alcohol is associated with hypertension. Additionally, quitting

tobacco use benefits hypertensive individuals.

7
 As per the WHO, in 2014, the global prevalence of elevated blood pressure in adults aged

18 years and above was about 22% [1]. Nearly one billion people have hypertension globally

from which two-thirds belong to developing countries [9]. About 330 million people in the

developed world and around 640 million in the developing world have hypertension. The

occurrence of high blood pressure in adults is estimated to reach 1.56 billion in 2025 [7]. About

60% of diabetic people have high blood pressure. Every year, hypertension kills nearly 8 million

people globally and nearly 1.5 million people in the South–East Asia section [10]. The

prevalence of hypertension in Indian adults has been estimated to be 30% (34% in urban areas

and 28% in rural areas) [11].

In the USA, Centers for Disease Control and Prevention (CDC) estimates that about 1 of

3 adults or about 70 million people have high blood pressure; however, only about half (52%) of

them maintain control of their high blood pressure [12]. A recent study suggests that

hypertension affects nearly 78 million U.S. adults and is an important modifiable risk factor

contributing to other CVDs and stroke [13]. In the data from the National Health and Nutrition

Evaluation Survey (NHANES) in 2007 to 2010, while 81.5% of individuals with hypertension

were aware of having high blood pressure, and 74.9% were treated, only 52.5% had their high

blood pressure under control [13]. Of note, about one fourth of adult population in the U.S have

hypertension while another quarter of the population have prehypertension, which is described as

systolic blood pressure of 120 to 139 mm Hg or a diastolic blood pressure of 80 to 89 mm Hg

[14].

A rising trend in the incidence of hypertension has been reported in a recent

epidemiological survey involving several countries and territories [59]. An increase in systolic

blood pressure (SBP) was found for both sexes in the regions of Oceania, East Africa, and South

8
and Southeast Asia, and for women in West Africa. SBP was found to be highest for women

(mean value of ≥135 mm Hg) in some East and West African countries, and for men (≥138

mm Hg) in Baltic and East and West African countries. In the Western Europe, both men and

women demonstrated highest SBP among the high income regions [59].

The key factors to slow the progression of the global prevalence of hypertension include

reducing salt intake, alcohol consumption and high dietary fat feasting. Additional factors

include eating adequate amount of fruits and vegetables, taking regular mild exercise, instituting

measures to reduce body weight in obese and overweight individuals, learning to relieve or cope

with stress, and initiating programs to improve socioeconomic status of communities.

2.2.2. Epidemiological data - tobacco use

According to the World Heart Federation, smoking is the second leading cause of CVD

after hypertension, and is estimated to cause nearly 10% of CVD [15]. The use of tobacco or

exposure to secondhand smoke kills nearly 6 million people globally every year. The tobacco-

related deaths have been projected to increase to more than 8 million deaths a year by 2030 [15].

Tobacco use damages blood vessels, temporarily raises blood pressure and lowers exercise

tolerance while it also decreases oxygen carrying capacity of blood and increases the clotting

tendency of blood, which could cause a range of CVD [15].

Smoking can raise blood triglycerides and decrease the HDL (the good cholesterol)

levels. Smoking can damage cells that line the blood vessels and increase the buildup of plaque

in blood vessels, causing thickening and narrowing of blood vessels. Breathing secondhand

smoke is known to cause stroke and coronary heart disease, including heart attack [16]. Even

briefly breathing secondhand smoke could cause damage in the blood vessel linings and cause

9
sticky blood, which could cause a deadly heart attack [16]. The adverse relationship between

tobacco use or secondhand smoke and CVD risk is shown in BOX 2.

BOX 2: Tobacco or secondhand smoke and CVD risk [15]

1. For every cigarette smoked, the risk of a non-fatal heart attack increases by 5.6%.

2. The risk of heart attack is likely to be more than double by chewing tobacco.

3. Breathing secondhand smoke increases in non-smokers the risk of developing a CVD by

25–30%.

4. Secondhand smoke contributes to 600,000 deaths annually, of which 28% are children.

5. The risk of a heart attack is almost doubled by frequent exposure to tobacco smoke at
workplace or home.

In the U.S, the tobacco use has declined markedly; yet, it occupies the place of second-

leading cause in total deaths and disability [17]. Nearly one third of CHD deaths are attributed to

smoking and secondhand smoke exposure [17].

Smoking is avoidable, and implementation of smoke free exercise and avoidance of

smoking habit could prevent associated CVDs.

