Hypertension



Hypertension


Phuong-Mai T. Pham

Phuong-Anh T. Pham

Son V. Pham

Cynthia C. Nast

Hai V. Pham



DEFINITIONS/GENERAL CONCEPTS


Epidemiology



  • Worldwide trends in blood pressure (BP) from 1975 to 2015 based on pooled analysis of 1,479 population-based measurement studies with 19.1 million participants:



    • Global age-standardized prevalence of hypertension (HTN), defined as systolic blood pressure (SBP) >140/90 mm Hg, was 24% in men and 20% in women in 2015.


    • The number of people with HTN has increased by 90% during the four decades studied, presumably due to population growth and aging.


    • Prevalence of HTN decreased in high-income, increased in low-income countries in South Asia and Sub-Saharan Africa, and remains persistently high in Central and Eastern Europe.


HTN in the United States (Centers for Disease control and Prevention 2020)



  • Over 100 million have HTN, defined as SBP ≥130 mm Hg or diastolic blood pressure (DBP) ≥80 mm Hg, or are taking antihypertensive medications.


  • Half of adults with BP ≥140/90 mm Hg who should be taking antihypertensives are not prescribed or taking the medication.


  • Only about one in four adults have their HTN under control.


  • HTN costs the United States approximately $131 billion annually, averaged from 2003 to 2014.


  • Geographic prevalence: HTN is most prevalent in the southeast and eastern urban regions of the United States.


  • HTN by gender: 47% of men and 43% of women have HTN.


  • HTN by race: 54% in non-Hispanic black adults, 46% in non-Hispanic white adults, 39% in non-Hispanic Asian adults, and 36% in Hispanic adults


  • Among those recommended to take antihypertensive medications, BP control is seen in 32% of non-Hispanic white adults, 25% in non-Hispanic black adults, 19% in non-Hispanic Asian adults, and 25% in Hispanic adults.


BP Measurements



  • Standardized office or home BP measuring techniques: (1) no conversation; (2) no exercise, nicotine, or caffeine at least 30 minutes prior; (3) empty bladder; (4)
    place correct cuff size on bare arm; (5) support arm at heart level; (6) keep legs uncrossed; (7) support back and feet


  • For automated oscillometric BP (AOBP) office measurements: after 5-minute rest, average two to five measurements at intervals of 1 to 2 minutes


  • Variability in BP measurements:



    • Casual office BP (defined as not following standardized techniques outlined above) is generally 5 to 10 mm Hg higher than standardized office or home BP, AOBP, and awake ambulatory BP.


    • Standardized office BP may be lower than awake ambulatory BP.


  • Out-of-office BP may provide better prediction of kidney disease progression and cardiovascular (CV) events than in-office BP measurements among patients with chronic kidney disease (CKD).


  • Between-arm BP measurement differences:



    • Between-arm BP differences of 4 to 5 mm Hg occur in healthy individuals.


    • Values >10 mm Hg should be considered for vascular assessment.


    • Values >15 mm Hg is a predictor of prevalent vascular disease and death.


    • BP treatment should be based on higher BP arm.


Indications for Ambulatory BP Measurements



  • Suspected white coat hypertension (WCH) or masked HTN


  • Apparent drug resistance (BP not at goal while seemingly being on maximal and optimal drug combination, WCH, noncompliance, proper BP measuring techniques, etc., have not been ruled out.)


  • Hypotensive symptoms


  • Autonomic dysfunction


  • Episodic HTN


  • Evaluation of nocturnal BP dipper or riser as prognostic factor for target organ damage


  • Evaluation of BP changes in patients with paroxysmal nocturnal dyspnea and nocturnal angina


  • Carotid sinus syncope


  • Pacemaker syndromes


  • Safety of withdrawing antihypertensive medications


  • Assess 24-hour BP control on once-daily medication


  • Borderline HTN with target organ damage


  • Evaluation of antihypertensive drug therapy in clinical trials


BP Categories



  • BP categorization below is based on the average of two or more properly measured readings obtained on at least two separate visits after initial screen.


