Elevated blood pressure (BP) is a growing health problem in South Asia, where it is the second largest risk factor for disability-adjusted life years lost, predominantly because of its strong relationship with cardiovascular disease (CVD) development. Within India, it has been estimated that hypertension accounts for 57% of all stroke related deaths and 24% of coronary artery disease related deaths. Thus, a significant proportion of death and disability in the region can be reduced by improving BP control.
In South Asia, there has been a steady rise in both the age- and sex-adjusted mean population BP, and the prevalence of hypertension, over the past two decades. Significant gaps in hypertension management are also present across South Asia, with less than half of individuals with high BP aware of it, and poor control in more than 80% with high BP. If left unaddressed, these trends will substantially increase CVD morbidity and mortality related to elevated BP. This chapter will focus on the epidemiology of hypertension and its management in South Asian populations. First we will examine the prevalence of hypertension, and its variation across South Asia. Next, we will examine the major modifiable and genetic risk factors associated with hypertension incidence in South Asians, and finally, we will summarize current gaps in hypertension management that need to be addressed in the region.
Prevalence of Hypertension in South Asian Populations
Definition of Hypertension in the South Asian Population
It has been recommended that some CVD risk factors in South Asians (e.g., obesity) warrant lower thresholds to define risk when compared with other ethnic groups. This is because of evidence that CVD in South Asians occurs at lower age and risk factor thresholds. Studies also suggest that certain physiologic BP parameters (e.g., pulse pressure, postexercise BP) differ, and that BP may have a stronger association with stroke risk in South Asians compared with white Europeans. However, there is no definitive evidence that, for a given BP, South Asian populations are at a higher CVD risk, and a systolic blood pressure (SBP) greater than 140 mm Hg and/or diastolic blood pressure (DBP) greater than 90 mm Hg remains the currently accepted threshold to diagnose hypertension in South Asian populations.
Prevalence of Hypertension in South Asia
Estimates of hypertension vary substantially across countries in South Asia, which is partly due to demographic differences between the populations studied. For example, in a systematic review of 33 observational studies (of 220,539 participants, with a mean age of 43.7 years) from seven countries in South Asia, the prevalence of hypertension was approximately 27%, ranging from 17.9% in Bangladesh to 33.8% in Nepal. By contrast, in the Prospective Urban Rural Epidemiology (PURE) study, which studied a slightly older population cohort of 33,000 participants (mean age 48.5 years, age range 35 to 70 years) from India, Pakistan, and Bangladesh, hypertension was diagnosed in one-third of individuals, with the highest prevalence in Bangladesh (39.3%), followed by Pakistan (33.3%), and lowest in India (30.7%). Despite these observed differences between studies, the prevalence of hypertension has been consistently shown to be higher in men compared with women, and in urban compared with rural areas.
In fact, transition from the rural to urban environment is a key societal factor driving the increasing prevalence of hypertension. In India, the prevalence of hypertension has increased dramatically over the past several decades with a higher burden reported in urban areas. In a systematic review of 142 studies conducted in India, it was estimated that 29.8% of adults had hypertension; and in urban areas, where extensive changes in health-related behaviors have already occurred, the prevalence of hypertension was higher (33.8%) compared with rural areas (27.6%) ( Fig. 4.1 ). Furthermore, the prevalence of hypertension varied substantially in rural areas (which was not observed in urban areas) likely reflecting the different stages of economic development, urbanization and transitions in health-related behaviors occurring across rural environments in India.
Prevalence of Hypertension in South Asians Who Have Migrated to North America or Europe
Compared with other ethnic groups living in the same macroenvironment, South Asians have a unique cardiovascular risk profile, characterized by a higher risk of diabetes, higher percent body fat, and lower high density lipoprotein concentration compared with other ethnic groups. Some studies suggest that the risk of hypertension is also modestly increased in South Asians compared with Caucasians living in the same country. In a systematic review of 13 hypertension prevalence studies (n ≈ 650,000 individuals) in Canada, the risk of hypertension was slightly higher in South Asians compared with Caucasians (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.02 to 1.22, p = 0.02). However, this association has not been consistently observed among South Asian populations residing in Europe. Also, while the prevalence of some cardiovascular risk factors (e.g., obesity) appear to be steadily increasing in these South Asian populations over time, whether such a trend is also occurring with the prevalence of hypertension is not clearly established.