2.2.3. Epidemiological data - physical inactivity

Physical activity is a crucial component of energy outflow, energy balance and weight

control. According to World Heart Federation, inadequate physical activity is the fourth leading

risk factor contributing to mortality. Insufficient physical activity may be defined as either less

10
than five times of 30 minutes moderate activity per week, or less than three times of 20 minutes

vigorous activity per week, or equivalent [18]. The benefits of exercise and physical activity

training include reduction in mortality from CVDs, increased exercise capacity and improved

quality of life. Undertaking more than 150 minutes of moderate physical activity a week or 60

minutes of vigorous physical activity a week can reduce the risk of CHD by about 30% [19].

Insufficient physical activity could increase the risk of all-cause mortality by 20% to 30% as

compared to individuals with at least 150 minutes of moderate intensity physical activity per

week, or equivalent [20].

In 2010, worldwide, 23% of adults aged 18+ years did not have sufficient physical

activity (men 20% and women 27%). According to the Global Health Observatory (GHO) data

of WHO, the highest prevalence of insufficient physical activity was observed in the Eastern

Mediterranean region (31%) and the region of the Americas (32%), whereas the lowest

prevalence was reported in the South-East Asia (15%) and African (21%) regions [20]. It should

be noted that women were less active than men across all regions. In addition, the popularity of

decreased physical activity varies with the size of income. In this context, 41% of men and 48%

of women from high income countries were inadequately physically active relative to 18% of

men and 21% of women from low income countries, according to the Global Health Observatory

(GHO) data of WHO [20]. Decreased physical activities have led to a higher incidence of

cardiovascular disease, diabetes mellitus, abnormal circulating lipids and obesity (BOX 3).

11
 BOX 3: Physical inactivity [21]

1. Decreased physical activity is one of the primary risk factors for CVDs and diabetes
mellitus. Inadequate physical activity is one of the ten leading risk factors for death on a
worldwide scale.

2. Globally, one in four adults is not sufficiently active.

3. Globally, over 80% of the adolescent population is inadequately physically active.

4. Children and adolescents of age 5 to 17 years need to do at least 60 min/day of moderate

to rigorous physical activity.

5. Adults aged 18–64 years need to do at least 150 min of moderate-intensity physical
activity throughout the week, or at least 75 min of vigorous-intensity physical activity
throughout the week.

6. If necessary, for added health benefits, adults could increase their moderate-intensity
physical activity to 300 min/week, or equivalent.

2.2.4. Epidemiological data - obesity

Obesity is a chronic disease affecting children, adolescents and adults alike. Excess body

weight is one of the leading causes of death and disability in the United States and globally; the

burden is expected to increase in coming years [17]. Obesity is associated with the chances of

developing hypertension, diabetes mellitus, CHD, stroke and osteoarthritis among others. The

levels of overweight and obesity are expressed in terms of the body mass index (BMI) of ≥25

kg/m2 and ≥30 kg/m2, respectively [1]. The global prevalence of obesity between 1980 and 2014

has nearly doubled. More than 1.9 billion adults of 18 years and above were overweight in 2014,

12
and of these, over 600 million were obese [22]. By gender, 11% men and 15% women aged 18

years and above were obese in 2014. In 2013, an estimated 42 million children under the age of 5

years were overweight [1]. The incidence of obesity is increasing in all countries. The prevalence

of overweight and obesity is highest in the regions of the Americas, i.e., 61% overweight or

obese in both sexes. On the other hand, it is lowest in the regions of South-East Asia, i.e., 22%

overweight in both sexes [1].

Of note, men are more likely to be less obese than women. In the regions of Americas,

Europe and Eastern Mediterranean, more than 50% of women are overweight, and about half of

these overweight women are obese (30% in the Americas, 25% in Europe, 24% in Eastern

Mediterranean countries) [1]. In the UK, the proportion of obese adults has markedly increased

from 13.2% in 1993 to 26.0% in 2013 for men and from 16.4% to 23.8% for women [23]. In the

United States, epidemic bursts of obesity declined among those from higher socioeconomic

status. On the other hand, it escalated among those from lower socioeconomic status. Moreover,

in the US youth especially among adolescent boys, the overall incidence of bursts of obesity

continued to increase [17].

Taken together, large intake of high-energy foods, such as refined and processed foods

can lead to obesity. An important public health message that must be emphasized to all is to

avoid highly processed foods prepared with refined white sugar, flour and saturated fat, and to

avoid high calorie foods.

2.2.5. Epidemiological data - unhealthy diet

Low consumption of fruits and vegetables and high consumption of saturated fats, trans-

fats and salt can increase cardiovascular risk and weight gain. Low fruits and vegetables intake is

13
believed to account for about 20% of CVD worldwide [24]. According to Global Health

Observatory (GHO) data of WHO, 1.7 million (2.8%) of global deaths may be the result of low

consumption of fruits and vegetables [25]. Conversely, adequate consumption of fruits and

vegetables could contribute to a reduction in the risk for CVDs, and colorectal and stomach

cancers [25]. In addition, WHO recommends less than 5 grams salt per day. Excess salt

consumption is an important determinant of high blood pressure and cardiovascular risk. It has

been suggested that reducing the level of dietary salt intake from 9 to 12 grams per day currently

consumed worldwide to the recommended level of 5 grams per day will contribute in a major

way to reduce the prevalence of high blood pressure and CVDs [25].

