Cardiovascular Disorders

HypertensionHypertension is also a significant cause of end stage renal disease and heart failure.

National and international organizations continually refine their recommendations of how clinicians should approach the management of patients with high blood pressure, including • methods of measurement, • patient education, • medication adherence, and • overall benefits of reduced blood pressure.

Selection of drug therapy consequently involves an iterative process of considering multiple antihypertensive drugs as needed • to achieve target blood pressures of less than

140/90 mm Hg for all patients, • with more aggressive targets of less than

130/80 mm Hg for patients with diabetes or chronic kidney disease.

Treatment with drug therapy should be done in combination with recommended lifestyle modifications to manage hypertension and minimize risk.

The prevalence of hypertension differs based on age, sex, and ethnicity

Hypertension is strongly associated with type 2 diabetes. The added comorbidity of hypertension in diabetes leads to a higher risk of cardiovascular disease (CVD), stroke, renal disease, and diabetic retinopathy leading to greater health care costs.

Specific drug selection is guided by the presence of “compelling indications” -specific comorbid conditions.

Compelling indications, suchas heart failure, diabetes, and chronic kidney disease (CKD),represent specific conditions for which explicit evidence in the literature exists to document the utility of a particular agent or class of agents.

In the majority of patients the cause of hypertension is unknown and it is referred to as essential, or primary hypertension.

In some patients there is an identifiable cause e.g. :• Chronic kidney disease• Conctation of the aorta• Cushing’s syndrome and other glucocorticoid excess states• Drug induced/related• Pheochromocytoma• Mineralocorticoid excess states• Renovascular hypertension• Sleep apnea• Thyroid or parathyroid disease

Hypertension caused by any of these conditions is referred to as secondary hypertension.

Identification of a secondary cause of hypertension is often not initially pursued unless suggested by routine clinical and laboratory evaluation of the patient, or failure to achieve blood pressure control.

Another type of hypertension may encounter what is referred to as resistant hypertension: Patients failing to achieve goal blood pressure despite maximum doses of three anti-hypertensives.

Causes of Resistant Hypertension

Factors which are involved in the pathogenesis of hypertension

The pathophysiology of primary hypertension is heterogeneous, but ultimately exerts its effects through the two primary determinants of blood pressure: cardiac output and peripheral resistance.

The processes influencing primary determinants of blood pressure (cardiac output and peripheral resistance) are numerous and complex. The underlying cause of primary hypertension is unknown and most likely multifactorial.

There are several hypotheses for the casue of primary of blood pressure (remember - only a minority of patients with hypertension may have an identifiable cause).

GeneticsMultiple genetic polymorphisms have been associated with hypertension.

It is estimated that up to 30% to 50% of variability in blood pressure may have a genetic basis.

The majority of these polymorphisms appear to be involved directly or indirectly in renal sodium reabsorption.

The identification of genetic factors contributing to variability in response to drug therapy should allow for specific tailoring of individual patient therapy, thereby optimizing the effectiveness of antihypertensive therapy while minimizing costs and adverse events.

The contribution of sodium to the development of primary hypertension is related to excess sodium intake and/or abnormal sodium excretion by the kidneys.

Dietary salt is associated with increases in blood pressure that can be lowered with reduction of sodium intake.

Not all individuals appear to be susceptible to a high sodium intake with about 50% of hypertensive patients being classified as sodium-sensitive.

High sodium intake and blood pressure increases in intracellular calcium, insulin resistance, paradoxical rise in atrial natriuretic peptide.

Mechanisms behind salt sensitivity a defect in renal sodium excretion and an increased rate of proximal sodium reabsorption.

Sodium Regulation

Renin-Angiotensin-Aldosterone System

The renin-angiotensin-aldosterone system is a key system involved in the modulation of blood pressure.

Sympathetic Over-activity

Over-activation of the sympathetic nervous system may also play a role in the development and maintenance of primary hypertension for some individuals.

Direct activation of the SNS may lead to enhanced sodium retention, insulin resistance, and baroreceptor dysfunction.

Regardless of which mechanism(s) underlie the role the SNS may play in the development of primary hypertension,

the SNS remains a target of many antihypertensive agents.

Peripheral Resistance

Elevated peripheral arterial resistance is a hallmark of primaryhypertension.

The increase in peripheral resistance typically observed may be due to a reduction in the arterial lumen size as a result of vascular re-modeling.

