Matthew Schumaecker, MD, FACC
ASH Designated Specialist in Clinical Hypertension
Carilion Clinic
Assistant Professor of Medicine
VTC School of Medicine
http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
NHANES Hypertension Prevalence
US Adults; 2003-2010
Hypertension
30.4%
Controlled
46.5%
Uncontrolled
53.5%
Aware and
treated
44.8%
CDC MMWR 2012; 61(35);703-709
Aware and
untreated
15.8%
Unaware
39.4%
Hypertension Causes CHF
Circulation 2002;106:3068-3072
Hypertension Causes Stroke
Lancet 361(9362) 2003; p1060
PROSPECTIVE STUDIES COLLABORATION
Hypertension Causes CAD
Lancet 361(9362) 2003; p1060
PROSPECTIVE STUDIES COLLABORATION
Hypertension Causes CAD
MRFIT Arch Intern Med 1993;153:186-208 via KCH
Hypertension Causes Kidney Disease
Incidence of ESRD by SBP in x/100,000 person-years
Klag MJ et al JAMA 1997;277:1293
Defining Hypertension
“There is no dividing line. The relationship
between arterial pressure and mortality is
quantitative – the higher the pressure, the
worse the prognosis”
Sir George Pickering
Guideline Definitions
BP
British GL
European
AHA 2013
“JNC 8”
Definition of
Hypertension
≥140/90
or ABPM ≥135/90
≥140/90
≥140/90
Not defined
Threshold for drug
therapy
≥160/100
or ABPM ≥150/95
≥140/90
≥140/90
<60 y ≥140/90
≥60 y 150/90
BP targets
<140/90
≥80 y < 150/90
<140/90
≥80 y SBP < 150
<140/90
<140/90
≥60 y < 150/90
Pathophysiology of Hypertension
• Four major systems
– Renal
– Vascular
– Autonomic Nervous
– Endocrine
(heart plays very little role in etiology of HTN)
Problems in Understanding
Pathogenesis
• Much of our data is from rodent models
• Hypertension is not considered to be one
disease entity
– Systolic hypertension in young adults
– Diastolic hypertension in middle age
– Isolated systolic hypertension in advanced age
Neural Mechanisms
Baroreceptors
• Receptors that mediate increase in CO and
SVR in response to a fall in BP via the NTS
• Play a role in carotid hypersensitivity
• Pacing the carotid baroreceptors has been
shown to reduce BP
Neuro-Renal Mechanisms
• Renal sympathetic nerve activity
– Causes renin release
– Causes renal vasoconstriction
– Enhances renal sodium and water reaborption
Peripheral Sympathetic Overactivity
• Usually the culprit in young
patients with systolic
hypertension
• Thought to be behind the white
coat hypertension phenomenon
• Should (but frequently doesn’t)
respond to beta blockers
Renal Mechanisms
• Salt Hypothesis
• Intra-renal RAAS
• Renal medullary endothelin
Pressure-Diuresis Relationship
Resetting of Pressure-Diuresis
Vascular Mechanisms
• Endothelial dysfunction
• Chronic vascular inflammation
• Large vessel stiffness
Hormonal Mechanisms
• Renin-Angiotensin-Aldosterone
• Inherited and acquired endocrinopathies
– Cushing’s Disease
– Hyperaldosteronism
– 11βHSD deficiency – AME
– Many others
We All Measure BP Wrong
Kaplan’s Clinical Hypertension 14th Ed
Home BP Monitoring is (Usually) Better
– Multiple studies show that HBPM is a better
prognostic indicator than OBPM
– Should minimize the “white-coat” and “masked” BP
effect
– Best device is upper arm oscillometric device
– Patients have to be instructed:
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No caffeine < 30 min
No smoking < 30 min
Rest 5 min first
No talking
Relax
Use same arm rest on firm surface
Source: escardio.org
Essential Hypertension
• Elevated BP in which secondary causes are not
present.
