sample of research paper about hypertension

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High Blood Pressure Research

Language switcher.

As part of its broader commitment to research on cardiovascular diseases, the NHLBI leads and supports research and programs on high blood pressure. The NHLBI has funded several studies and programs to help develop new treatments for high blood pressure, many of which focus on women’s health, lifestyle interventions, and health disparities. Current studies aim to prevent pregnancy complications and improve blood pressure among people in high-risk groups.

NHLBI research that really made a difference

• NHLBI’s Systolic Blood Pressure Intervention Trial (SPRINT) found that treating to a lower systolic blood pressure target — less than 120 mm Hg — helped lower deaths from heart attack and stroke, particularly among older people who have high blood pressure. These findings informed the latest high blood pressure guidelines published in 2017. A follow-up study called SPRINTMIND found that this lower blood pressure target also reduced mild cognitive impairment, a condition that can lead to dementia. Visit  Intensive blood pressure control may slow age-related brain damage  for more information. 
• The Dietary Approaches to Stop Hypertension (DASH) Sodium Trial showed that reducing sodium as part of a healthy eating plan substantially lowers blood pressure in persons with high blood pressure. The greatest effect was seen when sodium reduction was combined with a diet that is rich in fruits and vegetables and low in saturated fat and that was previously shown to lower blood pressure, such as with the DASH Eating Plan.
• The NHLBI Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT ) was the largest hypertension clinical trial ever conducted, involving more than 600 clinics and 42,000 participants. The study compared the success of three commonly used blood pressure-lowering medicines (a calcium channel blocker amlodipine, an ACE-inhibitor lisinopril, and an alfa-receptor blocker doxazosin) with a diuretic, chlorthalidone. The trial concluded that the diuretic worked better than the other medicines to manage high blood pressure and prevent stroke, as well as some types of heart disease, especially heart failure.

Find  funding opportunities  and  program contacts  for high blood pressure research.

Current research funded by the NHLBI

Our Division of Cardiovascular Sciences and its Vascular Biology and Hypertension Branch oversee much of the research we fund on the regulation of blood pressure.

Current research on the treatment of high blood pressure

NHLBI-supported research has contributed to blood pressure treatments that have helped people around the world. High blood pressure affects millions of U.S. adults. We continue to support work on new treatments and new approaches to tailoring the right treatment for the right patient.

• Researchers at the NHLBI-funded Levy Lab are studying the role of genetics in cardiovascular disease , using resources from the Framingham Heart Study to develop promising blood pressure medicines and treatments.
• The NHLBI funds research into the connection between inflammation and high blood pressure . Better understanding of the causes of hypertension will help researchers develop treatments to improve blood pressure management and prevent early death from cardiovascular disease.
• The NHLBI supports research that improves adherence to long-term cardiovascular medicines that help to regulate blood pressure. Researchers will use pharmacy data to identify patients who fail to refill their medicines. They will then test whether reminders using text messages or interactive chat bots can help improve medicine adherence.
• The NHLBI funds research into the connection between microbiome and high blood pressure . One recent study showed that intermittent fasting in an animal model could reduce hypertension by reshaping the gut microbiota.
• Findings from the Offspring Cohort of the Framingham Heart Study (FHS) and the Coronary Artery Risk Development in Young Adults (CARDIA) study showed a close association between hypertension and late-onset epilepsy and other brain changes, respectively, which may increase the risk of cognitive decline later in life.
• A clinical trial called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH) , showed that lifestyle modification, such as by following the DASH eating plan, could significantly reduce blood pressure even in patients with resistant hypertension.
• A clinical trial, Chlorthalidone in Chronic Kidney Disease (CLICK) showed that the diuretic chlorthalidone can improve blood pressure control in patients with advanced chronic kidney disease. 
• A recent meta-analysis showed that the use of blood brain barrier-crossing ARBs and ACE-inhibitors was linked to better cognitive benefits. Supported by R01 HL080477 and T32 HL07594.

Find more NHLBI-funded studies on the  high blood pressure treatment at NIH RePORTER. 

Find out more about how the DASH diet and exercise help fight resistant high blood pressure .

Find out more about how the DASH diet and exercise help fight resistant high blood pressure.

Current research on women’s health and high blood pressure

NHLBI-supported research has helped reveal how pregnancy complications, including high blood pressure, affect the long-term health of women and their children.

• One study links preterm pregnancy to a greater chance of high blood pressure in women.
• Another study shows that women in their first trimester of pregnancy who also have higher blood pressure, high levels of glucose, insulin, or triglycerides, or obesity were more likely to experience adverse pregnancy outcomes such as gestational hypertension or diabetes, preeclampsia, or pre-term delivery. That same study also showed these women also had a higher risk of hypertension years after delivery.
• The NHLBI Maternal Morbidity and Mortality (3M) Administrative Coordinating Center identifies and prepares community-based organizations to help improve the health of pregnant women who are at higher risk of maternal death and disease.
• The NHLBI continues to fund the nuMoM2b Heart Health Study , which helps scientists understand how cardiovascular disease starts and develops in women. The study, funded by the NHLBI and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is now looking at the links between pregnancy, sleep health, and cardiovascular health .
• NHLBI’s CHAP Maternal Follow-up Study examines the impact of treatment for preeclampsia and high blood pressure during pregnancy on a woman’s future chance for developing cardiovascular disease. The results will help identify the best ways to improve the health of women younger than 40 who have mild, long-term high blood pressure.
• Another NHLBI-supported study uncovered a link between infants who had heart surgery early in life to correct a congenital heart defect, and high blood pressure in adulthood.

Find more NHLBI-funded studies on women’s health and high blood pressure at NIH RePORTER. 