Likewise, consumption of large amounts of saturated fats and trans-fatty acids is

adversely associated with heart disease pathology and stroke. The safest strategy to prevent the

development of CVDs is through dietary intervention. The major categories of dietary fats

include saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated

fatty acids (PUFA). High consumption of SFA increases the risk of developing CVDs. On the

other hand, MUFA and PUFA are believed to be cardioprotective [26]. Human body synthesizes

SFA and MUFA; but, lacks the enzymes to synthesize PUFAs. Therefore, PUFAs are considered

essential fatty acids to be taken in the diet [26]. While many reports supporting the

cardioprotective effects of omega (n)-3 polyunsaturated fatty acids (PUFAs) exist, there are also

reports to the contrary.

According to epidemiologic and interventional studies, substituting MUFA-rich foods for

SFA-rich foods in the diet might reduce total plasma cholesterol concentrations, but do not

lessen the extent of coronary artery atherosclerosis [27]. To precisely understand the claims of

14
cardioprotective effect, if any, of MUFA and n-3 PUFA, more studies are to be conducted at the

clinical and epidemiological levels.

2.2.6. Epidemiological data - hyperlipidemia

Globally, about one third of ischemic heart disease is attributed to elevated cholesterol

[28]. The risk of heart disease could be decreased by lowering the raised blood cholesterol.

Globally, the socioeconomic status of a country influences the prevalence of elevated total

cholesterol. In 2011, about 25% of adults from low-income countries and more than 50% of

adults from high-income countries experienced elevated total cholesterol [29].

One of the major risk factors for CVD and stroke is high cholesterol. According to the

American Heart Association, one of the seven components of ideal cardiovascular health is that

the untreated total cholesterol of <170 mg/dL for children and of <200 mg/dL for adults [30].

Dyslipidemia and disturbances in the homeostatic regulation of lipid and lipoprotein

metabolism play a prime role in development of CVD. A reduction in the low-density lipoprotein

(LDL)-cholesterol continues to be the primary goal to lessen the progression of CVDs. However,

despite maintaining optimal levels of LDL-cholesterol, cardiovascular disease still remain

prevalent, suggesting that other lipids and risk factors need to be modulated as well. Current

therapies emphasize lowering blood triacylglycerol levels and augmenting high-density

lipoprotein (HDL)-cholesterol levels. In addition to these therapeutic approach, lifestyle

modifications, especially maintaining a low intake of fats in the diet, will play an important role

to prevent CVD.

15
2.2.7. Depression as a CVD risk factor

Depression appears to be an independent risk factor contributing to the onset of a wide

range of CVDs [33]. Proposed biologic mechanisms include altered sympathetic stimulation and

changes in lipid metabolism found in association with depression. Other associated behaviors of

depression contributing to the development of CVD may be stress, physical inactivity and

medication non-adherence.

An estimated 15.4 million US adults with CHD have depression and elevated depressive

symptoms. About 20% of patients admitted to a hospital for an acute coronary syndrome such as

myocardial infarction or unstable angina were suggested to meet the American Psychiatric

Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for major

depression; and even a higher number showed subclinical levels of depressive symptoms [34].

Diabetic patients are suggested to be approximately three times likely to have depression than

their nondiabetic counterparts, while diabetic patients are already predisposed to a greater risk

for poor cardiovascular health. A recent study suggested that those who were depressed have had

higher HbA1c levels and BMIs than those who were not depressed, indicating that depressed

diabetic patients are at higher risk of having meager control of cardiovascular risk factors [35]. In

addition, a recent study suggested that an association exists between anxiety and increased risk

of hypertension [36].

3. Global/regional prevalence of various types of cardiovascular disease

Cardiovascular disease refers to diseases of the circulatory system affecting the anatomy

and physiology of the heart and blood vessels. The most common types of CVD include

hypertension (prevalence information provided in previous sections), ischemic heart disease,

16
cerebrovascular disease (stroke), peripheral vascular disease, heart failure, rheumatic heart

disease, valvular heart disease and congenital heart disease.

