Community Hypertension and Atherosclerosis Risk
Elevated blood pressure (BP) is considered one of the key risk factors in deaths caused by cardiovascular and renal problems. Despite the increase in awareness about hypertension and the advancements in treatment through the last decades, many patients still suffer from elevated BP while on treatment. This study emphasizes the importance of screening for hypertension as a tool to reduce cardiovascular risk in the community setting.
Resistant Hypertension
The term resistant hypertension is described as BP above target despite the use of antihypertensive drugs. The etiology of resistant hypertension is also linked with obesity, increased renal sodium retention, and increased activity in the renin-angiotensin-aldosterone and sympathetic nervous system.
Apparent Resistant Hypertension (ARH)
The term “apparent resistant hypertension” (ARH) is commonly used in the absence of confirmatory out-of-office BP measurements or in the absence of ascertained adherence to the antihypertensive drug treatments. Apparent resistant hypertension is also linked with cardiovascular risk factors and with prevalent cardiovascular disease. Studies have shown that ARH is also an indicator of increased risk for cardiovascular morbidity and mortality.
In 2018, the American College of Cardiology/American Heart Association lowered both the diagnostic threshold and the BP treatment goal for hypertension (140/90 mmHg to 130/80 mmHg). As a result, the prevalence of ARH increases when the lower threshold is applied, but the long-term prognostic impact of ARH diagnosed with the lower blood pressure threshold has not been investigated in a primary preventive setting. The cardiovascular prognosis in patients who change hypertension categories if the more stringent BP criteria are applied is also not known.
The Study
This study analyzes the prevalence and prognostic significance of ARH, diagnosed with either the traditional (BP≥140/90 mmHg) or the more stringent (BP≥130/80 mmHg) criteria, in a community-based cohort of persons without known cardiovascular disease. The researchers showed the cardiovascular outcomes in participants who changed hypertension categories if the hypertension criteria were changed, and the prognostic significance of the number of antihypertensive drug classes use. The participants in the study were mostly Caucasian and African American men and women between 45-64 years of age. They are from four of these US communities (Forsyth County, NC; Jackson, MS; Minneapolis, MN, and Washington County, MD).
The study protocol was approved by the institutional review boards of all participating centers. All participants submitted their written informed consent. Recruitment and enrollment took place between 1987 and 1989, and participants were thereafter followed up prospectively on triennial follow-up visits from 1996-to 1998.
Methods
The researchers first excluded participants with a prevalent or prior diagnosis of (or missing data for) coronary heart disease (n = 699) and/or stroke (n = 298) and/or heart failure (n = 846), participants who were enrolled in the randomized trial ALLHAT(Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) (n = 56) or who had missing data (n = 15) for baseline BP.
The researchers thereafter excluded 401 participants who had incomplete baseline data for one or more of the following variables: BMI (body mass index), heart rate, smoking status, eGFR (estimated glomerular filtration rate), LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol, TG (triglycerides), or prevalent diabetes status (defined as fasting plasma glucose ≥126 mg/dl, non-fasting glucose ≥200 mg/dl, self-reported use of diabetes medications, or self-reported physician diagnosis of diabetes), and those who were of a race other than Black or White or who were non-White participants at the Minneapolis or Washington County Centers. The study cohort ended with 9612 participants.
The following drug classes were identified as antihypertensives: angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcium channel blockers, diuretics (thiazides/thiazide-like diuretics/loop diuretics/potassium-sparing diuretics), beta-adrenergic blockers, mineralocorticoid receptor antagonists (spironolactone), alpha-adrenergic blockers, centrally acting sympatholytics (clonidine/reserpine/methyldopa/guanfacine), and vasodilators (hydralazine/minoxidil). Single-pill combinations were categorized into their component classes. The number of antihypertensive drug classes was summed for each participant.
Results
Regardless of whether the BP goal was <140/90 mmHg or <130/80 mmHg, participants with ARH were less likely to be current smokers, more likely to be Black and to have diabetes, and were on average older, with lower levels of eGFR and HDL and higher levels of TG.
Overall, 3473/9612 participants (36.1%) used ≥1 antihypertensive drug. The four most frequently used antihypertensive drug classes were diuretics, (n = 1507, 43.4% of the treated), followed by calcium channel blockers (n = 1025, 29.5% of the treated), ACE inhibitors or angiotensin receptor blockers (n = 1013, 29.2% of the treated), and beta-adrenergic blockers (n = 1008, 29.0% of the treated).
There were 2096 participants (60.4% of the treated) who used antihypertensive medications from only one drug class, 1075 participants (31.0% of the treated) who used antihypertensive medications from two drug classes, and 302 participants (8.7% of the treated) who used antihypertensive medications from ≥3 drug classes.
The drug class most frequently used as monotherapy was diuretics (n = 505 participants, 24.1% of monotherapy participants).FIGURE 1 Study flowchart. ARIC, atherosclerosis risk in communities; ALLHAT, antihypertensive and lipid-lowering treatment to prevent heart attack trial; BMI, body mass index; CHD, coronary heart disease; eGFR; estimated glomerular filtration rate; HDL, high-density lipoprotein; HF, heart failure; MI, myocardial infarction; LDL, low-density lipoprotein; TG, triglycerides
There were 6139 (63.9%) participants who did not use antihypertensive medications. Among them, the majority (n = 5029, 81.9% of the untreated) had BP <140/90 mmHg (no hypertension), and the remaining 1110 participants (18.1% of the untreated) had BP ≥140/90 mmHg (untreated hypertension). If the more stringent hypertension criteria ≥130/80 mmHg were instead applied, 1172 participants (19.1% of the untreated) were reclassified from no hypertension to untreated hypertension.
There were a total of 3473 participants (36.1%) who used ≥1 antihypertensive medication at baseline. Applying the traditional blood pressure goal of <140/90 mmHg, the number of participants with controlled hypertension was 2306 (66.4% of the treated), 1034 participants (29.8% of the treated) had uncontrolled hypertension and 133 participants (3.8% of the treated) fulfilled the criteria for ARH.
If the more stringent blood pressure goal <130/80 mmHg was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to either uncontrolled hypertension (n = 725, 20.9% of the treated) or to ARH (n = 60, 1.7% of the treated) so that the number of participants with controlled hypertension decreased to 1521 (43.8% of the treated), the number of participants with uncontrolled hypertension increased to 1759 (50.6% of the treated) and the number of participants with ARH increased to 193 (5.6% of the treated).
Conclusion
The study shows that in the observational group who were free from cardiovascular disease at baseline, the long-term risk was higher in participants with ARH, regardless of whether the traditional or the more stringent blood pressure criteria were applied. The increased risk was independent of traditional markers of risk. The risk increased also with higher numbers of antihypertensive medications in patients with blood pressure below either the traditional or the more stringent blood pressure goal.
This simply means that resistance to antihypertensive medications is important in the identification of patients at risk for developing cardiovascular disease. This also suggests that risk factor modification is considered in these patients.
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