CASE 47-1
A 58-year-old woman is hospitalized for a flare-up of progressive relapsing multiple sclerosis (MS) with motor symptoms. Her past medical history includes arterial hypertension, prediabetes, osteoporosis, and a previous gastric ulcer treated medically. She never smoked, and does not drink alcohol or take illicit drugs. Her father had a nonfatal myocardial infarction at 52 years, and her mother is alive and in good health. Her current medications include amlodipine, risedronate, omeprazole, and calcium and vitamin D supplements. Upon physical examination, she appears in good health. Her vital signs are normal, including her blood pressure at 110/82 mmHg in the right arm and 112/82 mmHg in the left arm. Cardiopulmonary auscultation and abdominal examination are unremarkable. Upon palpation, her apical impulse lasts one third of the systole and is not displaced. She has no peripheral edema, eyelids xanthelasmas, or tendinous xanthomas.
Even though age-standardized death rates attributable to cardiovascular diseases are decreasing in the United States,1 ischemic heart diseases and strokes represent the first and second causes of mortality worldwide, respectively, accounting for 25% of deaths when taken together.2 The combination of active smoking, abdominal obesity, diabetes, arterial hypertension, psychosocial stressors, irregular consumption of fruits and vegetables, sedentary lifestyle, absence of alcohol intake, and raised ApoB/ApoA1 ratio accounts for 90.4% of the population attributable risk of myocardial infarction,3 suggesting that most of the cases could be prevented through control of modifiable risk factors in primary and secondary prevention. The American Heart Association identified 7 components of ideal cardiovascular health to reduce the rates of cardiovascular diseases and stroke: smoking status, body mass index, physical activity, diet, cholesterol, blood pressure, and fasting plasma glucose.4 Data from 2007 to 2009 indicate that in all age groups, 0% of the people in the United States had an ideal profile for all 7 components,1 showing that many education efforts are still necessary to improve the cardiovascular health of the population.
What is the importance of dyslipidemia in cardiovascular diseases, including cerebrovascular diseases?
High blood cholesterol levels are strongly and independently associated with the incidence of cardiovascular diseases and mortality.5,6 Low-density lipoprotein cholesterol (LDL-C) levels are positively correlated with the aortic atherosclerosis plaque thickness in patients with idiopathic ischemic stroke,7 which might put patients with high levels at higher risks of recurrent ischemic cerebral event.8,9Dyslipidemia is thus an important target for prevention of cardiovascular diseases, including stroke. In the Unites States, dyslipidemia reached an epidemic level, with only 47.3% of the adults meeting the criteria for normal untreated total cholesterol, and 5.6% of adults with undiagnosed hypercholesterolemia.1 Nearly half of the American population ≥ 20 years old with high LDL-C levels is currently treated for high LDL-C levels.10
Management of dyslipidemia should be tailored according to a risk-based approach. The American Heart Association (AHA) and the American College of Cardiology (ACC) recommend to adapt the intensity of therapy, the indication for treatment, and the treatment targets, according to multiple factors, including age, medical history, and cholesterol levels.11 The mainstay of dyslipidemia treatment revolves around healthy lifestyle habits and pharmacologic therapy using a statin.11 Despite definitive evidence for improvements in the lipid profile with other lipid-lowering drug classes, including ezetimibe, nicotinic acid, acid bile sequestrants, and fibrates, none has demonstrated improved clinical outcomes compared to placebo in randomized trials, unlike statins.12–15 All patients with dyslipidemia should have counseling on lifestyle modifications, including a healthy diet, regular physical exercise, weight control, and tobacco cessation. Screening for diabetes and hypertension should also be performed in all patients with dyslipidemia, as well as a clinical assessment for cardiovascular diseases, including screening for cardiac and peripheral ischemic symptoms.