  • Adults >18 years of age:



    • Normal: SBP < 120 mm Hg and DBP < 80 mm Hg


    • *Elevated BP:



      • SBP 120 to 129 mm Hg and DBP < 80 mm Hg


      • *Pre-HTN category is no longer used.


    • Stage 1: 130 to 139 mm Hg or DBP 80 to 89 mm Hg


    • Stage 2: SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg



    • HTN based on ambulatory BP monitoring:



      • 24-hour average > 130/80 mm Hg


      • Daytime (awake) average > 135/85 mm Hg


      • Nighttime (asleep) average > 120/70 mm Hg


  • Categorization of HTN in pregnancy is defined in Pregnancy and HTN section.


BP Goals



  • 2017 Hypertension Clinical Practice Guidelines of the American College of Cardiology/American Heart Association (ACC/AHA):



    • The 2017 Hypertension Clinical Practice Guidelines relies on average BP readings.


    • BP should be categorized as normal, elevated, or stage 1 or 2 HTN.


    • Out-of-office BP measurements are recommended to confirm the diagnosis of HTN and titrate BP-lowering medication.


    • Goal BP for everyone is <130/80 mm Hg, except:



      • Older adults ≥65 years old with HTN and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/benefit are reasonable for decisions regarding intensity of BP-lowering and choice of antihypertensive drugs.


Management


General management regardless of BP level



Addition of pharmacologic therapy is recommended for



  • HTN stage 2 (average SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg) or


  • HTN stage 1 (average SBP 130 to 139 mm Hg or DBP 80 to 89 mm Hg) if:



    • Known atherosclerotic cardiovascular disease (ASCVD) or 10-year risk ≥10%


    • Diabetes mellitus (DM) type 2, or


    • CKD



Special considerations



  • For patients with asymptomatic mild or moderate aortic stenosis with normal left ventricular systolic function: BP target of 130-139/70-89 mm Hg is reasonable. A post hoc analysis of the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial revealed the lowest all-cause mortality rate for patients in the BP range of 120-139/70-79 mm Hg. All-cause mortality was significantly associated with average SBP < 120 mm Hg and average DBP ≥ 90 mm Hg.


  • For patients >65 years old, be cautious not to lower DBP <65 mm Hg because this has been suggested to be associated with increased stroke risk.


Types of HTN


White coat hypertension (WCH)



  • Definition: having home or daytime ambulatory SBP < 130/80 mm Hg but office BP > 130/80 mm Hg after 3 months of diet and lifestyle modification


  • Prevalence among patients with CKD has been estimated to range from 2% to 41%.



  • Clinical significance of WCH:



    • Some studies revealed increased left ventricular mass index compared to individuals with normal BP.


    • Affected individuals may have impaired diastolic function and higher levels of catecholamines, renin/aldosterone, low-density lipoproteins.


    • Conversion to sustained HTN occurs in 1% to 5% annually.


  • Start antihypertensive if office BP is persistently elevated with evidence of target organ damage.


Masked HTN



  • Definition: BP measured in the office is lower than that measured in the out-of-office setting (opposite of WCH).


  • Prevalence in the general population is estimated at 10% to 20% and higher at 20% to 50%+ in patients with CKD.


  • A systemic review of published literature from 2000 to 2018 reported similar risks of fatal and nonfatal cardiac and CV events among patients with masked HTN compared with those with sustained HTN (hazard ratio [HR] ˜2.1 vs. 2.3).


  • Initiate antihypertensive therapy if elevated 24-hour ambulatory BP and evidence of target organ damage.


Sustained HTN



  • HTN in both in-office and out-of-office settings


Pseudo-HTN



  • Cuff BP is higher when compared with intra-arterial pressure because of excessive atheromatosis and/or medial hypertrophy in arterial tree.


  • May be diagnosed by Osler maneuver:



    • Inflate BP cuff above SBP (detected by loss of pulse with auscultation). Osler maneuver is positive when either brachial or radial artery remains palpable despite loss of pulse by auscultation.


    • Pseudo-HTN is defined as cuff-measured DBP >10 to 15 mm Hg compared with that of intra-arterial measurement.