• 95% of all cases of HTN are essential
• Etiologic causes include:
1.
2.
3.
4.
5.
6.
Obesity
Insulin resistance
Aging
Stress
High sodium intake
Low potassium and calcium intake
Carretero and Oparil Circulation. 2000; 101: 329-335
Pulse Wave Reflection
Effect of Age on Reflected Pulse Wave
Pulse Pressure Increases > 55 years
Hypertension 1995;25:305 -> Kaplan Clinical HTN
Common Causes of
Secondary Hypertension
Endogenous (common)
• OSA
• Primary aldosteronism
• Renovascular hypertension
• Pre-eclampsia
• Hyperparathyroidism
• Vitamin D deficiency
Exogenous
• Obesity
• NSAIDS
• SSRI/SNRI
• Heavy EtOH use
• Epo use in ESRD
• Caffeine(???)
• Nicotine(???)
Less Common Causes of Secondary
Hypertension
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Pheochromocytoma
Acromegaly
Cushing’s Disease
11β-hydroxysteroid2 inhibition
Calcineurin inhibitors
Intracranial pressure
Thyrotoxicosis
Liddle’s Syndrome
Gordon’s Syndrome
Acute porphyria
Familial dysautonomia
Beriberi
Paget’s disease of bone
Burns
Polycystic kidney disease
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Congenital adrenal hyperplasia
Sickle cell crisis
Perioperative
Nicotine(?)
AV fistula
Patent ductus arteriosus
Carcinoid syndrome
Spinal cord injury
Lead poisoning
Guillian-Barré
Preliminary Secondary HTN workup
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Aldo/Renin Ratio (> 30 abnormal)
Plasma renin activity
Calcium levels -> PTH if elevated
Renal duplex
Sleep study
Metanephrines (commonly ordered, rarely
positive)
• Echo in patients with unequal UE/LE BP
Unlike Lipids, There is Abundant
Primary CV Prevention Data
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VA Cooperative Study 1&2
ALLHAT
NHANES III
SHEP
HYVET
HOT
VA Cooperative Trial
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Began in 1964
Reserpine/chlorthalidone/hydralazine
Mean age 49 years
523 men
Stopped after 18 months because of ~ 50% CV
death reduction in treatment arm
SHEP
• 4736 patents > 60 years of age with isolated
systolic hypertension
• (Stepped therapy with chlorthalidone +/atenolol ) vs. (placebo)
• CVA reduction in treatment arm 36%
Syst-Eur
• European version of SHEP done with staged
therapy
• Placebo -> nitrendipine +/ lisinopril +/- HCTZ
vs placebo
• Treatement of 1000 patients for 5 years will
prevent 29 strokes and 53 CV endpoints
• 33,357 patients > 55 years
• Sponsored by NHLBI
• Randomly assigned to
– Chlorthalidone
– Amlodipine
– Lisinopril
– Doxazosin
Doxazosin arm was discontinued because of
doubling of CHF incidence
HOT
Major CV
Events
/1000
pt years
Lancet 1988;351:755
Renal Denervation
http://www.terumo.com/
Symplicity HTN 3
JNC 7 vs ‘JNC 8’
Medical Treatment of HTN
CLONIDINE
HYDRALAZINE
NICE Guidelines
• Similar to JNC Guidelines
• Recommends ACE-ARB for whites
and CCB for blacks prior to diuretic
• Specifically recommends
chlorthalidone or indapamide over
HCTZ
CONCLUSIONS
• We can save more lives by treating hypertension
before it causes target organ damage
• Lowering BP is proven to be good but in the
elderly there may be too much of a ‘good’ thing
• Use diuretics, ACE/ARB and CCB at reasonable
doses before trying anything else
• Spironolactone should likely be fourth line
• Most people do not have secondary hypertension
mmschumaecker@carilionclinic.org
(540) 494-2411