Risk Factors for Hypertension in South Asian Populations
Genetic Factors
Although it is estimated that 30% to 70% of the phenotypic variance of BP is heritable, at the population level, only a small fraction of this variance has been explained by common genetic polymorphisms through genome wide association studies (GWAS).
GWAS have identified approximately 70 single nucleotide polymorphisms (SNPs) associated with BP. Although most of these were identified in white European populations, approximately one-fifth appear to be shared in South Asians. Metaanalysis of 28 GWAS studies in 69,395 participants of European ancestry identified 28 independent loci significantly associated with either SBP or DBP of which six were also significantly associated with BP in 23,977 participants of South Asian ancestry. Also, a recent transethnic metaanalysis of 320,251 participants of European, South Asian, and East Asian origins identified polymorphisms from 12 independent loci associated with BP traits, with consistent effects across all three ethnic groups. These studies suggest that South Asians share a similar genetic predisposition to hypertension compared with other ethnic groups. However, GWAS have thus far failed to identify polymorphisms unique to South Asians that impact BP; although this may be because of methodologic factors, such as the relatively small sample sizes (and limited power) of current GWAS performed in South Asians, the limited power of GWAS to identify significant effects associated with rare polymorphisms, and differences in linkage disequilibrium between ethnic groups. Some genetic associations may be further impacted by gene-environment interactions, which could result in different genetic effects between ethnic groups when patterns of health-related behaviors also differ.
Modifiable Risk Factors for Hypertension
Risk factors for hypertension development are examined in detail in Section III of this book. Of these, several are of particular importance in South Asian populations because of their high prevalence or increasing burden within the region.
Overweight and obese: It is estimated that the risk of hypertension increases by 20% for each 5% gain in weight, and in South Asian populations obesity (commonly defined as body mass index ≥25 kg/m 2 for this group) is a common risk factor for both hypertension development, and poor hypertension control. In the past two decades, the prevalence of obesity has increased across the region; and in India, approximately 9% of men and 13% of women now meet clinical criteria for obesity, with a higher prevalence in South India, in urban areas and among women.
Diabetes is associated with a three-fold to four-fold increase in the risk of hypertension in South Asian populations; and its prevalence in South Asia is now among the highest in the world. In India, between 5% and 15% of individuals have diabetes depending on geographic location, with a similar prevalence reported among men and women, and a higher prevalence in urban areas.
Smoking and alcohol consumption are each associated with a 1.5-fold to two-fold increase in hypertension risk in South Asian populations. Both are substantially more common in men compared with women. National survey data from India report that 29% of men currently smoke, as compared with only 2% of women. Similarly, regular alcohol use has been reported in 8% of males compared with only 1% of females.
The nutrition transition in India as a consequence of urbanization and economic development has resulted in lower consumption of fruits, vegetables and fiber; higher consumption of saturated fats/meat products; and higher sodium consumption. Although there is limited evidence examining how diet impacts BP in South Asians, available data in this population suggest that low fruit and vegetable consumption, higher fat consumption, and higher discretionary sodium consumption are associated with hypertension. Mean sodium consumption in the South Asian population is currently estimated between 3.5 and 4 g/day, a range where there is no clear impact on CVD risk. However, in individuals who consume higher amounts of sodium (e.g., >5 g/day), counselling on dietary sodium reduction should occur.
In individuals without hypertension, regular physical activity modestly reduces BP. However, epidemiologic data suggest that 54% of adults in India are physically inactive, with lower levels of physical activity occurring in urban areas, and among men. Furthermore, 85% of individuals do not engage in any recreational physical activities. Although this may be partly counterbalanced by obligatory physical activity (e.g., occupational activities), a greater public health emphasis on policies that promote physical activity is still needed.
Management of Hypertension in South Asians
Lifestyle and Behavioral Modification
Adopting healthy behaviors is an important component for both preventing hypertension and reducing BP in patients with established hypertension. Particular emphasis should be placed on weight loss in overweight or obese individuals, reducing sodium consumption in those with high sodium intake (e.g., >5 g/day), increasing fruit and vegetable intake, and reducing saturated fat intake. Smoking avoidance or cessation, and limiting alcohol consumption should be promoted in all individuals, with a particular focus on men, where the prevalence of both is substantially higher compared with women. Increasing physical activity can reduce BP both directly and indirectly through weight loss. In patients with hypertension, these lifestyle changes have each been shown to have small to moderate effects on BP reduction (ranging between 2 and 3 mm Hg for SBP), but the promotion of a healthy lifestyle also reduces CVD risk independent of BP lowering, and should be encouraged in all individuals with and without hypertension.