Current research on health disparities and high blood pressure

African American and Hispanic adults in the United States have a higher prevalence of high blood pressure than other racial and ethnic groups. The NHLBI supports research to understand and lower high blood pressure disparities, as part of our broader commitment to addressing health disparities and inequities .

Other studies and research areas we fund to lower the burden of health disparities are listed below.

• Our RURAL: Risk Underlying Rural Areas Longitudinal Cohort Study reaches 4,000 young and middle-aged men and women from different racial and ethnic groups living in poor rural counties in four southern states. The goal of the study is to understand what causes the high rate of heart and lung disease in these regions and how to improve and prevent it.
• An NHLBI-funded study is comparing clinic-based care with a collaborative care team/stepped care approach. The collaborative care/stepped care approach, which includes education outreach by community health workers and consultations with specialists, is designed to help lower high blood pressure and heart disease risk among minorities, poor people, and people living in rural areas.
• An NHLBI-funded study aims to improve high blood pressure in African American people in the Black Belt area of Alabama. The study includes 2,000 African American people who have uncontrolled high blood pressure. The study findings will help to eliminate barriers to blood pressure treatment faced by this group.

Find more NHLBI-funded studies on high blood pressure and health disparities at NIH RePORTER. 

An NHLBI-funded study used barbershops as a venue for helping Black men lower their blood pressure .

High blood pressure research labs at the NHLBI

The NHLBI Division of Intramural Research and its Cardiovascular Branch conduct research on diseases that affect the heart and blood vessels, including high blood pressure. Other Division of Intramural Research groups, such as the Center for Molecular Medicine and Systems Biology Center , perform research on heart and vascular diseases.

Related high blood pressure programs

• NHLBI’s recently launched Disparities Elimination through Coordinated Interventions to Prevent and Control Heart Disease Risk (DECIPHeR) program to work with local communities to study different proven interventions for hypertension. In Los Angeles, 51 adult primary care clinics will use culturally tailored strategies to improve blood pressure management in this large, diverse city.
• The Chronic Hypertension and Pregnancy (CHAP) trial is examining the safety and success of medication to treat mild high blood pressure during pregnancy.
• In 2018, the NHLBI, in collaboration with NICHD, held a workshop on Predicting, Preventing and Treating Preeclampsia . Experts developed many recommendations, including new treatment strategies, for dealing with the condition, which is caused by a sudden spike of blood pressure during the second half of pregnancy.

In 2019, the NHLBI convened the HIV-associated Comorbidities, Co-infections & Complications Workshop , which resulted in strategies to support more research into the diseases, infections, and complications related to HIV. People with HIV have a higher risk of developing high blood pressure, whether or not they actively take their HIV medicine.

Explore more NHLBI research on high blood pressure

The sections above provide you with the highlights of NHLBI-supported research on high blood pressure. You can explore the full list of NHLBI-funded studies on the NIH RePORTER .

To find more studies:

• Type your search words into the  Quick Search  box and press enter. 
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• Select the  Agencies  arrow, then the  NIH  arrow, then check  NHLBI .

If you want to sort the projects by budget size — from the biggest to the smallest — click on the  FY Total Cost by IC  column heading.

Living with Hypertension: A Qualitative Research

Affiliations.

• 1 Department of Medical-Surgical Nursing, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran.
• 2 Nursing and Midwifery Care Research Center, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran.
• PMID: 28670584
• PMCID: PMC5478742

Background: Hypertension affects many aspects of the patients' life. Factors such as attitudes, beliefs and experiences, and social and cultural conditions of patients have effective roles in hypertension treatment process. The aim of this research was to explore perspectives and experiences of patients with hypertension while living with this disease.

Methods: This is a qualitative research using content analysis approach. 27 hypertensive patients who referred to hospitals affiliated to Tehran University of Medical Sciences were selected based on purposive sampling, and semi-structured interviews were carried out. Graneheim and Lundman's approach was used for analysis of data and Lincoln and Guba's criteria were used to confirm the trustworthiness of the study's findings.

Results: Experiences of the participants were divided into three main categories as follows: (1) disease shadow; (2) dual understanding of the effect of drug therapy consisting of two sub-categories known as ''perceived benefits,'' ''negative consequences''; and (3) facing the disease that includes the two subcategories of ''Compatibility'' and ''Negligence and denial''.

Conclusion: Based on the findings, patients with hypertension had experienced many physical, psychological, social, familial and spiritual problems due to the disease and their cultural context. These patients obtained positive experiences following the compatibility with hypertension. Comprehensive planning tailored to the cultural, social context and their beliefs is necessary to solve problems in these patients.

Keywords: Qualitative research; Experience; Hypertension.

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Sample Research Paper on Hypertension

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Introduction

Hypertension, also commonly referred to as high blood pressure, is one of the most ubiquitous yet nettlesome medical problems affecting millions of people around the world. Hypertension is one of the major risk factors for coronary heart disease, hemorrhagic stroke, ischemic myocardial infarction, cerebrovascular accidents, chronic renal failure and congestive heart failure among people living in industrialized countries(Mohler & Townsend, 2006).  Blood pressure is considered to be normal if it measures 120/80 orlower. In this example,120 represent the systolic blood pressure whereas 80 represent the diastolic blood pressure. However, if either systolic or diastolic blood pressure rises above 140 and 90respectively, then there is a high likelihood of one to develop hypertension. According to the National Heart, Lung and Blood Institute (NHLBI), one in three people have hypertension (Black & Elliot, 2007).  Furthermore, demographic studies have confirmed that approximately 7.5% of the adult populations worldwide have already succumbedtohypertension (Mohler & Townsend, 2006).  According to the World Health Organization, the prevalence of elevated blood pressure in adults aged 25 and above was around 40% in the year 2008 (Whitworth & