Hypertension results from a complex interaction of genes and environmental factors. Numerous common genetic variants with small effects on blood pressure have been identified as well as some rare genetic variants with large effects on blood pressure. Also, genome-wide association studies (GWAS) have identified 35 genetic loci related to blood pressure; 12 of these genetic loci influencing blood pressure were newly found. Sentinel SNP for each new genetic loci identified has shown an association with DNA methylation at multiple nearby Cpg sites. These sentinel SNP are located within genes related to vascular smooth muscle and renal function. DNA methylation might affect in some way linking common genetic variation to multiple phenotypes even though mechanisms underlying these associations are not understood. Single variant test performed in this study for the 35 sentinel SNP (known and new) showed that genetic variants singly or in aggregate contribute to risk of clinical phenotypes related to high blood pressure.

Blood pressure rises with aging and the risk of becoming hypertensive in later life is considerable. Several environmental factors influence blood pressure. High salt intake raises the blood pressure in salt sensitive individuals; lack of exercise, obesity, and depression can play a role in individual cases. The possible role of other factors such as caffeine consumption, and vitamin D deficiency are less clear. Insulin resistance, which is common in obesity and is a component of syndrome X (or the metabolic syndrome), is also thought to contribute to hypertension. One review suggests that sugar may play an important role in hypertension and salt is just an innocent bystander.

Events in early life, such as low birth weight, maternal smoking, and lack of breastfeeding may be risk factors for adult essential hypertension, although the mechanisms linking these exposures to adult hypertension remain unclear. An increased rate of high blood urea has been found in untreated people with hypertensive in comparison with people with normal blood pressure, although it is uncertain whether the former plays a causal role or is subsidiary to poor kidney function. Average blood pressure may be higher in the winter than in the summer.

Secondary hypertension results from an identifiable cause. Kidney disease is the most common secondary cause of hypertension. Hypertension can also be caused by endocrine conditions, such as Cushing's syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conn's syndrome or hyperaldosteronism, renal artery stenosis (from atherosclerosis or fibromuscular dysplasia), hyperparathyroidism, and pheochromocytoma. Other causes of secondary hypertension include obesity, sleep apnea, pregnancy, coarctation of the aorta, excessive eating of liquorice, excessive drinking of alcohol, and certain prescription medicines, herbal remedies, and illegal drugs such as cocaine and methamphetamine. Arsenic exposure through drinking water has been shown to correlate with elevated blood pressure.

The prognosis of pulmonary arterial hypertension (WHO Group I) has an "untreated" median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonale). A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% patients were alive at 2 years. With new therapies, survival rates are increasing. For 2,635 patients enrolled in The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) from March 2006 to December 2009, 1-, 3-, 5-, and 7-year survival rates were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial PAH, survival rates were 91%, 74%, 65%, and 59%. Levels of mortality are very high in pregnant women with severe pulmonary arterial hypertension (WHO Group I). Pregnancy is sometimes described as contraindicated in these women.

Pulmonary hypertension is a pathophysiologic condition with many possible causes. Indeed, this condition frequently accompanies severe heart or lung conditions. A 1973 World Health Organization meeting was the first attempted to classify pulmonary hypertension by its cause, and a distinction was made between primary PH (resulting from a disease of the pulmonary arteries) and secondary PH (resulting secondary to other, non-vascular causes). Further, primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. In 1998, a second conference at Évian-les-Bains addressed the causes of secondary PH. Subsequent third, fourth, and fifth (2013) World Symposia on PAH have further defined the classification of PH. The classification continues to evolve based on improved understanding of the disease mechanisms.

Most recently in 2015, the WHO guidelines were updated by the European Society of Cardiology (ESC) and European Respiratory Society (ERS). These guidelines are endorsed by the International Society for Heart and Lung Transplantation, and provide the current framework for understanding and treatment of pulmonary hypertension.

Portal hypertension is hypertension (high blood pressure) in the hepatic portal system – made up of the portal vein and its branches, that drain from most of the intestines to the liver. Portal hypertension is defined as a hepatic venous pressure gradient. Cirrhosis (a form of chronic liver failure) is the most common cause of portal hypertension; other, less frequent causes are therefore grouped as non-cirrhotic portal hypertension. When it becomes severe enough to cause symptoms or complications, treatment may be given to decrease portal hypertension itself or to manage its complications.

The management of ascites needs to be gradual to avoid sudden changes in systemic volume status which can precipitate hepatic encephalopathy, renal failure and death. The management includes salt restriction, diuretics (spironolactone), paracentesis, and transjugular intrahepatic portosystemic shunt.

Thrombosis prevention is initiated with assessing the risk for its development. Some people have a higher risk of developing thrombosis and its possible development into thromboembolism. Some of these risk factors are related to inflammation. "Virchow's triad" has been suggested to describe the three factors necessary for the formation of thrombosis: stasis of blood, vessel wall injury, and altered blood coagulation. Some risk factors predispose for venous thrombosis while others increase the risk of arterial thrombosis.