This remodeling, or change in vascular tone, may be modulated by various endothelium derived vasoactive substances, growth factors, and cytokines.

This increase in arterial stiffness results in the observed increase in systolic blood pressure.

Presentation of Primary (Essential) HypertensionGeneralAge: prevalence of hypertension is likely to be highest with middle-age or older patients.Sex: men have a higher prevalence of hypertension than women until age 55.Symptoms The primary hypertension patient may be asymptomatic or may have major

cardiovascular disease risk factors.Signs Adult patients with an average of two or more previous blood pressure readings

(systolic, SBP; diastolic, DBP) indicating either:

Laboratory Tests (Not necessarily indicative of hypertension, but may be seen in hypertensive patients)

Fasting lipid panelLow-density lipoprotein greater than 160 mg/dLTotal cholesterol greater than 240 mg/dL High-density lipoprotein less than 40 mg/dL Triglycerides greater than 200 mg/dL

Fasting blood serum or plasma glucoseImpaired fasting glucose of 100–125 mg/dLDiagnose diabetes with glucose greater than or equal to 126 mg/dL Abnormal test may indicate hypertension-related damage.

Serum creatinine elevated (greater than 1.2 mg/dL)

Microalbuminuria (protein in urine which is excreted at a rate of 30–300 mg per 24 hours or 20–200 mcg/minute)

TREATMENT

Desired Outcomes

Hypertension management by non-pharmacologic and pharmacologic therapies has proven useful in reducing the risk of heart attack, heart failure, stroke, and kidney disease morbidity and mortality.

For every 20 mm Hg systolic or 10 mm Hg diastolic increase in blood pressure, there is a doubling of mortality for both ischemic heart disease and stroke.

The goal of blood pressure management is to reduce the risk of cardiovascular disease and target organ damage.

Non-pharmacologic Treatment: Lifestyle Modifications

DASH = Dietary Approaches to Stop Hypertension.

Patient Care and Monitoring1. Measure patient blood pressure twice, at least 1 minute apart in a sitting

position, and then average the readings to determine if blood pressure is adequately controlled.

2. Conduct a medical history. Does the patient have any compelling indications? Is the patient pregnant?

3. Conduct a medication history (prescription, over-thecounter, and dietary supplements) to determine conditions or causes of hypertension. Does the patient take any medications, supplements, herbal products, or foods that may elevate SBP or DBP? Does the patient have drug allergies?

4. Review available laboratory tests to examine electrolyte balance and renal function.

Patient Care and Monitoring4. Review available laboratory tests to examine electrolyte balance

and renal function.

5. Discuss lifestyle modifications that may reduce blood pressure with the patient. Determine what nonpharmacologic approaches might be or have been helpful to the patient.

6. Evaluate the patient if pharmacologic treatment has reached the target blood pressure goal. If the patient is at the goal, skip to step 8.

7. If patient is not at goal BP, assess efficacy, safety, and compliance of the antihypertensive regimen to determine if a dose increase or additional antihypertensive agent (step 8) is needed to achieve goal blood pressure.

Patient Care and Monitoring8. Select an agent to minimize adverse drug reactions and

interactions when additional drug therapy is needed. Does the patient have prescription coverage or is the recommended agent in the formulary?

9. Open a dialogue to address patient concerns about hypertension and management of the condition.

10. Provide a plan to assess the effectiveness and safety of therapy. Follow-up in 2 to 4 weeks if the medication regimen has changed, otherwise semi-annual or annual

11. clinic visits to assess blood pressure, electrolyte balance, and renal function should occur.

HEART FAILURE

Heart failure (HF) is defined as the inadequate ability of the heart to pump enough blood to meet the blood flow and metabolic demands of the body.

Heart failure is a clinical syndrome characterized by a history of specific signs and symptoms related to congestion and hypoperfusion.

Etiology

Heart failure is the eventual outcome of numerous cardiac diseases or disorders. Heart failure can be classified by the primary underlying etiology (ischemic or nonischemic).

The most common causes of HF are CAD, hypertension, and dilated cardiomyopathy.

Coronary artery disease resulting in an acute MI and reduced ventricular function is a common presenting history.

Non-ischemic etiologies include -Hypertension // viral illness // thyroid disease // excessive alcohol use // illicit drug use // pregnancy-related heart disease // familial congenital disease // valvular disorders.

Clinical Presentation and Diagnosis of Heart Failure

GeneralPatient presentation may range from asymptomatic to cardiogenic shock.