3.1. Ischemic heart disease

Ischemic heart disease (or coronary artery disease) is associated with reduced blood

supply to the heart. Ischemic heart disease could develop with high cholesterol, hypertension,

chronic diabetes mellitus, abdominal obesity, lack of exercise, not having sufficient fruits and

vegetables, large ingestion of alcohol, smoking and stress. According to the WHO, in 2012,

ischemic heart disease (7.4 million deaths) has been the leading cause of death in the world,

followed by stroke (6.7 million deaths), chronic obstructive pulmonary disease (3.1 million

deaths), and lower respiratory infections (3.1 million deaths), among others [37]. Among the 10

leading causes of death by country income group (2012) listed by WHO, ischemic heart disease

remains at the top only in lower-middle income countries and in high-income countries [38]. On

the other hand, in low-income countries and upper middle-income countries, ischemic heart

disease is placed at the 5th and 2nd positions, respectively, among the top 10 causes of death in

2012 [38].

According to the data from the National Health and Nutrition Examination Survey

(NHANES) 2009 to 2012, an estimated 15.5 million Americans of age ≥20 years have had CHD,

while the prevalence of CHD was 7.6% and 5.0% for men and women, respectively [30].

17
3.2. Cerebrovascular disease-Stroke

The second leading cause of disability after dementia is stroke. Stroke results from

blockade by a clot or from rupture of blood vessel carrying oxygen and nutrients to the brain.

Ischemic stroke results from a clot obstructing the blood flow to the brain. A hemorrhagic stroke

is the result of a blood vessel rupturing and preventing blood flow to the brain. A transient

ischemic attack results from a temporary clot.

When looking into the worldwide burden of stroke, the World Heart Federation found

that every year 15 million people suffer from a stroke. Nearly six million people die and another

five million are left permanently disabled [39]. Disability might include loss of vision and or

speech, paralysis and confusion. On a global scale, stroke is the second leading cause of death in

people aged >60 years, and the fifth leading cause of death in people aged 15 to 59 years [39].

The incidence of stroke is declining in many developed countries although the actual number of

strokes is increasing as a result of the ageing population. It is predicted that stroke mortality in

Latin America, Middle East and sub-Saharan Africa might triple in the next 20 years [39].

According to the NHANES 2009-2012 data in the USA, an estimated 6.6 million people

of age ≥20 years had a stroke. During this period, the overall stroke prevalence is an estimated

2.6% (NHANES, National Heart, Lung, and Blood Institute-NHLBI). The 2013 data from the

Behavioral Risk Factor Surveillance System-Centers for Disease Control and Prevention

(BRFSS- CDC) showed that 2.7% of men and 2.7% of women of age ≥18 years have had a

history of stroke [30]. On average someone in the US has a stroke every 40 seconds [30]. In

2013, someone died of a stroke on average every 4 minutes. This disease accounted for nearly 1

of every 20 deaths in the US [30].

18
 Recently, Feigin et al [40] systematically analyzed data from the Global Burden of

Disease Study 2013 to estimate the population-attributable fraction (PAF) of stroke-related

disability-adjusted life-years (DALYs) connected with adjustable environmental, occupational,

behavioural, physiological, and metabolic risk factors in different age and sex groups globally

and in high-, middle-, and low-income countries during 1990 and 2013. The researchers

estimated the disease burden of stroke linked with 17 risk factors in 188 countries. The

researchers reported that globally, 90·5% of stroke burden, as measured in DALYs, was

attributable to modifiable risk factors with 74·2% due to behavioural factors including smoking,

low quality diet, and less physical activity, and suggesting that 90% of stroke burden might

theoretically be avoided by controlling these risk factors. Clusters of metabolic factors (elevated

SBP, high BMI, high fasting plasma glucose, high total cholesterol, and low glomerular filtration

rate; 72·4%) and environmental factors (air pollution and lead exposure; 33·4%) were the second

and third largest contributors to DALYs. The percentage contribution of individual risk factors

adds up to over 100% because they all interact with each other, and one risk factor is often

regulated through other risk factors. It is inferred from the study that greater than 90% of the

stroke problem is attributable to modifiable risk factors, while attaining control of behavioural

and metabolic risk factors could prevent above three-quarters of the worldwide stroke burden

[40].

3.3. Peripheral arterial disease

Peripheral arterial disease is common in the legs or lower extremities where narrowing or

blockage of the vessels occur mainly because of the buildup of fatty plaque in the arteries

(atherosclerosis). While peripheral arterial disease could occur in any blood vessel, it is more

common in legs than in arms. Its classic symptom is pain in legs upon exertion which is relieved

19
by resting. Risk factors for peripheral arterial disease mainly include smoking, high blood

pressure, atherosclerosis, diabetes mellitus and high cholesterol [41]. The risk factors for

peripheral arterial disease are related, but not identical to those for CHD. Cigarette smoking and

diabetes mellitus are considered stronger risk factors for peripheral arterial disease than for CHD

[30].