    • Management of BP should be based on intra-arterial value.


Isolated systolic hypertension (ISH)



  • Occurs with stiffening of large arteries leading to reduced vessel capacitance and acceleration of pulse wave velocity, hence widening of pulse pressure


  • Increase in SBP continues throughout life, in contrast to DBP, which increases and peaks by age of 50 and then decreases later in life.


  • After 50 years, SBP is more important than DBP.


Isolated diastolic hypertension (IDH)



  • IDH is defined as having DBP ≥ 80 mm Hg with SBP <130 mm Hg (per 2017 ACC/AHA)


  • More common among young men, individuals with sedentary lifestyle, overweight/obesity


  • IDH is more common than combined systolic and diastolic HTN (SDH) and ISH in individuals <40 years of age. IDH is rare in individuals >60 years old.



Clinical significance of IDH is unclear



  • Rate of progression or conversion to SDH noted to be 55% in 6.7 years in Framingham Heart Study.


  • Finland study involving 3,267 healthy men aged 32 to 45 years with untreated IDH had no increase in all-cause mortality.


  • Cross-sectional analyses of the National Health and Nutrition Examination Survey (NHANES 2013 to 2016) and longitudinal analyses of the Atherosclerosis Risk in Communities Study revealed no significant association between IDH and increased risk for CV outcomes.


Management of IDH



  • Focus on salt restriction and weight loss, the latter if overweight or obese


  • Pharmacologic antihypertensive therapy if end-organ damage, that is, proteinuria or left ventricular HTN on electrocardiogram (ECG), or hypothyroidism. Hypothyroidism is associated with BP rise that is more pronounced with DBP than SBP.


  • If no specific indication for any antihypertensive class, IDH patients tend to respond well with just one agent, typically better with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) than dihydropyridine calcium channel blocker (CCB).


Drug-resistant HTN



  • BP is not at goal despite optimal doses (optimal dose, defined as >50% of maximal dose recommended for treatment of HTN) of three different appropriate antihypertensive drug classes, ideally one class being a diuretic.


  • Alternatively, BP is at goal with optimal doses of four appropriate antihypertensive drug classes, ideally once class being a diuretic.


Refractory HTN



  • BP not controlled despite being on ≥5 drugs including a diuretic.


Apparent (drug)-resistant HTN



  • Patients with apparent “drug-resistant HTN” are those who meet criteria above but have not been ruled out for proper BP techniques, WCH, noncompliance, improper BP medication regimens.


Pseudoresistant HTN



  • Patients who initially meet criteria for “drug-resistant HTN” but later proven to fail meeting the same criteria following proper BP measuring techniques, ambulatory BP measurements, and/or compliance with proper BP medication regimens

Apparent resistant HTN may be seen in 15% of the population treated for HTN in the United States. However, ˜50% of whom have pseudoresistant HTN. True resistant HTN is approximated at 5% of treated hypertensives.



Other Definitions


Hypertensive urgency



  • Severe HTN, typically, SBP > 180 mm Hg or DBP >110 mm Hg, in patients with or without symptoms such as severe headaches, dyspnea, or anxiety, but without ongoing end-organ damage



Hypertensive emergency



  • Severe HTN, typically, SBP > 180 mm Hg or DBP >110 mm Hg, in symptomatic patients (e.g., severe headaches, chest pain, neurologic deficits) with ongoing end-organ damage


Dippers and risers



  • Definitions:



    • Dippers are individuals who experience a physiologic nocturnal fall in BP of >10% compared with daytime BP.


    • Risers experience a physiologic nocturnal increase in BP of >10% compared with daytime BP.


  • It has been suggested that nondippers or risers, particularly in association with elevated absolute nighttime BP, may predict end-organ damage and adverse CV events.


  • The proportion of dippers decreases with increasing CKD stage.


  • The proportion of risers increases with increasing CKD stage.


