A 76-year-old male with a medical history of diabetes and hypertension was brought to the emergency department (ED) by ambulance, with complaint of generalized weakness and mechanical fall. Patient was found on the ground on emergency medical services (EMS) arrival and was hypoxic to 89% on room air, which improved with 2 L of oxygen. As per patient, he had a positive COVID-19 test 1 week prior.
His initial symptoms were dry cough, worsening anorexia, worsening of generalized weakness, and lightheadedness for 1 week. Home medications included losartan and amlodipine. In the ED, his blood pressure (BP) was noted to be 185/95 mmHg, heart rate of 85 beats/min, afebrile, and oxygen saturation of 98% on 2 L nasal cannula. His physical examination showed bibasilar crackles on chest exam. Electrocardiogram (ECG) was unremarkable. Computed tomography (CT) of the head did not show any acute findings, and chest X-ray showed multifocal pneumonia. Laboratory tests showed an elevated inflammatory marker (see Table 8-1). He was started on ceftriaxone, azithromycin, and remdesivir. His BP was persistently elevated, and he was started on intravenous labetalol. He was transferred to the coronary care unit. Later he started to improve and was transitioned to oral antihypertensive medications. He completed antibiotics for 5 days and reported feeling better and was discharged home.
TABLE 8-1Inflammatory Markers ||Download (.pdf) TABLE 8-1 Inflammatory Markers
|Lactate dehydrogenase ||1037>>528>>564 |
|C-reactive protein ||42.56>>127.47>>62.48 |
|D-dimer ||473>>521>>420 |
|Ferritin ||1179 |
As per definition based on the American College of Cardiology and American Heart Association guidelines released in 2017, approximately 45 million adults in the United States are diagnosed with hypertension. The global burden of hypertension, which currently exceeds 1.4 billion people, is expected to exceed 1.6 billion adults by year 2025 and as of today hypertension remains the leading cause of death across the globe, especially in high-income countries.
The latest definition of hypertension uses the following BP cutoffs:
|BP Category ||SBP (mmHg) || ||DBP (mmHg) |
|Normal ||<120 ||and ||<80 |
|Elevated ||120-129 ||and ||<80 |
|Hypertension || || || |
|Stage 1 ||130-139 ||or ||80-89 |
|Stage 2 ||≥140 ||or ||≥90 |
Patients with hypertension have associated modifiable and nonmodifiable risk factors. Among the modifiable risk factors, the common factors are cigarette smoking, diabetes mellitus, hypercholesterolemia, obesity, physical inactivity, and unhealthy diet. Relatively fixed risk factors are chronic kidney disease, family history of hypertension, increased age, low-socioeconomic status, male gender, obstructive sleep apnea, and psychosocial stress.
Hypertension and COVID-19
Today, the world is seriously affected by a global pandemic caused by SARS-CoV-2, which has caused huge loss of life, a significant economic crisis, and significant healthcare access problems. Due to various lockdown implementations and reduced mobility, various risk factors associated with hypertension are on the rise. Increased weight, indiscretion with dietary habits, physical inactivity, difficulty accessing medical healthcare, and fear of going to medical facilities have caused worsening factors contributing to hypertension. Whether these factors are going to play a major part in long-term outcomes remains to be seen. Especially worth mentioning is the fear of accessing healthcare facilities during the initial part of pandemic, during which hospitals witnessed a sudden decrease in the number of myocardial infarction patients coming to the hospital and undergoing primary percutaneous coronary interventions.
Hypertension is found to be common among patients hospitalized for COVID-19. Studies have shown that the prevalence of hypertension in patients with COVID-19 stands between 25% and 30%. However, whether it affects outcomes after admission due to COVID-19–related complications is neither clear nor confirmed. Because COVID-19 is known to cause worse outcomes in the elderly patient population, and prevalence of hypertension is also known to increase with age, the relationship may not be causal; it could be just an association due to age.
A great deal of interest arose in hypertension and COVID-19 association when it was discovered that angiotensin-converting enzyme 2 (ACE2) is an entry point for SARS-CoV-2 virus particles into the human body. This interaction between the renin-angiotensin-aldosterone system (RAAS) and SARS-CoV-2 has been an area of research lately.
The RAAS system is known to exert its effect on endothelial cell dysfunction, vascular remodeling, and hypertension.
Renin is produced by juxtaglomerular cells in the kidneys and is a protease that cleaves angiotensinogen produced by this liver. This leads to the production of angiotensin I (Ang 1), which is further converted to angiotensin II by ACE. ACE enzymes are most abundant in lungs; however, they are also found in tissues and vessels. Angiotensin II (Ang 2) exerts its effects through AT1 and AT2 receptors. Activation of AT1 receptors causes elevated BP, glucose intolerance, and atherosclerosis. AT2 receptor activation usually exerts protective effects by activating nitric oxide production and endothelial-dependent vasodilatation.