In the 21st century, peripheral artery disease has become a worldwide problem. Following

coronary artery disease and stroke, lower extremity peripheral artery disease has been the third

leading cause of atherosclerotic cardiovascular morbidity [42]. In 2010, there were 202 million

individuals afflicted with peripheral artery disease living worldwide, while 69·7% of them were

living in low-income or middle-income countries, including 54·8 million from Southeast Asia

and 45·9 million from the Western Pacific countries [42].

Peripheral artery disease is associated with high morbidity and mortality affecting about

8.5 million Americans aged ≥40 years [30]. The maximum occurrence of this disease has been

observed among aged people. In general, only about 10% of people afflicted with peripheral

artery disease have had the classic symptoms of intermittent claudication while around 40% of

people did not complain of leg pain [30]. On the other hand, the remaining 50% have had a

variety of leg symptoms different from that of classic claudication [30].

3.4. Heart failure

Heart failure is a condition in which the heart is unable to pump enough quantity of blood

to meet demands of the body. Either the heart cannot fill with enough amount of blood or it

cannot pump blood with enough force to supply adequate blood to the circulation. Right-side

heart failure occurs when the heart is unable to pump sufficient amount of blood to the lungs for

20
oxygenation/purification, while left-side heart failure occurs when the heart is unable to pump

appropriate amount of oxygenated blood to the rest of the body.

Globally, heart failure is a major public health problem. Its global prevalence is more

than 23 million [43]. Heart failure has been associated with significant mortality, morbidity and

healthcare expenditures mainly in people aged ≥65 years [43]. Heart failure is common

throughout the sub-Saharan Africa and it strikes individuals in the sub-Saharan Africa at a much

younger age than in the United States and Europe [30]. In fact, heart failure has been an

imperative contributor to CVD burden in the sub-Saharan Africa for many decades [44].

According to the NHANES 2009 to 2012 data, an estimated 5.7 million Americans aged

≥20 years have had heart failure [30]. It is projected that from 2012 to 2030, the heart failure

prevalence will increase 46% resulting in >8 million people aged ≥18 years with heart failure

[30]. Furthermore, nearly 50% of people diagnosed with heart failure have been suggested to die

within 5 years [30].

3.5. Rheumatic heart disease

In the 21st century, rheumatic fever and rheumatic heart disease have remained relatively

unheeded diseases in indigent communities. Acute rheumatic fever and subsequent rheumatic

heart diseases have been almost eradicated in areas with economic growth and prosperity.

However, migration of individuals from low-income countries to high-income regions could

contribute to a new wave of an unanticipated prevalence of rheumatic heart disease in high-

income countries. World-wide, rheumatic heart disease remains the most prevalent CVD among

young people aged <25 years [45].

21
 Rheumatic heart disease affects over 32 million people worldwide and claims 275,000

lives annually [48]. The most severely affected regions include the sub-Saharan Africa, south-

central Asia, the Pacific and indigenous populations of Australia and New Zealand [46].

Importantly, signs of rheumatic heart disease are found in about 1% of all schoolchildren in Asia,

Africa, the Eastern Mediterranean region, and Latin America [46]. In American Samoa,

rheumatic heart disease is approximately 10 times more common than in the continental United

States and a high prevalence of lifelong morbidity from rheumatic heart disease is projected [47].

In the United States, the annual incidence of acute rheumatic fever declined in the late 20th

century to around 0.04–0.06 cases per 1,000 children; rheumatic fever is no longer a notifiable

disease in the United States [47].

Recurrent or severe acute rheumatic fever could result in permanent damage to the

cardiac valves and rheumatic heart disease [47]. Antibiotics, if administered no more than 9 days

after the onset of symptom, can prevent acute rheumatic fever [47]. Long-term benzathine

penicillin G injection is effective in averting recurrent acute rheumatic fever attacks and the CDC

(Centers for Disease Control and Prevention) recommends it to be given every 3-4 weeks for 10

years or until the age of 21 years to children diagnosed with acute rheumatic fever [47].

3.6. Valvular heart disease

Valvular heart disease (VHD) is a structural or functional abnormality of cardiac valves.

The main causes of VHD are calcific aortic stenosis in the elderly, floppy mitral valve/mitral

valve prolapse associated with mitral regurgitation, bicuspid aortic valve, VHD associated with

cardiomyopathy, post-interventional therapy (iatrogenic) and infective endocarditis among others

[60]. The incidences of VHD increase over the past few decades probably due to aging

22
population, increased survival in patients afflicted with conditions like ischemic heart disease

and inflammatory disease states, and earlier diagnoses due to advanced technologies [61]. The

prevalence of VHD is estimated at 2.5% in industrialized countries [62]. A recent trend observed

has been a marked increase in the prevalence of valvular disease after the age of 65 years,

particularly with regard to aortic stenosis and mitral regurgitation [62]. Rheumatic heart disease

represents 22% of VHD in Europe [62]. While Rheumatic heart disease remains an important

factor for development of VHD globally, degenerative valve diseases are likely the most

common causes of VHD in developed countries [61].