END-ORGAN DAMAGE OF HTN


Kidney Injury


Acute hypertensive nephropathy associated with hypertensive emergencies


Clinical manifestations



  • Hematuria, acute kidney injury (AKI)


Pathogenesis



  • Direct endothelial damage, ischemic injury, microangiopathic hemolytic anemia causing obstruction of interlobular arteries


Histopathology (Fig. 5.1)



  • Fibrinoid necrosis of small arterioles (pink, amorphous fibrinoid materials within vessel wall due to necrosis) and “onion skinning” of small renal arteries. “Onion skinning” is used to describe hyperplastic arteriosclerosis with thickened concentric smooth muscle cell layer with thickened, duplicated basement membrane and narrowed lumen. In malignant HTN, these hyperplastic changes may be accompanied by fibrinoid necrosis of the arterial intima and media.


Chronic hypertensive nephropathy


Clinical manifestations



  • Slowly progressive kidney injury with relatively bland urine, mild albuminuria


  • End-stage kidney disease (ESKD) due solely to HTN is uncommon due to the relative preservation of glomerular injury until advanced stage, except for genetically susceptible subpopulation such as African Americans or those who suffer from frequent hypertensive emergency episodes and associated acute hypertensive nephrosclerosis. The relative glomerular sparing is consistent with the minimal albuminuria associated with chronic hypertensive nephropathy.


Histopathology



  • Slowly progressive thickening and sclerosis of renal resistance vessels with relative sparing of glomerular capillaries. Ischemic glomerular loss occurs slowly over decades.







FIGURE 5.1 Accelerated/malignant hypertension/hypertensive renal emergency. A. Small artery and arteriole show mucoid intimal thickening, endothelial cell swelling, and severe luminal narrowing. Note fibrin (arrow) in the arteriolar intima and glomerular ischemic capillary wall corrugation (Masson’s trichrome ×250). B. Small artery with “onion-skin” pattern thickening of the muscularis and luminal thrombosis (Masson’s trichrome ×400).


Cardiovascular


Acute cardiac complications associated with hypertensive emergencies



  • Acute coronary syndrome, acute myocardial infarction (MI)


  • Acute left ventricular dysfunction, acute heart failure (HF)


  • Acute aortic dissection (see Hypertensive Emergencies section)



Chronic cardiac complications



  • Left ventricular hypertrophy (LVH) that increases the risk of MI, HF, ventricular arrhythmias, sudden cardiac death


  • Diastolic dysfunction


  • HTN is a major risk factor for premature cardiovascular disease (CVD).



  • In older patients, SBP and pulse pressure are better determinants of CVD risk than DBP. (Recall that DBP decreases after age 50.)


Cerebrovascular


Acute



  • Ischemic stroke, intracerebral or subarachnoid hemorrhage


Chronic



  • Ischemic stroke, vascular dementia


  • Lacunar infarctions, microhemorrhages, and focal or diffuse white matter lesions may be seen in early hypertensive microangiopathic complications.


Evaluation of HTN


Routine evaluation in patients with HTN



  • Recommended tests: lipid profile, kidney function, urinalysis, fasting blood glucose, hemoglobin A1C, complete blood count, ECG, thyroid-stimulating hormone


  • Optional tests: echocardiogram, uric acid, urine albumin-to-creatinine ratio


Clinical clues that should prompt evaluation for secondary HTN


Age related



  • Onset at age <30 years in nonobese, non-black patients with a negative family history of HTN and no other risk factors for HTN


  • Onset of diastolic HTN in patients ≥ 65 years old


Acute changes in BP



  • Abrupt-onset HTN


  • Exacerbation of previously controlled HTN


HTN severity



  • Drug-induced, drug-resistant, or refractory HTN


  • Malignant or accelerated HTN (e.g., hypertensive urgency or emergency)


  • Target organ damage is out of proportion to the degree of HTN.


Presence of signs/symptoms related to specific hypertensive conditions



  • Unprovoked (absence of diuretic use) or severe hypokalemia (mineralocorticoid excess)


Evaluation of Suspected Secondary HTN



  • Check for proper BP measurement techniques


  • Check for volume overload


  • Presence of obesity


  • Review drug induced and related causes:



    • Inadequate doses


    • Inappropriate antihypertensive medication combinations (e.g., using several vasodilators in a patient with increased heart rate without a β-blocker [BB], using multiple sympatholytic drugs without any vasodilator, or using multiple drugs with reflex salt-retention but without a diuretic)


    • Prescribed drugs:



      • Nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors


      • Oral contraceptives


      • Adrenal steroids







        FIGURE 5.2 Secondary causes of hypertension by organ system and endocrine glands.