Another important discovery is the production of heptapeptides Ang 1 through 7 (Ang 1-7) from both decapeptide Ang I and from Ang II. Ang 1-7 is produced from Ang I by endopeptidase and from Ang II by ACE homolog ACE2. This product, Ang 1-7, acts through the MAS pathway and exerts a multitude of protective effects in vascular biology.
A recent Prospective Urban Rural Epidemiology (PURE) study found increased levels of ACE2 associated with increased cardiovascular disease (CVD), possibly signifying increased downstream resistance to ACE2 effects, which increases the circulating levels of the enzyme.
Patients with hypertension are often asymptomatic; hence all persons older than 18 years of age should have their BP checked at least once and, if elevated, should undergo repeat measurements after an interval. Patients who are diagnosed with hypertension need careful assessment of risk factors including history of personal CVD, diabetes mellitus, dyslipidemia, chronic kidney disease, smoking status, diet, alcohol intake, physical activity, and psychosocial aspects. Family history of premature atherosclerosis, hypertension, diabetes, and hypercholesterolemia should also be evaluated. Patients with established hypertension should be assessed for target organ damage and assessed for cardiovascular risk. Patients who are young at diagnosis and have significant muscle weakness, arrythmias, flash pulmonary edema, palpitations, frequent headaches, snoring, and signs and symptoms suggestive of thyroid disease should be investigated for secondary causes of hypertension.
History and physical examination
Patients diagnosed with hypertension should undergo careful assessment for physical examination to look for signs of secondary hypertension and for target organ damage. The presence of carotid and renal bruits, enlarged kidney, enlarged thyroid gland, abdominal striae, radiofemoral delay, pedal edema, raised jugular venous pulse, and cardiac murmurs can hint at potential causes of hypertension or target organ damage.
Laboratory evaluation should include serum sodium, potassium, creatinine, lipid profile, fasting glucose; urine dipstick; and 12-lead ECGs. Based on clinical suspicion, additional laboratory investigations should be ordered including echocardiogram, carotid ultrasound, renal ultrasound, renal artery duplex, fundoscopic imaging, ankle brachial index, aldosterone-renin ratio, plasma free metanephrines, late-night salivary cortisol, urine albumin/creatinine ratio, uric acid levels, or liver function tests.
Treatment of hypertension involves a multifactorial approach with involvement of the patient, physician, and social support. Lifestyle interventions are important and a necessary part of the multidisciplinary treatment of hypertension. Smoking cessation, regular exercise, weight reduction, low sodium intake, the Dietary Approach to Stop Hypertension (DASH) diet, and stress reduction are initial and necessary interventions.
Drug treatment includes primary agents, such as oral thiazide or thiazide-type diuretics, ACE inhibitors, angiotensin receptive blockers (ARBs), and calcium channel blockers (CCBs; dihydropyridines and nondihydropyridines). Secondary agents include loop diuretics, potassium-sparing diuretics, aldosterone antagonists, beta blockers (with cardioselective, vasodilatory, noncardioselective, intrinsic sympathetic activity, and combined α- and β-receptor activities), centrally acting alpha-2 agonists (clonidine, methyldopa), and directly acting drugs including hydralazine and minoxidil.
ACE inhibitors and COVID-19
ACE inhibitors and ARBs commonly used as antihypertensives are known to increase ACE2 levels. Because the ACE2 enzyme has also been found to be the receptor protein for SARS-CoV-2, concerns arose whether use of ACE inhibitors or ARBs causing increased levels of ACE2 could worsen COVID-19 infection by providing more entry points for SARS-CoV-2. However, large studies have failed to find any harmful effects of ACE inhibitors or ARBs in patients infected with SARS-CoV-2. So far, the consensus is to continue antihypertensives without any change in treatment regimes.
Aggressive need for BP control for hospitalized patients
Patients who are seriously ill and affected by COVID-19–related complications should be continued on antihypertensives. However, the decision to aggressively control BP should be weighed with anticipation of progression of COVID-19–related complications. If concerns of serious decompensation are anticipated, then BP goals should be liberalized, as the risk of developing hypotension in the short term would outweigh the benefits of tight BP control over the long term. (1-4)
Fear of being exposed to coronavirus has led to difficulties in accessing healthcare. Although public health measures are in effect, the concern remains significant. Telehealth provides the opportunity to provide continued medical care in these unprecedent times. It reduces the risk of exposure to both patient and healthcare providers. However, once concerns are raised and serious issues are anticipated, the patient should be appropriately advised for in-person appointments or to seek urgent in hospital care.