3.7. Congenital heart disease

Congenital heart disease is linked with defectiveness in the structure of heart existing at

birth. Congenital heart faults could change the normal flow of blood through the heart.

Congenital heart disease accounts for about one-third of all major congenital anomalies [49]. The

worldwide prevalence of congenital heart disease birth varies and is not available accurately.

Asia reported the highest incidence of congenital heart disease birth with 9.3 per 1,000 live births

[49]. The total congenital heart disease birth incidence reported in Europe was markedly higher

than in North America (8.2 per 1,000 live births vs. 6.9 per 1,000 live births) as per the report of

a systematic review and meta-analysis published in 2011 [49]. Major advances in medical and

surgical therapies of congenital heart disease over the past 4 decades have enabled many infants

born with congenital heart disease to survive to adult and older ages [50], with >85% of children

with congenital heart disease surviving to adulthood [51].

The congenital heart disease incidence at birth in any population depends on how a

population is studied because before imaging techniques such as echocardiography became

23
available, the incidence has ranged from five to eight cases of congenital heart disease diagnosed

per 1000 live births [52]. Following the development of advanced diagnostic procedures in

recent years, many milder forms of congenital heart disease were able to be identified; thus, the

estimates have ranged from eight to 12 per 1000 live births [52].

The incidence of congenital heart defects in the US is generally reported between 4 and

10 per 1000, clustering around 8 per 1000 live births [30]. Incidence rates over the time might

increase because of superior detection during infancy by fetal cardiac ultrasound, screening pulse

oximetry and echocardiography [30].

Recent medical advances resulting in improved survival from congenital heart diseases

have created a shift in their demographics. From 2000 to 2010, the prevalence of congenital heart

disease had increased by 11% only in children but a staggering 57% in adults [63]. In a similar

manner, the prevalence in the severe congenital heart disease subgroup had increased by just

19% in children but a large proportion (55%) in adults [63]. Adults have now become a

significant patient population constituting a majority of congenital heart disease patients. There

is an urgent and growing need to train more physicians who are knowledgeable on adult

congenital heart disease and who can assess and manage these patients with complex heart

defects.

4. Global/regional prevalence of diabetes mellitus

Diabetes mellitus is a chronic disease that happens when the pancreatic beta cells of islets

of Langerhans are unable to produce sufficient insulin (type 1 diabetes mellitus, insulin-

dependent, juvenile or childhood-onset diabetes) or when the body ineffectively uses the insulin

(type 2 diabetes mellitus, non-insulin-dependent or adult-onset diabetes). Type 2 diabetes

24
mellitus is the most common form of diabetes characterized by elevated blood sugar, insulin

resistance and relative lack of insulin. The hormone insulin regulates blood sugar, and thus

deficient insulin secretion or its ineffective body’s use could result in hyperglycemia.

The precise cause of type 1 diabetes mellitus is not known; its primary symptoms include

frequent urination, high level of thirst, weight loss, and fatigue, and, over time, changes in vision,

kidney function and sensory/motor nerve function in extremities. The symptoms of type 2

diabetes mellitus might be similar to those of type 1 diabetes mellitus, but are often less marked,

and therefore, the presence of type 2 diabetes mellitus may be undiagnosed for many years until

complications such as peripheral neuropathy, peripheral vascular disease or kidney disease

manifest with symptoms [53]. Chronic and uncontrolled diabetes mellitus is linked to several

complications, including retinopathy, neuropathy and nephropathy, among others [54].

Suboptimal control of diabetes mellitus could have damaging effects on multiple systems in the

body and could result in life-threatening difficulties [55]. The risk factors for type 2 diabetes

mellitus are listed in BOX 4.

Globally, the number of adults afflicted with diabetes mellitus has increased from 108

million in 1980 to 422 million in 2014 [53]. The global prevalence of diabetes mellitus in adult

population has increased from 4.7% in 1980 to 8.5% in 2014. This indicates that the global

prevalence (age-standardized) of diabetes mellitus has nearly doubled since 1980 until 2014 [53].

For the past 10 years, the occurrence of diabetes mellitus has increased in countries with low-

and middle-income than in countries with high-income [53].

