Chapter 8: Hypertension with other conditions

Obesity, sleep apnoea, pulmonary disease, gout, inflammatory disease, glaucoma, cancer and COVID-19 can all alter blood pressure, cardiovascular risk, medication selection and the safety of rapid treatment changes. The following sections preserve the source discussion and its limitations.

Obesity

Obesity and arterial hypertension commonly occur in the same person and often coexist with type 2 diabetes. People with obesity and hypertension may need more antihypertensive drugs than people without obesity, are more likely to have resistant hypertension, and may be particularly vulnerable to the metabolic adverse effects of some drugs.

Few hypertension trials were designed specifically for people with obesity, and evidence on combining antihypertensive treatment with weight loss is also limited. The following considerations therefore draw on available trials, observational studies and prespecified subgroup analyses rather than a single definitive trial.

Antihypertensive medication in obesity

The reasonable aim is to lower blood pressure without worsening obesity or its metabolic risk. There is no evidence that the blood-pressure target should differ solely because a person has obesity, but reaching the target is often more difficult.

A retrospective analysis of ALLHAT classified participants as normal weight (BMI<25 kg/m²), overweight (BMI 25–29.9 kg/m²) or obese (BMI>30 kg/m²). After five years, approximately two thirds achieved blood-pressure control regardless of BMI, but people with obesity required more medications.

In obesity with hypertension, it may be reasonable to begin with an ACE inhibitor, ARB or calcium-channel blocker because these classes do not generally worsen insulin sensitivity or obesity. Renin–angiotensin-system inhibitors may improve glucose metabolism, although they cannot fully prevent the high risk of type 2 diabetes associated with severe obesity and insulin resistance.

Thiazide or thiazide-like diuretics, particularly at higher doses, may worsen glucose and lipid metabolism and increase the risk of type 2 diabetes. Beta-blockers can promote weight gain, adversely affect lipids and may also increase diabetes risk; the effect may be greater when beta-blockers are combined with diuretics.

These disadvantages are attenuated or absent with vasodilating beta-blockers. Potential metabolic effects should be balanced against blood-pressure efficacy. Many people with severe obesity need combination treatment, and diuretics can be particularly effective, possibly because obesity is associated with abnormal sodium handling and volume expansion. Reduced natriuretic-peptide activity may contribute to this physiology.

Hypertension in obesity may coexist with myocardial infarction or HFrEF, in which beta-blockers have compelling indications. They may also mitigate cardiovascular effects of the sympathetic nervous system, which is activated in obesity and even more so when obesity and hypertension coexist.

In an ACCOMPLISH subgroup analysis, cardiovascular-event risk did not differ in people with severe obesity treated with an ACE inhibitor combined with either a calcium-channel blocker or a diuretic. This supports the use of combinations containing a diuretic when their stronger blood-pressure effect balances possible metabolic disadvantages. Other classes, including renin inhibitors and sacubitril/valsartan, have been studied in smaller obesity trials.

Non-pharmacological weight loss

There is strong evidence that weight loss improves metabolic risk factors and can improve blood-pressure control. In people with high-normal pressure randomised to a dietary intervention, losing 2.7 kg was associated with hypertension in 8.8% compared with 19.2% in the control group.

In TOHP phase I, men and women aged 30–54 years who lost 3.9 kg had a 2.9/2.3 mmHg reduction in systolic/diastolic pressure over 18 months, with a larger reduction in those with obesity. In TOHP phase II, people who lost at least 4.5 kg by six months and maintained the loss over 30 months achieved a greater pressure reduction and a 65% lower risk of developing hypertension.

In TAIM, people with mild hypertension and overweight or obesity lost weight and lowered pressure by 4.7 kg and 8.8 mmHg, respectively, after six months of a calorie-restricted diet compared with control groups receiving antihypertensive medication, a low-sodium/high-potassium diet, usual diet or placebo. In TONE, moderate weight loss reduced the need for antihypertensive treatment by approximately 30% in older adults with hypertension taking one drug.

Weight loss may reduce sympathetic activity by reversing abnormalities in natriuretic-peptide regulation. Calorie restriction and increased physical activity are therefore recommended. A dietitian may be helpful, although maintaining long-term weight loss remains difficult even when multidisciplinary programmes are available.

Weight-loss medication

Very few currently available weight-loss drugs have been tested in people with obesity and hypertension with blood pressure as the primary outcome. Newer weight-loss drugs evaluated for cardiovascular protection in large trials of people with type 2 diabetes and overweight or obesity have not been shown to improve cardiovascular outcomes in people without diabetes who have overweight or obesity. Their role in blood-pressure management is therefore unclear.

