Hypertension

Hypertension in Diabetes Mellitus

Hypertension: The Silent KillerFacts & Figures

50 million Americans & 1 billion worldwide affected

Most common primary care diagnosis (35 million visits annually)

Normotensive at age 55 have 90% lifetime risk of Hypertension

Continuous & consistent relationship with CVD Between ages 40-70, starting from 115/75 CVD risk doubles with each increment of 20/10

Data from King H et al. Diabetes Care. 1998;21:1414-1431.

Top Three Countries for Diabetes

Blood Pressure (mm Hg) Category

Systolic Diastolic

<120 and <80 Normal

120-139 or 80-89 Prehypertension

140-159 or 90-99 Stage 1 hypertension

≥160 or ≥100 Stage 2 hypertension

JNC 7 Definition

Hypertension 2003;42:1206-52

What is Hypertension?

Types of Hypertension

Essential hypertension

90%

No underlying cause

Secondary hypertension

Underlying cause

Causes of Secondary Hypertension

Renal Parenchymal Vascular Others

Endocrine Neurogenic Miscellaneous Unknown

Hypertension: Predisposing factors

Age > 60 years Sex (men and postmenopausal women) Family history of cardiovascular disease Smoking High cholesterol diet Co-existing disorders such as diabetes, obesity and

hyperlipidaemia High intake of alcohol Sedentary life style

National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.

Hypertension: A Significant CV and Renal Disease Risk Factor

CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment*

*Individuals aged 40-69 years, starting at BP 115/75 mm Hg.CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressureLewington S, et al. Lancet. 2002; 60:1903-1913.JNC VII. JAMA. 2003.

CVmortality

risk

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

Pathophysiology of hypertension in DM

The derangements in glucose, lipid, and protein metabolism lead to

functional abnormalities in autonomic nerves

overproduction of vasoconstrictor factors that increase vascular tone

concomitant reductions in the biologic actions of vasodilators

resulting in an increase in BP

Vasoactive substancesCause structural changes in the CV system and in the kidney through effects on:

Vascular smooth muscle cell hypertrophy

Hyperplasia, angiogenesis, cellular apoptosis, macrophage/fibroblast activation with augmented formation of extracellular matrix

Adhesive interactions of circulating leukocytes and platelets with the vessel wall

Processes important in the development or perpetuation of hypertension in diabetics

Alterations in the balanced production of vasodilator & vasoconstrictor substances from the endothelium

Altered vascular smooth muscle responses to these substances

Resistance of peripheral tissues & selected lipid metabolic processes to the actions of insulin

Alterations in the cellular & extracellular elements that comprise the vessel wall

Reactive oxygen species (ROS)

Diabetics—increased metabolic processes that produce reactive oxygen species (ROS)

ROS serve as signaling mechanisms mediate many of the functional & structural vascular abnormalities observed in diabetics

Thus, hypertension in diabetics probably results from a series of interrelated, complex functional and structural abnormalities

Management: JNC 7 GUIDELINES

What are the goals of therapy?

<140/90 for patients without diabetes or renal disease

Most patients who achieve their systolic goal will also achieve their diastolic goal

<130/80 for patients with diabetes or renal disease

JNC VII Guidelines

But… There are Reasons for Inadequate BP Control

Poor compliance to lifestyle modifications

Acceptance of inadequate control by physician

Difficulty achieving BP control with one agent/suboptimal regimens

BP goals are more aggressive than in previous years

Lack of compliance due to: Perceived side effects of antihypertensive medication(s) Frequency of dosing/multiple agents to attain control

JNC VI. Arch Intern Med. 1997

And that leads to…

Refractory hypertension –

Defined by a blood pressure of at least 140/90 or at least 130/80

in patients with diabetes or renal disease despite adherence to

treatment with full doses of at least three antihypertensive

medications, including a diuretic.

JNC VII Guidelines

Refractory hypertension is primarily a systolic and age related problem

It affects 5-30% of the general population with hypertension

Patients with refractory hypertension have an increased risk of Stroke, Aortic Dissecting Aneurysm, Myocardial Infarction, Congestive Heart Failure and Renal failure compared to other hypertensive patients

J Hypertens. 2005;23(8):1441-4, Hypertension. 1988;11(3 Pt 2):II71-5, Minerva Med. 2003;94(4):201-14.

Refractory Hypertension leads to

Causes of Refractory Hypertension

The main reasons why hypertension may be unresponsive to a standard antihypertensive treatment include:

Incorrect diagnosis, Secondary forms of hypertension, Inadequate antihypertensive drug regimen, Associated factors or diseases, Use of non-steroidal anti-inflammatory drugs, Non-compliance with antihypertensive treatment.