25
 BOX 4: Risk Factors for Type 2 Diabetes Mellitus [56].

The following features are likely to be observed in individuals who develop type 2 diabetes
mellitus:

1. Age ≥45.

2. Overweight or obese.

3. Sedentary lifestyle.

4. Family history with diabetes mellitus.

5. History of delivering a baby weighing >9 pounds.

6. Polycystic ovary syndrome; and history of diabetes mellitus during pregnancy.

7. Elevated blood pressure (≥140/90 mmHg) or being treated for hypertension.

8. Levels of major lipids: High-density lipoprotein below 35 mg/dL, or triglycerides above 250
mg/dL.

9. Prediabetes—HbA1C level of 5.7 to 6.4 percent; an elevated fasting plasma glucose test
result of 100–125 mg/dL; or a two-hour oral glucose tolerance test result of 140–199
mg/dL.

10. Acanthosis nigricans presenting with a dark, velvety rash around the neck or armpits.

11. Current or prior history of CVDs.

In 2012, the total burden of deaths from high blood glucose was 3.7 million. Diabetes

mellitus directly caused 1.5 million deaths, while increased risks of cardiovascular and other

diseases resulting from higher-than-optimal blood glucose contributed to an additional 2.2

million deaths [53]. Forty three percent of these 3.7 million deaths occurred prior to the age of 70

26
years. The death percentage attributed to either elevated blood glucose or diabetes mellitus that

have occurred before the age of 70 years was higher in countries with low- and middle-income

than in countries with high-income [53].

In the USA, diabetes mellitus affects 1 in 10 adults with 90% to 95% being type 2

diabetes mellitus [17]. Although type 2 diabetes mellitus has been historically diagnosed mainly

in adults of age 40 years and more, it is progressively common in children and youths. In

children/youths, its prevalence has been shown to be increased by 30.5% between 2001 and

2009, and it now constitutes nearly 50% of all childhood diabetes mellitus [17]. Diabetes

mellitus is generally characterized with shortened life expectancy; men and women afflicted with

diabetes mellitus live an average of 7.5 and 8.2 years less, respectively, than those who are

devoid of diabetes mellitus [17]. Rampant bursts of childhood and youth obesity through more

sedentary lifestyles (such as increased television and computer usage and decreased physical

activity) and modifications to nutrition (increasing calorie intake) have led to a higher prevalence

of type 2 diabetes mellitus in younger generation. Postponing the early onset of type 2 diabetes

mellitus in youngsters will be a major influence on the future burden of the diabetes mellitus,

because onset of diabetes at a very young age presages many years of disease and a buildup of

the full range of both micro- and macrovascular complications.

27
 Reduction in the risk of type 2 diabetes mellitus and improvement of insulin sensitivity

and glucose uptake could effectively be achieved by engaging in regular physical activity and

having healthy diets, including consumption of dietary fiber foods and substitution of saturated

fatty acids with polyunsaturated fatty acids [53]. The WHO and the Food and Agriculture

Organization (FAO) recommend limiting the intake of saturated fatty acids to less than 10% of

total energy intake, while this intake should be less than 7% for high risk individuals to prevent

type 2 diabetes mellitus [53]. It is imperative to achieve adequate intakes of dietary fiber,

specifically a minimum daily intake of 20 gram, by regular consumption of wholegrain cereals,

legumes, fruits and vegetables [53]. WHO also advises to reduce the ingestion of free sugars to

less than 10% of total energy intake and that reduction to 5% could provide additional health

benefits [53].

5. Steps ahead to reduce the global burden of mortality and morbidity

from high prevalence of cardiovascular disease and diabetes mellitus

Efforts to reduce the global burden of mortality and morbidity from high prevalence of

cardiovascular disease and diabetes mellitus can be focused at the level of the individual or the

population. At the individual level, actions needed to prevent and treat CVD appear

straightforward: eat a healthy, low-salt, low-fat diet, remain physically active throughout life,

preserve normal body weight, do not use tobacco, and seek health care regularly. In reality,

however, the actions are much more complex. Behavioral change is difficult, individual choices

are influenced and often constrained by broader social and environmental factors, and many

people do not have the resources or access to seek appropriate healthcare, education and

community-based programs at schools or workplaces.

28
 At the level of health management organizations such as the ministries of health or the

World Health Organization, awareness and actions in the following areas of providing health

care at country and community levels are recommended [64]:

(i) Addressing the magnitude of the problem of CVD and diabetes mellitus: The health

management organizations need to fully understand the determinants of the growing problems of

CVD and diabetes mellitus in the country/community, the proximate risk factors (genomic,

biological [hypertension, dyslipidemia] and behavioral [diet, salt intake, physical activity,

tobacco]) and the upstream factors such as demographic change, economic development, social

variation, education, cultural norms, urbanization trends and globalization [65].