      • Glucocorticoids


      • Cyclosporine (CSA) and tacrolimus


      • Antidepressants (monoamine oxidase [MAO] inhibitors)


      • Erythropoiesis-stimulating agents (reduced nitric oxide [NO] synthesis, increased entholin-1)


      • Vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib (downregulate NO expression)


    • Selected over-the-counter dietary supplements and medicines:



      • Sympathomimetics (decongestants, anorectics)


      • Ephedra, ma huang, bitter orange


      • Licorice (including some chewing tobacco)


    • Common drinks/recreational drugs:



      • Caffeine (small and transient increase in BP)


      • Excess alcohol intake


      • Cocaine, amphetamines, methamphetamines, other illicit drugs


    • Medication nonadherence


  • Identify secondary causes of HTN (Fig. 5.2). Important causes of secondary HTN are discussed in Secondary Causes of Hypertension section later in this chapter.


Routine Management of HTN (ACC/AHA 2019)


Best proven nonpharmacologic interventions for prevention and treatment of HTN



  • Weight reduction:



    • Target ideal body weight or aim for a weight loss of at least 1 kg


    • SBP may reduce by 1 mm Hg/kg weight loss.


  • Adopt DASH-like eating plan:



    • Encourage diet rich in fruits, vegetables, whole grains, low-fat dairy products with reduced saturated and total fat


    • SBP may reduce by 8 to 14 mm Hg.


  • Sodium restriction:



    • <1,500 mg/d; aim for ≥1,000 mg/d reduction in most adults


    • SBP may reduce by 2 to 8 mm Hg.



  • Increase potassium intake:



    • 3,500 to 5,000 mg/d unless patient has problems with hyperkalemia


    • SBP may reduce by 4 to 5 mm Hg.


  • Physical activity:



    • Regular aerobic, dynamic resistance, or isometric resistance activity, for example, 30-minute brisk walk daily, most days of week, or 150-min/wk


    • SBP may reduce by 4 to 9 mm Hg.


  • Moderation of alcohol consumption:



    • <2 drinks daily in most men, <1 drink daily in women and lightweight persons


    • SBP may reduce by 2 to 4 mm Hg.


  • For overall CV risk reduction, stop smoking.


Initiate pharmacologic therapy



  • See indications outlined in BP Goals section.


Follow-up



  • Patients with elevated BP or stage 1 HTN not on drug therapy should have their BP reassessed every 3 to 6 months.


  • Patients initiated on antihypertensive medications should be monitored monthly until BP is controlled and stable.


Pharmacologic Therapy for HTN


Initiating pharmacologic therapy



  • Initial drug selection depends on underlying conditions, “compelling indications” (e.g., ACEI/ARB for systolic HF, post-MI, α-blockers for benign prostate hypertrophy, BBs for essential tremors, hyperthyroidism, migraine, atrial fibrillation/flutter with rapid ventricular rates, angina, mineralocorticoid receptor antagonist for hyperaldosteronism, thiazide diuretics for Gordon syndrome or osteoporosis, amiloride for Liddle syndrome).



    • Mainstay therapy for adults with or at risk for CVD includes BBs and/or ACEI or ARB, with subsequent addition of CCB and/or thiazide or thiazide-like diuretics as needed. Loop diuretics should be reserved for severe HF or severe CKD. Mineralocorticoid-receptor antagonists (MRAs), such as spironolactone or eplerenone, may be considered in ischemic HF or resistant HTN.


  • If there is no “compelling indication” for drug selection, first-line antihypertensive drugs include thiazide diuretics, CCBs, ACEIs, or ARBs. (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT] did not show any difference in coronary heart disease or nonfatal MI and stroke between CCB, ACEI, or thiazide diuretics.)