Unless contraindicated, and if tolerated, a high-intensity statin therapy should be administered in patients ≤75 years old in secondary prevention of atherosclerotic vascular disease, including cerebrovascular disease, coronary artery disease, and peripheral vascular disease.11 A moderate-intensity statin therapy should be used in secondary prevention for patients >75 years old. In primary prevention, patients with LDL-C levels ≥190 mg/dL should be prescribed a high-intensity statin therapy with the objective of lowering baseline LDL-C by ≥50%. The adjunctive use of a complementary lipid-lowering agent can be considered if statin therapy at the highest tolerated dose is insufficient to achieve the treatment goals. Drug interactions should, however, be monitored closely, given the increased risks of statin-induced myopathies when used concomitantly with another lipid-lowering agent, especially fibrates. In primary prevention, diabetic patients between 40 and 75 years old without known cardiovascular disease should have moderate-intensity statin therapy (or high-intensity statin therapy if estimated 10-year atherosclerotic cardiovascular disease risk is ≥7.5%, according to the Pooled Cohort Risk Assessment Equations, available at: http://my.americanheart.org/cvriskcalculator and http://www.cardiosource.org/science-and-quality/practice-guidelines-and-quality-standards/2013-prevention-guideline-tools.aspx). For primary prevention in nondiabetic patients, the 10-year risk of atherosclerotic cardiovascular disease risk should be calculated in individuals with LDL-C 90-189 mg/dL. A moderate- to high-intensity statin therapy should be initiated in patients with a ≥7.5% risk, whereas no treatment is recommended for patients with a <5% risk. A discussion regarding the risks and benefits of a moderate-intensity statin therapy should be performed with patients with a 10-year risk of 5% to <7.5% and LDL-C levels 90–189 mg/dL.
Response to treatment is assessed with a fasting lipid profile 4–12 weeks following the initiation of the statin therapy, and the dose is adjusted accordingly. Downgrading the statin dose should be considered if a patient features characteristics predisposing to statin adverse effects, including known neuromuscular disease or drug interactions. Baseline measurement of hepatic transaminases level has to be performed before initiating statin therapy, and repeated if symptoms of hepatic toxicity develop. Creatinine kinase (CK) should also be measured if myopathy symptoms develop, but a baseline measurement is not mandatory, unless neuromuscular symptoms are reported upon anamnesis.
High-density lipoprotein cholesterol (HDL-C) is inversely correlated with incident coronary artery disease.16 Fibrates, cholesteryl ester transfer protein inhibitors, and niacin all have the property of increasing the levels of HDL-C, but none have so far been shown to improve mortality and other cardiovascular endpoints,17,18 even though niacin has been shown to induce a significant regression of carotid intima-media thickness.19 Before the statin era, niacin use was associated with lower risks of stroke and of myocardial infarctions,17 but more data should be available before its use becomes widely recommended in the limited niche of statin-naïve patients. No treatment targets are thus currently recommended for levels of HDL-C.
What is the importance of arterial hypertension in cardiovascular diseases, including cerebrovascular diseases?
High blood pressure is strongly and independently associated with increased risks of strokes and myocardial infarctions.3,20 A history of hypertension independently nearly doubles the risk of acute myocardial infarction,3 and increases all-cause mortality rates.21 Hypertensive heart disease is the tenth cause of deaths worldwide, accounting for 2% of overall mortality.2 It is estimated that 77% of patients with a first stroke suffer from hypertension.1 Mimicking dyslipidemia, arterial hypertension has also reached an epidemic level, affecting up to one third of the adult population in the United States, and it is estimated that about 6% of the adults have undiagnosed hypertension.1 A significant proportion of hypertensive patients bear resistant hypertension (uncontrolled hypertension with at least 3 different drug classes).22 It is estimated that if the mean population blood pressure decreased by only 2 mmHg, the absolute prevalence of adults with ideal blood pressure would increase from 44.26% to 56.13%.1
Blood pressure should be measured with an adequately sized cuff in a calm environment, with the patient seated on a chair for at least 5 minutes, feet on the ground.23 The auscultatory method should be used. The patient should not have performed exercise, have smoked, or have drunk coffee in the 30 minutes preceding the blood pressure measurement. At least two measurements should be performed and averaged, with the arm supported at the level of the heart.23 The sphygmomanometer used should be frequently calibrated. A diagnosis of hypertension is made when the systolic blood pressure is ≥140 mmHg, or diastolic blood pressure is ≥90 mmHg. Systolic blood pressures 120–139 mmHg and diastolic blood pressures 80–89 mmHg are considered in the prehypertension range.23 If masked hypertension or the white coat syndrome is suspected, ambulatory blood pressure or home measurements can be performed.