Although non-compliance may also be common in patients with well-controlled blood pressure, poor compliance with drug treatment is generally recognized as a major cause of unsatisfactory blood pressure control.

Approach to Resistant Hypertension

Establish “true resistance”

Measure BP accurately

Consider “White Coat Hypertension”

Consider “Pseudoresistance”

Medication Adherence

Consider secondary causes

Accurate BP Measurement

“Persons should be seated quietly for 5 minutes with feet on the floor and the arm supported at heart level”

Cuff must be appropriately sized (cuff bladder must encircle 80% of the arm)

Check both arms and a leg (or palpate pulses carefully)

Caffeine and Tobacco can transiently raise BP substantially

White Coat Hypertension

20-30% of Apparently Resistant Hypertension May be due to “White-Coat Hypertension”

Patients with WCH have an increased risk of CV events and often have some degree of end organ damage

Use home or ambulatory monitoring to sort out

Pseudoresistance

Pseudohypertension

Non-adherence may account for up to 50% of resistant cases

Inadequate Regimen Especially inadequate diuretic component

Interfering medicines and substances also need to be considered NSAIDs Excessive Alcohol, Caffeine, or Tobacco Excessive Salt Intake Drugs of Abuse Oral contraceptives

The Importance of Adherence

Only 1/2 to 2/3 of patients take at least 75% of prescribed antihypertensive medicines1

Of those taking < 75%, only 37% achieved BP goal Of those taking ≥ 75%, 81% achieved goal

In a recent BMJ study, the same rate of adherence was found in both responsive and resistant patients (82%)2

1. Arch Int Med 1987; 147:1393-1396

2. BMJ 2001; 323:142

Techniques to Improve Adherence

Education of the patient Increases awareness but less effect on behavior

Minimize the number of pills Combination pills (ACEI/Diuretic, ARB/Diuretic, ARB/Ca-

blocker, etc.)

Increase the frequency of visits Use of care managers

Secondary Causes of Hypertension

Obstructive Sleep Apnea

Obesity (Metabolic Syndrome)

Endocrinopathies Hyperaldosteronism, thyroid problems,

pheochromocytoma

Kidney Disease Renal Insufficiency and Renal Artery Stenosis

Management of Refractory Hypertension

Management of Refractory Hypertension - 1 The therapeutic outline should be optimized with the different classes of

antihypertensives, including the use of a diuretic in adequate therapeutic doses.

Two different strategies can be used in the attempt of finding an appropriate therapeutic outline for each patient, besides basing it on pathophysiologic knowledge: 1) The empiric approach based on the systematic changes of antihypertensive drugs with the use of associations of two, three or four different pharmacological classes together with adequate dose of thiazide diuretics. The use of loop diuretics follows the same orientation applied to hypertension of other degrees.

2) The rational approach considering the hemodynamic profile and the levels of activity of plasma renin allows to divide this group of patients into volume-dependent and renin-dependent, making it possible to better choose the antihypertensive for each subgroup.

Prevalence of high hyperactivity found in young hypertensive patients and elevation of the levels of activity of renin guide the preferential use of beta-blockers in association with thiazides.

N Engl J Med. 2001;344(1):3-10, Med. 2000;107(5):57-70.

Management of Refractory Hypertension - II

If available, the quantification of plasma renin can address the treatment with drugs.

If the patient presents high plasma renin activity (>0.65 ng/mL/h), the treatment begins with angiotensin converting enzyme (ACEI), AT1 angiotensin II receptor blockers and beta-blockers.

If the plasma renin activity becomes low (<0.65 ng/mL/h), the patient is classified as volume-dependent and should be treated preferentially with a diuretic and calcium channels blockers.

Management of Refractory Hypertension - III

Central nervous alpha-blockers (prazosin, doxazosin, alpha-

metildopa and clonidine), direct vasodilators (hydralazine

and minoxidil) may be used in resistant hypertension when

association with other drugs fails.

In patients with high plasma aldosterone, the associated

use of mineralocorticoid antagonists (spironolactone and

eplerenone) can be effective to reduce the blood pressure

besides delaying the structural alterations that characterize

the cardiovascular remodeling.

Study performed at Mayo Clinics with Refractory Hypertensive patients

A study performed at Mayo Clinics (US) with 104 refractory

hypertensive patients demonstrated that there was a control of

blood pressure and reduction in vascular resistance when the

pharmacological treatment was based on hemodynamic non-

invasive measurements (thoracic bioimpedance) when compared

with the empiric choice of classes of antihypertensives and

adjustments of doses to the specialist's criterion regarding arterial

hypertension.

Hypertension. 2002;39(5):982-8.

Thank You

Hypertension

Health & Medicine

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