The overall absolute risk of venous thrombosis per 100,000 woman years in current use of combined oral contraceptives is approximately 60, compared to 30 in non-users. The risk of thromboembolism varies with different types of birth control pills; Compared with combined oral contraceptives containing levonorgestrel (LNG), and with the same dose of estrogen and duration of use, the rate ratio of deep venous thrombosis for combined oral contraceptives with norethisterone is 0.98, with norgestimate 1.19, with desogestrel (DSG) 1.82, with gestodene 1.86, with drospirenone (DRSP) 1.64, and with cyproterone acetate 1.88. Venous thromboembolism occurs in 100–200 per 100,000 pregnant women every year.

Regarding family history, age has substantial effect modification. For individuals with two or more affected siblings, the highest incidence rates is found among those ≥70 years of age (390 per 100,000 in male and 370 per 100,000 in female individuals), whereas the highest incidence ratios compared to those without affected siblings occurred at much younger ages (ratio of 4.3 among male individuals 20 to 29 years of age and 5.5 among female individuals 10 to 19 years of age).

Evidence supports the use of heparin in people following surgery who have a high risk of thrombosis to reduce the risk of DVTs; however, the effect on PEs or overall mortality is not known. In hospitalized non-surgical patients, mortality decreased but not statistically significant. It does not appear however to decrease the rate of symptomatic DVTs. Using both heparin and compression stockings appears better than either one alone in reducing the rate of DVT.

In hospitalized people who have had a stroke and not had surgery, mechanical measures (compression stockings) resulted in skin damage and no clinical improvement. Data on the effectiveness of compression stockings among hospitalized non-surgical patients without stroke is scarce.

The American College of Physicians (ACP) gave three strong recommendations with moderate quality evidence on VTE prevention in non-surgical patients: that hospitalized patients be assessed for their risk of thromboembolism and bleeding before prophylaxis (prevention); that heparin or a related drug is used if potential benefits are thought to outweigh potential harms; and that graduated compression stockings not be used. As an ACP policy implication, the guideline stated a lack of support for any performance measures that incentivize physicians to apply universal prophylaxis without regard to the risks. Goldhaber recommends that people should be assessed at their hospital discharge for persistent high-risk of venous thrombosis, and that people who adopt a heart-healthy lifestyle might lower their risk of venous thrombosis.

In those with cancer who are still walking about yet receiving chemotherapy, LMWH decreases the risk of VTE. Due to potential concerns of bleeding its routine use is not recommended. For people who are having surgery for cancer, it is recommended that they receive anticoagulation therapy (preferably LMWH) in order to prevent a VTE. LMWH is recommended for at least 7–10 days following cancer surgery, and for one month following surgery for people who have a high risk of VTEs.

In adults who have had their lower leg casted or placed in a brace for more than a week, LMWH decreased the risk of VTEs. LMWH is recommended for adults not in hospital with an above-knee cast and a below-knee cast, and is safe for this indication.

Following the completion of warfarin in those with prior VTE, long term aspirin is beneficial.

The main causes of thrombosis are given in Virchow's triad which lists thrombophilia, endothelial cell injury, and disturbed blood flow.

Patients with hypertensive encephalopathy who are promptly treated usually recover without deficit. However, if treatment is not administered, the condition can lead to death.

Several other diseases can result in retinopathy that can be confused with hypertensive retinopathy. These include diabetic retinopathy, retinopathy due to autoimmune disease, anemia, radiation retinopathy, and central retinal vein occlusion.

Kidney failure is very common in patients suffering from congestive heart failure. It was shown that kidney failure complicates one-third of all admissions for heart failure, which is the leading cause of hospitalization in the United States among adults over 65 years old. These complications led to longer hospital stay, higher mortality, and greater chance for readmission. Another study found that 39% of patients in NYHA class 4 and 31% of patients in NYHA class 3 had severely impaired kidney function. Similarly, kidney failure can have deleterious effects on cardiovascular function. It was estimated that about 44% of deaths in patients with end-stage kidney failure (ESKF) are due to cardiovascular disease.

A major aim of treatment is to prevent, limit, or reverse target organ damage by lowering the person's high blood pressure to reduce the risk of cardiovascular disease and death. Treatment with antihypertensive medications may be required to control the high blood pressure.

Anomalous pulmonary venous connection (or anomalous pulmonary venous drainage or anomalous pulmonary venous return) is a congenital defect of the pulmonary veins.

In TAPVC without obstruction, surgical redirection can be performed within the first month of life. The operation is performed under general anesthesia. The four pulmonary veins are reconnected to the left atrium, and any associated heart defects such as atrial septal defect, ventricular septal defect, patent foramen ovale, and/or patent ductus arteriosus are surgically closed. With obstruction, surgery should be undertaken emergently. PGE1 should be given because a patent ductus arteriosus allows oxygenated blood to go from the circulation of the right heart to the systemic circulation.

Causes can include pancreatitis, cirrhosis, diverticulitis, and cholangiocarcinoma. It is also a known complication of splenectomy.