The objectives of the initial clinical evaluation of a patient with suspected arterial hypertension are multiple: to diagnose hypertension, to screen for the presence of end-organ damage, to assess for the presence of comorbid cardiovascular risk factors, and to evaluate for the presence of a secondary cause of hypertension. Questionnaire should include a careful review of the cardiovascular antecedents, including risk factors such as diabetes, dyslipidemia, smoking history, known cardiovascular disease, alcohol consumption, and familial history. The current pharmacological profile should be reviewed for possible contribution of drugs to the elevated blood pressure. History should focus on cardiac and peripheral ischemic symptoms, symptoms of heart failure, and symptoms of diseases associated with secondary causes of hypertension, including reno-vascular and endocrinologic etiologies (mainly hyperaldosteronism, pheochromocytoma, hyperthyroidism or hypothyroidism, hyperparathyroidism, and Cushing syndrome), obstructive sleep apnea, coarctation of the aorta, and medication-related.
What are the essential components of the physical evaluation of a patient with confirmed hypertension?
Upon diagnosis of hypertension, initial physical examination requires a fundoscopic examination in search of signs of hypertensive ophthalmic damages, including microaneurysms, arteriovenous notching, papilledema, exudates, and hemorrhages. Cardiac examination should focus on the search of signs of hypertensive cardiac hypertrophy, or left ventricular failure, including prolonged apical impulse, S3 and/or S4, basal pulmonary rales, elevated jugular venous pressure, etc. Auscultation of peripheral arteries, including carotid, renal, abdominal aortic, femoral, and popliteal arteries, should be performed to assess the presence of associated peripheral vascular disease, or the possibility of renovascular hypertension. Careful lower limbs examination should focus on signs of peripheral arterial disease, which could manifest with nonhealing ulcers, or pale and cold skin with diminished pilosity.
Physical examination should be complemented with urinalysis, electrocardiography, lipid profile, and fasting plasma glucose. Moreover, baseline plasma creatinine, sodium, and potassium should be measured to assess for a secondary kidney disease, to evaluate for the potential presence of hypokalemia (suggesting hyperaldosteronism), and in prevision of the prescription of antihypertensive agents with the potential of disturbing the electrolytic balance. Radiologic or biochemical screening of a specific secondary cause of hypertension should be performed only if clinically suspected upon anamnesis and physical examination.
Lifestyle modification interventions, including maintenance of a healthy body mass index (18.5–24.9 kg/m2), and regular aerobic physical activity (3–4 sessions of moderate-to-vigorous exercise weekly, with an average of 40 minutes per session) should be emphasized in every patient diagnosed with hypertension to improve blood pressure control and to decrease the cardiovascular risk profile.24 Moreover, counseling on nutritional modifications, involving the Dietary Approaches to Stop Hypertension (DASH) eating plan (including high proportions of fruits, vegetables, low-fat dairy products, soluble fibers, whole grains and proteins from plant sources, and low saturated and trans fat) must be emphasized, with regular assessment of compliance.24 Alcohol consumption should be limited to a maximum of one drink daily for women, and 2 drinks daily for men. Estimated sodium consumption is significantly associated with increased systolic and diastolic blood pressures,25 and maximal daily consumption of 1500 to 2400 mg of sodium should be encouraged.24,26
Similarly to dyslipidemia management, treatment of hypertension should be adjusted according to the patient-specific cardiovascular risk profile, and a balance between potential benefits and harms of antihypertensive therapy, including risks of symptomatic hypotension and of drug interactions, should be carefully weighed. Diagnosis and management of hypertensive emergencies is covered in Chapter 19. In the general adult population, it is recommended to target a systolic blood pressure <140 mmHg, and a diastolic blood pressure <90 mmHg, except for patients aged 60 years or older, for whom targets of <150/90 mmHg are recommended.26 Two exceptions to this age-related difference in target blood pressure levels include adult patients with diabetes or chronic kidney disease (glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria greater than 30 g albumin per gram of creatinine in the urine), for whom a blood pressure <140/90 mmHg should be achieved at every age if treatment is tolerated.