  • For drug-naïve patients with SBP > 20/10 mm Hg above goal, two-drug therapy should be initiated.


Notes regarding thiazide diuretics



  • Clinically available thiazide and thiazide-like diuretics include hydrochlorothiazide (HCTZ), chlorthalidone (CTDN), and indapamide (INDAP).


  • The longer duration of diuretic and antihypertensive action of CTDN and INDAP compared with HCTZ may confer better nighttime BP control: HCTZ (<24 hours), CTDN (24 to 72 hours), INDAP (24 hours+ and 32 hours+ for immediate-release and sustained-release forms, respectively).



  • Clinical data:



    • 2015 meta-analysis involving 14 randomized controlled trials (RCTs) comparing HCTZ versus CTDN and INDAP:



      • CTDN and INDAP reduced SBP by -3.6 and -5.1 mm Hg more than HCTZ, respectively.


      • No differences in metabolic adverse effects were detected.


    • 2.5-mg INDAP reduced stroke by 29% and all CV events by 23% in the Post Stroke Antihypertensive Treatment Study. Perindopril-INDAP combination also reduced CV events in two other placebo-controlled trials.


    • In an observational cohort study, CTDN was associated with lower LVH compared to HCTZ. In another observational cohort analysis (n = 12,866), the percentage risk reduction in CV events from CTDN versus HCTZ was 21%. In network meta-analyses of randomized trials (n = 50,946), CTDN conferred a 25% risk reduction in congestive heart failure (CHF) and CV events compared with HCTZ.


    • Bottom line: CTDN and INDAP reduce SBP more than HCTZ and confer ˜21% risk reduction in CHF and CV events compared with HCTZ.


    • Protection against fracture: The use of thiazide and thiazide-like diuretics has been shown to confer long-term protection against fracture compared to the use of other antihypertensive agents.


    • Use of thiazide diuretics in CKD: CTDN has been shown to remain effective in reducing SBP by 19 to 20 mm Hg even in patients with advanced CKD G4. Continuation of thiazide diuretics rather than switching to loop diuretics may be appropriate in a stable patient if volume overload is not a concern. Loop diuretic switch is reasonable in the case of resistant HTN and/or volume overload.


The use of low-dose MRA (e.g., aldosterone)



  • Confers additional benefits in CV outcomes in patients with New York Heart Association (NYHA) classes III and IV HF or decreased left ventricular ejection fraction after an MI.


  • Recommended to be used concurrently with thiazide diuretics to offset hypokalemia


  • May lower BP regardless of serum aldosterone levels


  • BP-lowering effect has been shown to be more pronounced in patients with suppressed plasma renin activity (PRA).


  • May reduce BP even in hemodialysis patients


  • Recommended to be added in resistant HTN: spironolactone 25 to 50 mg daily. Anglo-Scandinavian Cardiac Outcomes Trial revealed that the addition of spironolactone at median dose of 25 mg daily in addition to 2.9 other antihypertensive medications lead to a fall in BP of 21.9/9.5 mm Hg at 1.3-year follow-up. Optimum Treatment of Drug-Resistant Hypertension Study revealed the addition of spironolactone at 25 to 50 mg every day (qd) over a 12-week treatment period reduced SBP by 8.7 mm Hg on average compared to placebo.


  • Adverse effects: hyperkalemia, metabolic acidosis



Specific drug contraindications



  • ACEI in angioedema (angioedema has also been reported with ARB), BBs with poorly controlled bronchospasm, reserpine in depression, methyldopa in liver disease, ACEI/ARB/or renin inhibitors in pregnancy or pregnancy planning, BBs and nondihydropyridine CCBs in second- or third-degree heart blocks



Special Considerations in Pharmacologic Therapy of HTN


Use of ACEI or ARB should be considered for the following



  • Nondiabetics with HTN and albuminuria ≥30 mg/d


  • Patients with HTN and CKD (including African Americans)


Direct renin inhibitor (DRI) combination with ACEI and ARB


Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) Trial



  • Combination therapy consisting of losartan and aliskiren was minimally beneficial compared to lone losartan therapy in patients with DM type 2 with urine albumin-to-creatinine ratio >300 mg/g.