A recent meta-analysis found that not every weight-reducing drug improves pressure control. In one study, orlistat plus a calorie-restricted diet was more effective than diet alone for blood-pressure control. Low-dose topiramate/phentermine, not approved in Europe, lowered body weight and pressure in some studies. Responses with liraglutide were modest, while a clear pressure benefit was absent with naltrexone/bupropion.

Once-weekly semaglutide, a GLP-1 receptor agonist, produced greater weight loss than daily liraglutide and was associated with a larger reduction in systolic and diastolic pressure. Seventy-two weeks of once-weekly tirzepatide, a dual GIP/GLP-1 receptor agonist, reduced weight in a dose-dependent manner: weight fell by 20.9% with the 15 mg dose compared with 3.1% with placebo, and systolic pressure was 6.2 mmHg lower than with placebo.

Metformin is associated with modest weight loss, and SGLT2 inhibitors produce a consistent, although moderate, reduction in body weight. Weight-loss drugs should not generally be prescribed primarily to treat hypertension. When prescribed for another indication, however, pressure reduction may be an additional benefit. GLP-1 and dual GIP/GLP-1 receptor agonists have become relevant options for people with BMI at least 27 kg/m² but below 30 kg/m² who have overweight and hypertension, as well as for approved indications such as diabetes or obesity.

Bariatric surgery

Bariatric procedures include sleeve gastrectomy, Roux-en-Y gastric bypass and biliopancreatic diversion, with the shared aim of reducing body weight. They differ in weight loss, adverse effects and weight-independent effects on gut hormones.

The non-randomised Swedish SOS study found that surgical weight loss improved cardiovascular morbidity and mortality in men and women with BMI of at least 34 or 38 kg/m², depending on sex. A meta-analysis including 269,818 patients who underwent bariatric surgery and 1,270,086 controls supported these findings. Metabolic and other risk factors also improve persistently after surgery, lowering overall cardiovascular risk.

Long-term reductions in sympathetic activity and increased natriuretic-peptide availability may contribute to the benefits. The long-term blood-pressure reduction is nevertheless modest relative to the large weight loss. The SOS analysis suggested that the reduction in incident hypertension was clearest during the first few years, although the larger meta-analysis found a substantial reduction in hypertension incidence after bariatric surgery.

A recent randomised trial in treated patients with hypertension and BMI 30–39.9 kg/m² found that, compared with medical treatment, the Roux-en-Y gastric-bypass group needed fewer antihypertensive drugs to maintain pressure below 140/90 mmHg for up to three years. At one year, resistant hypertension was present in 14.9% of the medical-treatment group and in none of the surgical group.

Bariatric surgery may therefore be considered for selected people with severe obesity and hypertension after a multidisciplinary assessment. It is not a substitute for individual risk assessment, long-term nutritional follow-up or ongoing blood-pressure monitoring.

Obstructive sleep apnoea

Obstructive sleep apnoea is common in obesity and is associated with hypertension through intermittent hypoxia, sympathetic activation, sleep fragmentation, abnormal intrathoracic pressure and metabolic changes. It should be suspected with loud snoring, witnessed apnoeas, excessive daytime sleepiness, morning headache, resistant hypertension or an appropriate clinical phenotype.

Continuous positive airway pressure improves nocturnal breathing and may lower blood pressure, but the average reduction is usually modest and adherence is crucial. Weight reduction, avoidance of alcohol close to bedtime and treatment of other sleep disorders may also help. Sleep-apnoea treatment complements, rather than replaces, standard blood-pressure treatment.

Asthma and COPD

Asthma and chronic obstructive pulmonary disease require attention to respiratory symptoms, bronchodilators, steroid exposure and drug interactions. A beta-blocker should not be withheld automatically when there is a strong cardiovascular indication, but cardioselectivity, dose and respiratory response should be considered. Non-selective beta-blockade may worsen bronchospasm in susceptible people. Blood-pressure treatment should be individualised with the respiratory and cardiovascular indications in view.

Gout and uric acid

Hyperuricaemia and gout commonly coexist with hypertension and chronic kidney disease. Thiazide and loop diuretics can raise uric acid and precipitate gout, although their blood-pressure and volume-control benefits may remain important. Where clinically appropriate, the medication regimen can be reviewed and alternatives considered. Lowering uric acid has not been established as a universal strategy for preventing cardiovascular or renal events in people with hypertension.

