Hypertension

Cardiometabolic risk refers to an individual’s probability of developing type 2 diabetes and cardiovascular disease (CVD) due to the presence of “traditional” risk factors and emerging markers [1-3]. These risk factors include age, sex, blood pressure (BP), diabetes (hyperglycemia), smoking, LDL cholesterol, HDL cholesterol, and features of the metabolic syndrome. These features are most often found in individuals with overweight/obesity (particularly abdominal obesity), insulin resistance, atherogenic dyslipidemia, and a pro-thrombotic, inflammatory state [1,2]. As an indicator of global CVD risk, cardiometabolic risk includes traditional risk factors while taking into account the potential contribution of visceral obesity and/or insulin resistance and related metabolic markers (Figure 1) [1-3].

Hypertension is a potent and modifiable CVD risk factor [4,5]. The relationship between BP and CVD risk is linear, consistent, and independent of other risk factors. For instance, the probability of myocardial infarction, heart failure, chronic kidney disease, and stroke rises in step with BP [5]. From a start point of 115/75 mmHg, CVD risk doubles for each 20 mmHg rise in systolic BP and each 10 mmHg rise in diastolic BP [6]. Hypertension-related CVD risk also escalates in the presence of other risk factors [7] (Figure 2).

The classification of BP in adults is based on the average of 2 or more readings taken at each of 2 or more visits [8]. According to the last guidelines [5], BP classification for adults is indicated in the Table. To be considered with normal BP values, systolic BP must be <120 mmHg and diastolic BP must be <80 mmHg. Hypertension is diagnosed when systolic BP values are ≥130 mmHg or when diastolic BP ≥80 mmHg. When individuals have systolic BP values between 120-129 mmHg with normal diastolic BP values, they are classified as being in the elevated category. These patients are at risk of hypertension and CVD and making lifestyle changes is key for them to prevent an eventual progression to hypertension itself [5].

Hypertension may be essential (primary) or secondary. Secondary hypertension has an identifiable cause and accounts for 2% to 10% of cases. Essential hypertension is a diagnosis made in the absence of an identifiable secondary cause. Essential hypertension accounts for approximately 90% to 95% of hypertension cases [9].

The age-adjusted prevalence of hypertension in the United States—defined by a systolic BP ≥130 mmHg and/or a diastolic BP ≥80 mmHg or patients taking antihypertensive medications—is 46% [5]. In Canadian adults, the prevalence of hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or drug treatment) is 22.6% [10]. Of interest is the fact that ethnic origin has an impact on the prevalence of hypertension. Blacks have higher rates of hypertension compared to Caucasians [5]. BP also increases progressively with age (Figure 3) [5,11].

Hypertension triggers an array of cardiovascular damage, such as left ventricular hypertrophy, atrial and ventricular arrhythmias, diastolic heart failure, systolic heart failure, and ischemic heart disease with or without congestive heart failure [9]. Hypertension also harms the central nervous system and kidneys. The presence of other risk factors [7]—such as insulin resistance and the metabolic syndrome [1]—increases hypertension’s harmful impact on target organs and CVD risk.

Obesity has many damaging effects on physiological processes [1,13]. Obesity and hypertension are linked, with obese patients having higher rates of hypertension than normal-weight individuals [14,15]. Interestingly, not every obese patient is hypertensive, indicating that obesity is a heterogeneous condition [16]. Waist circumference has been reported as the strongest independent predictor of systolic BP and diastolic BP in normoglycemic Chinese [17]. Furthermore, excess visceral fat has been found to be associated with hypertension in Japanese Americans [18]. However, hypertension rates were rather high in both studies (56% and 25% respectively) [17,18]. Since some antihypertensive medications may influence insulin sensitivity and the metabolic risk profile over time, it is important to study the relationship of abdominal obesity and BP in population-based cohorts to avoid the influence of confounding factors [19].

In a population-based study—of which only 6.5% of subjects had hypertension—Poirier et al. [20] observed that waist circumference in men and women was most strongly linked to systolic BP and diastolic BP compared to other likely contributors such as insulin resistance and fasting insulin levels. The amount of visceral fat—crudely estimated as waist circumference—may therefore have largely explained the association between obesity, fasting insulin, insulin sensitivity, and BP [20].

Which mechanisms underpin the elevated BP found with visceral obesity independent of insulin resistance? One possible answer lies in the formation of angiotensin II and aldosterone by obesity-induced sympathetic activation and the release of molecules by hypertrophied fat cells. A renin-angiotensin system has also been found in human adipose tissue. Obesity is also known to cause structural alterations in the kidneys that may eventually cause loss of nephron function and a further elevation in BP [21]. Figure 4 illustrates the putative mechanisms of hypertension and CVD in insulin resistance and obesity.

Obesity—abdominal obesity in particular—therefore seems to play an important role in the pathophysiology of hypertension and should not be neglected when determining therapeutic approaches to lowering BP.