  • Combination therapy was associated with higher rate of hyperkalemia (4.7% vs. 17%).


Aliskiren in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial



  • Combination therapy with aliskiren and either an ACEI or ARB in patients with diabetic kidney disease reduced proteinuria and SBP by 1 to 2 mm Hg compared with placebo group receiving either ACEI or ARB alone.


  • 25% greater stroke rate and more frequent hyperkalemia were observed with combination therapy.


Weight and antihypertensive therapy



  • The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic HTN (ACCOMPLISH) trial suggests the preferential addition of a CCB over a diuretic to an ACEI in normal weight patients in terms of CV outcome (i.e., [CCB + ACEI] is better than [diuretic + ACEI] in normal weight patients). In obese high-risk hypertensive patients, the choice of adding either a diuretic or CCB to an ACEI is less important.


  • The difference in outcome was thought to be due to the difference in pathogenesis of HTN in normal versus obese patients. Lean individuals may have more prominent renin and sympathetic nervous system (SNS) activities with their HTN and are thus more sensitive to diuretics, which could further stimulate renin-angiotensin-aldosterone system (RAAS).


Antihypertensive therapy based on PRA: “renin profiling”



  • PRA > 0.65 ng/mL/h (typically seen in younger Caucasians) may have HTN associated with vasoconstriction and respond well to ACEI, ARB, or BBs.


  • PRA < 0.65 ng/mL/h (typically seen in African Americans, Afro-Caribbeans, and older Caucasians) may indicate volume expansion-related HTN and may respond well to diuretics and CCB.


  • A 2016 pilot study comparing the effectiveness of adding aldosterone antagonist (AA) versus administering renin-guided therapy (RGT) outlined above to patients with resistant HTN revealed fewer additional medications required for RGT versus AA to achieve the same antihypertensive effect.


Considerations for BP management in African Americans



  • Use of two-drug combination therapy is recommended in most African Americans.


  • For those without HF or CKD who do not meet criteria for two-drug therapy, a thiazide-type diuretic or CCB should be initially treated.


  • For those with HF or CKD, renin-angiotensin system inhibition should be prescribed.



Considerations for BP management in the elderly



  • Cognitive function:



    • Available data do not show cognitive decline in elderly patients who achieve target BP with the use of antihypertensive therapy (Hispanic Community Health Study/Study of Latinos). However, women with uncontrolled BP despite being treated with antihypertensive medications may have an associated cognitive decline (Women’s Health Initiative Memory Study).


    • Intensive vs. Standard Ambulatory Blood Pressure Lowering to Lessen Functional Decline in the Elderly (INFINITY) trial: Among elderly patients with HTN, intensive lowering of ambulatory SBP reduced the development of subcortical white matter disease and nonfatal CV events but did not improve mobility or cognitive function.


  • Caution with frail, institutionalized elderly: BP lowering to < 130/80 mm Hg with the use of two or more antihypertensive agents in older nursing home residents is associated with increased mortality rates (Treatment with Multiple Blood Pressure Medications, Achieved Blood Pressure, and Mortality in Older Nursing Home Residents Study)


Other drug considerations in HTN


Sodium-glucose cotransporter 2 (SGLT2)



  • SGLT2 are expressed in S1 and S2 segments of proximal renal tubule where 90% of glucose reabsorption occurs


  • Inhibition of SGLT2 leads to glucosuria, hence glucose control in diabetics, and weight loss due to glucose-derived calories.


  • Inhibition of SGLT2 also leads to mild BP reduction, presumably via (osmotic) diuretic effect.


Valsartan/sacubitril as an antihypertensive agent



  • Although the combination drug has been shown to confer greater antihypertensive effect compared to ARB alone in elderly patients in a 2019 meta-analysis, safety and efficacy data for its use as an antihypertensive agent in RCTs are lacking. Recommendation for its use as an antihypertensive agent has not been made at the time of this writing.