The pharmacologic agents of choice vary according to the target population to be treated. The initial pharmacologic agent prescribed should be either a thiazide-type diuretic or a calcium channel blocker in black patients.26 In nonblack patients, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers can also be used as first-line therapy,26 but these two classes should never be used concomitantly because of the increased risk of drug-related adverse events, including renal failure.27 Hypertensive patients with concomitant chronic renal disease will benefit more of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of renal disease progression.26
Following initiation of a pharmacologic treatment for hypertension, a monthly assessment of blood pressure should be performed to adjust the dose or to add a second or a third anti-hypertensive drug to reach the treatment targets.26 Screening for medication adverse effects and symptoms of hypotension should also be performed, with measurement of blood pressure in the standing position to assess for orthostatic hypotension, defined as a decrement of 20 mmHg of the systolic blood pressure or 10 mmHg of the diastolic blood pressure after two to five minutes in the standing position following blood pressure measurement in the supine position.28 If the blood pressure targets are not reached with at least 3 antihypertensive drugs of different classes at the highest tolerated doses in compliant patients, referral to a hypertension specialist is advised, in order to eliminate secondary causes of hypertension. Alternative drug classes that can be used if initial treatment of essential hypertension is insufficient include β-blockers, aldosterone receptor blocker and other potassium-sparing diuretics, central α-agonists, direct vasodilators (including hydralazine), nitrates, peripheral α-blockers, and methyldopa.
Diabetes mellitus is also significantly associated with cardiovascular diseases, including stroke.1 Among patients >65 years old with diabetes, 16% die of a stroke.29 It is strongly and independently associated with mortality from any cause, and is directly responsible for 3% of deaths worldwide.2,30 More than 40% of adults in the United States have diabetes or an hyperglycemic condition, with higher prevalence in elderly people, and the prevalence is still increasing.31
According to the American Diabetes Association (ADA), beginning at 45 years old, everybody should be screened for the presence of diabetes or prediabetes (encompassing impaired fasting glucose and impaired glucose tolerance) at least every 3 years, or at yearly intervals in adults diagnosed with prediabetes.32 Overweight patients with additional cardiovascular risk factors or risk factors for developing diabetes, such as hypertension, dyslipidemia, sedentary lifestyle, presence of polycystic ovary syndrome, first-degree family history, previous gestational diabetes or pre-diabetes, or history of cardiovascular disease, should be screened before age 45. In addition, overweight African Americans, Latinos, Native Americans, Asian Americans, and Pacific Islanders should be screened before age 45, given their high-risk genetic background. Finally, every patient presenting classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss) or ketoacidosis should be screened for diabetes with a random plasma glucose measurement.