Initiation of Antihypertensive Therapy and Treatment Targets
Most patients with hypertension will require both lifestyle modification and pharmacologic therapy to control BP. There is no consistent evidence to suggest that BP targets should differ in South Asian populations compared with other ethnic groups. Clinical outcome studies have consistently observed that in patients with stage 2 hypertension (defined as SBP of 160 to 179 mm Hg or DBP >100 to 109 mm Hg by the International Society of Hypertension), pharmacologically lowering BP is associated with a reduction in adverse cardiovascular events. Proportionally larger reductions in CVD adverse events also occur with greater reductions in BP, with no clear overall differences in outcomes based on the particular pharmacologic agent used. In the SPRINT trial, which enrolled older subjects with CVD or at high CVD risk and an SBP between 130 mm Hg and 180 mm Hg (with mean enrollment BP of approximately 140/78 mm Hg), intensive BP treatment (to a target SBP <120 mm Hg) reduced cardiovascular events compared with standard BP treatment to an SBP of less than 140 mm Hg. Mean SBP was 122 mm Hg in the intensive-treatment group compared with 134 mm Hg in the standard-treatment group, and although intensive treatment was associated with better cardiovascular outcomes, this required an average of three different drugs in these individuals, and there were more side effects (including acute kidney injury and syncope). The large benefits observed in SPRINT are somewhat tempered by results of other studies, such as the ACCORD study in diabetics, where similar reductions in BP with intensive treatment compared with standard management (119 mm Hg versus 134 mm Hg) resulted in a 41% reduction in stroke risk, but not in overall adverse CV events. Furthermore, the recent HOPE-3 study found that in intermediate CVD risk individuals, pharmacologic blood pressure lowering only reduced major CVD events in those with a baseline systolic BP > 143 mm Hg, with no benefit in lower BP ranges.
Based on current data, antihypertensive therapy should be strongly recommended for those with stage 1 or 2 hypertension (e.g., a BP > 140/90 mm Hg). In patients at otherwise low cardiovascular risk, a BP of less than 140/90 mm Hg is an acceptable target with pharmacologic therapy. In patients with diabetes, lower treatment targets (e.g., <130/80 mm Hg) may be considered because of its potential benefit for reducing stroke risk; and in patients with established CVD or at high risk of CVD development, intensive BP treatment to an SBP target of 120 mm Hg can be considered if the therapies are well tolerated.
Choice of Pharmacotherapy
In some ethnic groups it has been shown that certain antihypertensive agents are less efficacious (e.g., angiotensin converting enzyme inhibitors in Africans), however there are no studies that report different pharmacologic effects in South Asians. Therefore, any first line antihypertensive drugs can be considered for the treatment of hypertension. Greater BP reduction is achievable using low doses of combinations of two or three antihypertensive agents compared with standard doses of a single agent, and should be the preferred approach in most individuals when initiating pharmacologic therapy.
Two studies in Indian participants have evaluated combination BP and cholesterol reduction using fixed dose combination therapy with a polypill (ie, Polycap) containing hydrochlorothiazide (12.5 mg), atenolol (25 mg), Ramipril (5 mg), simvastatin (20 mg) and aspirin (75 mg). In a 12-week, multiple comparison, randomized control trial comparing once-daily Polycap with its individual pharmacologic components it was reported that Polycap reduced SBP by 7.4 mm Hg and DBP by 5.6 mm Hg. This was significantly larger than the effects of any one BP lowering drug, and similar to the effect of all three BP lowering drugs given separately. In fact, in participants with baseline hypertension, the number of antihypertensive pills taken was significantly associated with the achievement of better BP control ( Fig. 4.2 ). Side-effects and discontinuation rates were similar to groups that received only one of the component drugs. A second clinical trial compared low dose with high-dose Polycap in 518 South Asian participants, and found that the high dose regimen further reduced BP by 25%, with similar discontinuation rates. The use of a polypill has several potential benefits for hypertension management in low- and lower-middle-income countries. Firstly, larger BP reductions are achievable using combination antihypertensive treatment, which will result in a greater proportion of patients with hypertension achieving adequate BP control. Secondly, reductions in both BP and serum cholesterol can be achieved with a single pill, allowing for better optimization of vascular risk factors with a simplified regimen that can be applied to a broad range of socioeconomic settings. Finally, using inexpensive components, a polypill can be marketed at a very low cost, which is of particular benefit in countries (including those in South Asia) where affordability remains a significant barrier to medication use.