Summary of Systolic Blood Pressure Intervention Trial (SPRINT)


Multicenter RCT of intensive versus standard BP control



  • 9,361 persons with SBP ≥ 130 mm Hg with CVD risks but without DM were enrolled and randomized to SBP control <120 mm Hg (intensive) or <140 mm Hg (control)


  • Inclusion: age ≥ 50 years with SBP ≥ 130 mm Hg and ≥1 of the following: history of CVD, CKD G3, intermediate to high risk for CVD other than stroke, or age ≥75 years


  • Primary composite outcome was MI, other acute coronary syndromes, HF, or death from CV causes.



Results


Overall



  • At 3.26 mean follow-up years, nondiabetic adults, age ≥50 years at increased CVD risk or with CKD with intense BP control had a 25% reduction in primary combined CV outcome and 27% reduction in mortality.



  • Adverse effects:



    • Hypotensive and syncopal episodes and electrolyte disturbances, but not injurious falls, were more common in the intensive group.


    • Among individuals without CKD at enrollment, estimated glomerular filtration rate (eGFR) decline ≥30% to an eGFR of <60 mL/min/1.73 m2 occurred more frequently in the intensive group (1.21%/year vs. 0.35%/year in the intensive vs. control group).


Women



  • Benefit of intensive BP treatment appeared to be less for women compared with men.


Individuals with CKD at enrollment



  • Intensive group had a lower all-cause mortality (HR 0.72), but not individual components of CVD outcome.


Individuals age ≥ 75 years



  • Relative HR of primary CVD outcome and all-cause mortality were lower with marginal significance in the intensive group.



    • There was no difference in kidney outcome, defined as ≥50% decline in eGFR from baseline or reaching ESKD. Degree of albuminuria, but not incident albuminuria, was lower in the intensive group.


    • Adverse events: There were increased risks for AKI (HR 1.46) and dyskalemias in the intensive group.


  • Individuals age ≥ 75 years old at enrollment:



    • Rates of all-cause mortality (HR 0.67) as well as fatal and nonfatal major CV events were lower in the intensive group.


    • Kidney outcome defined above was higher in the intensive group but statistical significance was not reached due to low event numbers.


    • No difference in serious adverse events


  • Note that BP measurement in Systolic Blood Pressure Intervention Trial (SPRINT) trial was based on automated office BP measurements, which are lower than office BP measurements performed by providers.


PRIMARY (ESSENTIAL) HYPERTENSION


Pathogenesis of primary HTN



  • Increased sympathetic activity and responsiveness


  • Increased angiotensin II (AII) activity and mineralocorticoid excess


Risks of primary HTN



  • Genetics: twofold risk if both parents have HTN


  • Reduced nephron mass due to immature birth, intrauterine developmental abnormality (e.g., maternal drug use, malnutrition), and postnatal disturbances (e.g., malnutrition, infections)


  • Black ethnicity (more common and severe compared to non-blacks)


  • Lifestyle associated: high salt intake, excess alcohol consumption, physical inactivity, vitamin D deficiency. Fructose intake, thus far, not proven to increase HTN risk.


  • Metabolic: dyslipidemia, independent of obesity



Diagnosis of primary HTN



  • Rule out WCH


  • Rule out ingestions of medications/substances that can cause HTN (i.e., caffeine, tobacco smoking, amphetamines, cocaine, sympathomimetics, etc.)


  • Rule out secondary causes as per risks, signs/symptoms. See Secondary Causes of HTN section.


  • Routine testing:



    • Full history and physical examination


    • Laboratory studies: See Evaluation of HTN section.


    • In stage 1 HTN, consider microalbuminuria evaluation, ECG, and echocardiogram for determination of antihypertensive therapy initiation.


Management of primary HTN

See Routine Management of HTN section.


SECONDARY HYPERTENSION


Indications for evaluation of secondary HTN


Difficult-to-treat HTN



  • Not controlled on an appropriate combination of three antihypertensive agents of different classes, one of which is a diuretic or


  • Controlled on an appropriate combination of four antihypertensive agents of different classes, one of which is a diuretic.

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Jul 21, 2021 | Posted by in NEPHROLOGY | Comments Off on Hypertension

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