Symptoms• Dyspnea, particularly on exertion• Orthopnea• Shortness of breath (SOB)• Paroxysmal nocturnal dyspnea• Exercise intolerance• Tachypnea• Cough• Fatigue• Nocturia and/or polyuria• Hemoptysis• Abdominal pain• Anorexia• Nausea• Bloating• Ascites• Mental status changes• Weakness• Lethargy

Laboratory Tests

• BNP greater than 100 pg/mL or N-terminal proBNP greater than 300 pg/mL

• Electrocardiogram (ECG): May be normal or could show numerous abnormalities including acute ST-T–wave changes from myocardial ischemia, atrial fibrillation, bradycardia, and LV hypertrophy.

• Serum creatinine: May be increased owing to hypoperfusion; preexisting renal dysfunction can contribute to volume overload.

• Complete blood count: Useful to determine if heart failure is due to reduced oxygen-carrying capacity.

• Chest x-ray: Useful for detection of cardiac enlargement, pulmonary edema, and pleural effusions.

• Echocardiogram: Used to assess LV size, valve function, pericardial effusion, wall motion abnormalities, and ejection fraction.

B-type (formerly brain) natriuretic peptide (BNP)

TREATMENT OF CHRONIC HEART FAILURE

Desired Therapeutic Outcomes

There is no cure for HF.

The general management goals for chronic HF include preventing the onset of clinical symptoms or reducing symptoms, preventing or reducing hospitalizations, slowing progression of the disease, improving quality of life, and prolonging survival.

Pharmacologic Treatment

DiureticsDiuretics have been the mainstay for HF symptom managementfor many years.

Diuretics are used for relief of acute symptoms of congestion and maintenance of euvolemia.

These agents interfere with sodium retention by increasing urinary sodium and free water excretion.

Loop Diuretics Used in Heart Failure

Neuro-hormonal Blocking Agents

Agents with proven benefits in improving symptoms, slowing disease progression, and improving survival in chronic HF target neurohormonal blockade.

These include ACE inhibitors, ARBs, b-adrenergic blockers, and aldosterone antagonists.

Angiotensin IIAngiotensin II is a key neurohormone in the pathophysiology of HF.

The vasoconstrictive effects of angiotensin II lead to an increase in systemic vascular resistance (SVR) and blood pressure.

The resulting increase in afterload contributes to an increase in myocardial oxygen demand. In the kidneys, angiotensin II enhances renal function acutely by raising intraglomerular pressure through constriction of the efferent arterioles.

However, the increase in glomerular filtration pressure may be offset by a reduction in renal perfusion secondary to angiotensin II’s influence over the release of other vasoactive neurohormones such as vasopressin and endothelin-1 (ET-1).

Angiotensin II also potentiates the release of aldosterone from the adrenal glands and norepinephrine from adrenergic nerve terminals.

Additionally, angiotensin II induces vascular hypertrophy and remodeling in both cardiac and renal cells.

Clinical studies show that blocking the effects of the RAAS in HF is associated with improved cardiac function and prolonged survival.

Thus, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the cornerstone of HF treatment.

Aldosterone’s contribution to HF pathophysiology is also multifaceted.

Renally, aldosterone causes sodium and water retention in an attempt to enhance intravascular volume and CO. This adaptive mechanism has deleterious consequences since excessive sodium and water retention worsen the already elevated ventricular filling pressures.

Aldosterone also contributes to electrolyte abnormalities seen in HF patients. Hypokalemia and hypomagnesemia contribute to the increased risk of arrhythmias. In addition, evidence supports the role of aldosterone as an etiologic factor for myocardial fibrosis andcardiac remodeling.

Elevated aldosterone concentrations have been associated with more severe cardiac disease and a poorer prognosis in HF. Thus, aldosterone antagonism has become an important therapeutic target for improvement of long-term prognosis.

Aldosterone

Endothelin-1, one of the most potent physiologic vasoconstrictors, is an important contributor to HF pathophysiology.

Endothelin-1 binds to two G-protein coupled receptors, endothelin-A (ET-A) and endothelin-B (ET-B). Endothelin-A receptors mediate vasoconstriction and are prevalent in vascular smooth muscle and cardiac cells. Endothelin-B receptorsare expressed on the endothelium and in vascular smooth muscle, and receptor stimulation mediates vasodilation.

Endothelin