Venous stasis, or venostasis, is a condition of slow blood flow in the veins, usually of the legs. Venous stasis is a risk factor for forming blood clots in veins (venous thrombosis), as with the deep veins of the legs (deep vein thrombosis or DVT). Causes of venous stasis include long periods of immobility that can be encountered from driving, flying, bed rest/hospitalization, or having an orthopedic cast. Recommendations by clinicians to reduce venous stasis and DVT/PE often encourage increasing walking, calf exercises, and intermittent pneumatic compression when possible.

Prevention is possible with Thrombosis prophylaxis methods and practices.

The most common cause of chronic venous insufficiency is reflux of the venous valves of superficial veins. This may in turn be caused by several conditions:

- Deep vein thrombosis (DVT), that is, blood clots in the deep veins. Chronic venous insufficiency caused by DVT may be described as postthrombotic syndrome.

- Superficial vein thrombosis.

- Phlebitis

- May–Thurner syndrome. This is a rare condition in which blood clots occur in the iliofemoral vein due to compression of the blood vessels in the leg. The specific problem is compression of the left common iliac vein by the overlying right common iliac artery. Many May-Thurner compressions are overlooked when there is no blood clot. More and more of them get nowadays diagnosed and treated (by stenting) due to advanced imaging techniques.

Deep and superficial vein thrombosis may in turn be caused by thrombophilia, which is an increased propensity of forming blood clots.

Arteriovenous fistula (an abnormal connection or passageway between an artery and a vein) may cause chronic venous insufficiency even with working vein valves.

Congestion of the mucosa in other parts of the gastrointestinal tract can also be seen in portal hypertension. When the condition involves the colon, it is termed "portal hypertensive colopathy".

Dilated submucosal veins are the most prominent histologic feature of esophageal varices. The expansion of the submucosa leads to elevation of the mucosa above the surrounding tissue, which is apparent during endoscopy and is a key diagnostic feature. Evidence of recent variceal hemorrhage includes necrosis and ulceration of the mucosa. Evidence of past variceal hemorrhage includes inflammation and venous thrombosis.

Treatments include anticoagulants, shunts, bypass surgery, and transplants.

DVA can be diagnosed through the Cerebral venous sinus thrombosis with collateral drainage. DVA can also be found diagnosed with Sturge–Weber syndrome and can be found through leptomeningeal angiomatosis. Demyelinating disease has also been found to enlarge Medulla veins.

The initial aim of treatment in hypertensive crises is to rapidly lower the diastolic pressure to about 100 to 105 mmHg; this goal should be achieved within two to six hours, with the maximum initial fall in BP not exceeding 25 percent of the presenting value. This level of BP control will allow gradual healing of the necrotizing vascular lesions. More aggressive hypotensive therapy is both unnecessary and may reduce the blood pressure below the autoregulatory range, possibly leading to ischemic events (such as stroke or coronary disease).

Once the BP is controlled, the person should be switched to medication by mouth, with the diastolic pressure being gradually reduced to 85 to 90 mmHg over two to three months. The initial reduction to a diastolic pressure of approximately 100 mmHg is often associated with a modest worsening of renal function; this change, however, is typically transient as the vascular disease tends to resolve and renal perfusion improves over one to three months. Antihypertensive therapy should not be withheld in this setting unless there has been an excessive reduction in BP. A change in medication, however, is indicated if the decline in renal function is temporally related to therapy with an angiotensin (ACE) converting enzyme inhibitor or angiotensin II receptor blocker, which can interfere with renal autoregulation and produce acute renal failure in patients with bilateral renal artery stenosis. (See "Renal effects of ACE inhibitors in hypertension".)

Several parenteral antihypertensive agents are most often used in the initial treatment of malignant hypertension.

- Nitroprusside – an arteriolar and venous dilator, given as an intravenous infusion. Nitroprusside acts within seconds and has a duration of action of only two to five minutes. Thus, hypotension can be easily reversed by temporarily discontinuing the infusion, providing an advantage over the drugs listed below. However, the potential for cyanide toxicity limits the prolonged use of nitroprusside, particularly in patients with renal insufficiency.

- Nicardipine – an arteriolar dilator, given as an intravenous infusion.

- Clevidipine – a short-acting dihydropyridine calcium channel blocker. It reduces blood pressure without affecting cardiac filling pressures or causing reflex tachycardia.

- Labetalol – an alpha- and beta-adrenergic blocker, given as an intravenous bolus or infusion. Bolus followed by infusion.

- Fenoldopam – a peripheral dopamine-1 receptor agonist, given as an intravenous infusion.

- Oral agents — A slower onset of action and an inability to control the degree of BP reduction has limited the use of oral antihypertensive agents in the therapy of hypertensive crises. They may, however, be useful when there is no rapid access to the parenteral medications described above. Both sublingual nifedipine and sublingual captopril can substantially lower the BP within 10 to 30 minutes in many patients. A more rapid response is seen when liquid nifedipine is swallowed.

The major risk with oral agents is ischemic symptoms (e.g., angina pectoris, myocardial infarction, or stroke) due to an excessive and uncontrolled hypotensive response. Thus, their use should generally be avoided in the treatment of hypertensive crises if more controllable drugs are available.

Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced dyspnea, paroxysmal nocturnal dyspnea and orthopnea, exercise intolerance, fatigue, elevated jugular venous pressure, and edema.

Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.