Immune-mediated inflammatory diseases

Rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus are associated with inflammation, vascular dysfunction and increased cardiovascular risk. Blood pressure should be measured carefully because treatment of inflammation, corticosteroid exposure, renal involvement and NSAID use can all affect the result.

In rheumatoid arthritis, cardiovascular risk is higher than in the general population and may improve when inflammation is controlled, but disease-modifying therapy does not remove the need for standard risk-factor treatment. In psoriatic arthritis, obesity, metabolic syndrome and inflammatory activity can cluster with hypertension. In systemic lupus, renal involvement and glucocorticoids are particularly important, and hypertension may signal active or chronic kidney disease. NSAIDs and steroids can raise pressure or worsen fluid retention and should be reviewed.

Glaucoma

Glaucoma and hypertension require coordination because ocular pressure, optic-nerve perfusion and systemic blood pressure may not move in the same direction. Excessive nocturnal blood-pressure reduction can theoretically compromise optic-nerve perfusion in susceptible patients. Blood-pressure and glaucoma treatment should therefore be coordinated rather than adjusted in isolation.

Hypertension and cancer

Hypertension may be associated with cancer through shared risk factors, age, obesity, kidney disease and treatment effects. Cancer therapies can cause new hypertension, worsen pre-existing hypertension or interact with antihypertensive medication. Patients benefit from coordination between oncology, cardiology or hypertension specialists, primary care and pharmacy.

Hypertension associated with cancer and its treatment

VEGF-pathway inhibitors, including oral tyrosine-kinase inhibitors and anti-VEGF antibodies, can produce clinically important and sometimes rapid hypertension through endothelial dysfunction, reduced nitric oxide, vascular rarefaction and renal effects. Baseline pressure should be measured accurately and monitored during treatment.

Other anticancer drugs can also affect pressure through renal injury, fluid retention, sympathetic effects, steroid exposure or drug interactions. Adjuvant treatment, radiotherapy and surgery may produce additional short-term changes. Decisions about continuing or interrupting anticancer therapy should be made with the oncology team and should not be based on a single unsustained reading.

Monitoring before and during cancer treatment

Before active cancer treatment, confirm the diagnosis of hypertension, assess cardiovascular risk and HMOD, review kidney function and electrolytes, and document current medication and adherence. Home or ambulatory measurements can distinguish sustained from white-coat hypertension and provide a baseline for treatment-related changes.

During treatment, monitor blood pressure frequently, especially after starting or increasing a VEGF inhibitor. Evaluate symptoms, urine protein, renal function and evidence of heart failure or ischaemia. Management should be a multidisciplinary, team-based process so that effective blood-pressure control does not unnecessarily delay cancer treatment.

Choice of antihypertensive drugs in active cancer

Thiazide or thiazide-like diuretics should generally be used only when needed for pressure or fluid control and with caution. They may increase calcium in people with bone malignancy, increase arrhythmia risk from hypokalaemia and QT-prolonging anticancer drugs, worsen SIADH-related hyponatraemia and aggravate volume depletion or dehydration. A dihydropyridine calcium-channel blocker with a renin–angiotensin-system blocker may therefore be preferred in many patients.

Non-dihydropyridine calcium-channel blockers, sometimes used for rate control when beta-blockers are contraindicated or not tolerated, can be problematic in selected patients with cancer. They moderately inhibit CYP3A4 or P-glycoprotein and may interact with some oral kinase inhibitors that are substrates of these pathways. Their negative inotropic effect may also worsen heart failure caused by cardiotoxic therapy. Careful use can still be considered in selected patients when relevant interactions are absent.

VEGF-inhibitor-induced hypertension

Randomised evidence to prevent or treat new hypertension caused by anticancer treatment, such as VEGF inhibition, remains limited. Sodium restriction may help: in a small experimental study of 16 patients, limiting sodium to 4 g per day with dietary counselling reduced VEGF-inhibitor-associated hypertension by approximately 50%.

In a retrospective cohort of 343 patients treated with oral VEGF inhibitors—sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib or cabozantinib—approximately half developed a major rise, defined as 20 mmHg systolic or 10 mmHg diastolic. Normal baseline pressure and pazopanib treatment were identified as important risk factors. Calcium-channel blockers and renin–angiotensin-system blockers lowered systolic pressure by 24.1 and 18.2 mmHg and diastolic pressure by 12.0 and 11.0 mmHg, respectively.

During VEGF-inhibitor treatment, any antihypertensive therapy should be monitored carefully, for example with home readings, and reduced or temporarily stopped during treatment interruptions if needed because the risk of hypotension may rise.