(ii) Active collaboration of health organization in their efforts to improve diets in minimizing the

incidence of CVD and diabetes mellitus: The WHO and the World Heart Federation along with

governments from developing and developed nations might need to coordinate for cultivating

highly effective strategies to improve the regular diet through reduction of dietary intake of salt,

sugar and saturated fats [66].

(iii) Accelerating the rates of determination of the burden of CVD and diabetes mellitus in

different localities in low- and middle-income countries (LMIC), taking into consideration the

change in demographics (population growth and aging) and the prevalence of risk factors (high

blood pressure, diabetes mellitus, smoking, obesity, lack of exercise, unhealthy diet and alcohol)

is an important measure to reduce the prevalence of CVD and diabetes mellitus [65].

(iv) Availability of essential medicines for CVD and diabetes mellitus: Improve selection of

essential medicines and create incentives in public and private sectors to make low-price, quality

assured medicines availability. A meta-analysis of surveys from 36 countries for access to 5

29
drugs used to treat CVD (atenolol, captopril, losartan, nifedipine and hydrochlorothiazide) found

that these medicines were available in only around 26% of public health facilities and around

57% of private health care facilities [67].

(v) Affordability of essential medicines for CVD and diabetes mellitus: Reduce or abolish taxes

on essential medicines, control markups, improve insurance programs to include a basic package

of affordable medicines, provide incentives to manufacture quality generic formulations of

essential medicines.

(vi) Accessibility to essential medicines for CVD and diabetes mellitus: Improve the accessibility

by increasing operational hours of clinics, providing free or subsidized clinics, and streamlining

clinic procedures to reduce waiting times and improve patient satisfaction. In some countries,

long travel times may be required for patients to reach a health facility.

(vii) Acceptability of essential medicines for CVD and diabetes mellitus: Improve the

acceptability possibly by making available fixed-dose combinations (FDCs, e.g., Polypill), and

reporting outcomes of large population-based outcome studies to demonstrate efficacy, safety

and acceptability of the FDCs. Inadequate prescription and poor adherence to medication have a

marked impact on CVD globally.

(viii) Allocation of resources: Governments in LMIC, local communities and NGO donors need

to balance many competing priorities when allocating resources. These countries have to

recognize and respect the realities of multiple competing priorities in their allocation of resources

so that other health priorities (such as AIDS, malaria, tuberculosis) would not be adversely

affected as a result of greater attention to CVD.

30
(ix) Advocacy, advertising and education efforts: International advocacy efforts to raise

awareness of the growing epidemic of CVD and diabetes mellitus in LMIC have increased in

intensity over the past decades. However, these efforts have not yet resulted in established and

successful programs to reduce the prevalence of these diseases. There need to be more effective

communication of the steps that should be taken for the long term. Strategies using mass media,

media advocacy, social marketing, and social mobilization can serve to mobilize support among

various other stakeholders in the global health arena.

(x) Approach to shared-risk-factor reduction, health promotion, quality health care, and health

systems strengthening in an integrated manner is critical. Within this approach there is a need for

disease-specific approaches in some areas (such as training the health workforce to effectively

implement secondary prevention and treatment), and for investment in scalable CVD-specific

diagnostic tools and interventions such as medications for hypertension or dyslipidemia.

(xi) Adopting and maintaining suitable environment that leads to lifelong heart-healthy lifestyles,

from childhood to adult and old age.

6. Concluding remarks

CVDs and diabetes mellitus are the two leading NCDs. They account for most NCD

deaths worldwide. The most common types of CVDs are hypertension, CHD, peripheral artery

disease, stroke, heart failure, rheumatic heart disease, VHD and congenital heart disease. The

development and prevalence of CVDs and their clinical impact and attributable risk are strongly

influenced by modifiable and non-modifiable risk factors. Unhealthy diet and insufficient

physical activity, the two major current changes in the behavioral pattern of societies worldwide,

are common risk factors for both CVDs and diabetes mellitus. Individuals with diabetes mellitus

31
are at increased risk of CVDs; these individuals often have comorbid factors like hyperlipidemia,

atherosclerosis, obesity and sedentary life style, which could further contribute to their risk for

developing CVDs. There is a need for a detailed, up-to-date understanding of progress of these

diseases, reporting programs and control strategies to be available at all levels: global, national

and local. Awareness of the prevalence of CVDs and diabetes mellitus among countries and

donor organizations worldwide strengthens their efforts in identifying gaps in admittance to

appropriate health care and health education, and implementing adequate measures to lessen the

burden of CVDs and diabetes mellitus. Furthermore, a global partnership of nationwide public

health campaigns should be organized to create awareness among the public with information

pertaining to the primary prevention and management of CVDs and diabetes mellitus.

32
Conflict of Interest

No conflict of interest exists.

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