Screening modalities available include glycated hemoglobin (HbA1c), fasting plasma glucose, and 2-hour oral glucose tolerance tests, but the first two tests are more convenient to perform, especially in hospitalized patients. Upon a positive screening test, diagnosis of diabetes must be confirmed by a repeated confirmatory test.32 Diagnostic thresholds are shown in Table 47-1.
| Criteria | Diagnostic Thresholds | |
|---|---|---|
| Prediabetes | Diabetes | |
| Fasting plasma glucose |
| ≥126 mg/dL (7.0 mmol/L) |
| Plasma glucose after a 2-hour 75 g oral glucose tolerance test |
| ≥200 mg/dL (11.1 mmol/L) |
| Glycated hemoglobin (HbA1c) |
| ≥6.5% |
| Random plasma glucose | ≥200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia or hyperglycemic crisis | |
Promotion of healthy lifestyle habits should be emphasized in every patient diagnosed with diabetes or prediabetes, including smoking cessation, weight control, healthy nutritional habits, and regular aerobic physical exercise.32 The combination of high-intensity interval training with Mediterranean diet is effective for the control of glycemic parameters in obese patients without known coronary artery disease.33 Concomitant cardiovascular risk factors, including hypertension and dyslipidemia, should also be screened for and treated accordingly. As outlined earlier, targets for treatment of hypertension and dyslipidemia are stricter in patients with diabetes in primary prevention of cardiovascular events compared to nondiabetic patients.
Treatment of diabetes is aimed at decreasing the risks of microvascular and macrovascular complications.34 A target of HbA1c <7% should be achieved in most adults, while a stricter target of 6.5% can be considered in patients with diabetes of recent onset at low risks of adverse drug effects, particularly hypoglycemia.32 Pharmacologic treatment of diabetes encompasses many options, including biguanides, insulin secretagogues, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, inhibitors of α-glucosidase, thiazolidinediones, and parenteral insulin. Detailed description of these drug classes and of the pharmacologic treatment modalities is beyond the scope of this book. Addition of aspirin can be considered in most patients with concomitant cardiovascular disease, and in patients at high risk of developing a cardiovascular disease.32 Annual screening for microalbuminuria and for kidney dysfunction should be performed. Retinopathy screening should be performed by an ophthalmologist every 2 years, or more frequently if retinopathy is present.32 Screening for peripheral symmetric neuropathy should also be performed at least annually.32
Cigarette smoking is a major cause of cardiovascular diseases in general, and of stroke, acute myocardial infarction, and death in particular.3,35,36 It is significantly associated with an increased incidence of diabetes.37 Tobacco products, including cigarettes, cigars, and pipes, are all associated with increased mortality.35,38,39 Even a minimal consumption of 1–4 cigarettes daily nearly triples the risk of cardiovascular death, and increases independently all-cause death risk.40 Second-hand cigarette smoke exposition is also deleterious for the cardiovascular health and increases the risk of stroke in a dose-response manner.41
Smoking cessation contributes importantly to mortality reduction in secondary prevention of coronary heart disease,42 and should be encouraged in every patient. Even though former smokers have increased mortality compared to patients who never smoked regularly, benefits of smoking cessation on mortality exist in all age groups.43 The risk of stroke reaches the level of never smokers 2–4 years following smoking cessation in women.44 It should thus be encouraged in every patient.
CASE 47-2
A 68 year-old woman is scheduled for a surgical resection of a symptomatic meningioma. Her medical history is remarkable for hyperlipidemia, a previous acute myocardial infarction 8 months ago for which a drug-eluting stent was implanted, mild mitral regurgitation, paroxysmal atrial fibrillation, and an unprovoked deep vein thrombosis 10 years ago. A transthoracic echocardiographic examination performed 2 months ago disclosed normal ventricular functions and dimensions, and stable mild mitral valve regurgitation. Her current medication includes atorvastatin, aspirin, ticagrelor, ramipril, atenolol, and rivaroxaban.
What are the cornerstones of the preoperative cardiovascular evaluation of patients undergoing a noncardiac surgery?
The ACC and the AHA issued guidelines for the management of patients undergoing noncardiac surgery.45 Before planning a noncardiac surgery, 3 essential questions should be answered:
Is the surgery emergent/urgent, or elective?
Does the patient have an acute coronary syndrome?
What is the operative risk of major adverse cardiovascular events for this specific patient?
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