Survivors of cancer

Early follow-up after active cancer treatment is important. Blood pressure may change rapidly when a drug causing a reversible rise is stopped, requiring reverse titration or eventual discontinuation of previous antihypertensive therapy to prevent hypotension.

People with pre-existing hypertension may also develop progression of HMOD or new organ injury from the cardiovascular toxicity of anticancer therapy. Follow-up should therefore monitor for HMOD according to individual risk factors and treatment phenotype. Long-term home blood-pressure monitoring is generally useful because long-term cancer survivors, including childhood-cancer survivors, have increased risks of hypertension and cardiovascular events.

Severe worsening of hypertension during anticancer treatment may also indicate a previously unrecognised secondary cause. Appropriate testing should be considered when the clinical pattern suggests one.

COVID-19 and hypertension

SARS-CoV-2, the cause of COVID-19, was associated during the acute phase and the first pandemic year with substantial excess mortality, including stroke, ischaemic heart disease, arrhythmia, heart failure, thromboembolism, cardiac arrest and acute or end-stage kidney injury. All of these complications are closely linked to hypertension.

Hypertension was one of the common comorbidities in people with COVID-19 and was associated with a higher risk of severe disease, defined by hospitalisation or death. In large Italian datasets, hypertension independently predicted severe or fatal COVID-19. In treated people with hypertension, higher systolic pressure showed a dose-response relationship with severe COVID-19 even after accounting for age and cardiovascular disease.

The association was initially difficult to interpret because older age was common both among people hospitalised with severe COVID-19 and among people with hypertension. A plausible explanation is that hypertension often causes subclinical HMOD in vital organs, potentially reducing resilience to severe infection. Immune-regulatory abnormalities associated with hypertension may provide an additional explanation.

COVID-19 and renin–angiotensin-system inhibitors

Early theoretical concerns suggested that ACE inhibitors or ARBs might increase SARS-CoV-2 infection or severity because the virus uses ACE2 to enter cells and experimental treatment can upregulate ACE2 expression. This raised concern that people might stop life-saving medication and consequently suffer preventable cardiovascular events.

Large observational studies available early in the pandemic consistently found that renin–angiotensin-system blockade did not increase the risk of COVID-19 infection, severe disease or death. A much larger later meta-analysis found only limited effects in either direction and highlighted the bias inherent in observational evidence. These data supported the early recommendation of scientific societies, including the ESH, that patients taking these drugs for hypertension, heart failure, coronary disease or other indications should generally not stop them without medical advice.

Hypertension care during COVID-19 lockdowns

During the first pandemic year, diagnostic and therapeutic hypertension services were substantially reduced, especially during the first lockdown. Face-to-face consultations and office measurements declined, and adherence to medication also fell. In response, remote-care programmes involving physicians, nurses and pharmacists were developed. The expansion of virtual hypertension care was one positive development, but no change in drug classes, treatment thresholds or targets was adopted specifically for COVID-19 because evidence was insufficient.

The pandemic also changed physical activity, diet, alcohol use, smoking, psychological stress, sleep and daily rhythms, as well as air pollution and environmental noise. Some changes, such as reduced traffic-related pollution and noise, could have been beneficial, but most were probably harmful. Higher office and home pressure and more uncontrolled hypertension were reported in several studies, although not consistently in all of them.

SARS-CoV-2 vaccination and hypertension

SARS-CoV-2 vaccination reduced myocardial infarction and stroke after COVID-19. This should not be interpreted as a specific direct cardiac-protective effect of the vaccine; rather, SARS-CoV-2 infection affects multiple organs and is a systemic disease.

Randomised vaccine trials did not show a consistent signal of increased blood pressure. Pharmacovigilance databases and observational studies reported an estimated pooled rate of abnormal or elevated pressure after vaccination of only 3.2%, but without randomised data a reliable causal conclusion cannot be made. Short-term stress-related or white-coat responses may have contributed.

Long COVID and hypertension

Persistent cardiovascular symptoms several months after COVID-19 are common enough to require follow-up. Pre-existing hypertension may be a modest risk factor, and hypertension may be among the more frequent reasons for medical consultation after COVID-19. Longer follow-up and more data are needed to clarify the relationship.

Evidence mentioned

• Meta-analyses of bariatric surgery associate substantial weight loss with lower hypertension burden, but surgery is not appropriate for everyone.
• VEGF-inhibitor studies describe dose-related hypertension; randomised prevention evidence remains limited.
• Large observational studies and meta-analyses during COVID-19 did not support routine discontinuation of ACE inhibitors or ARBs.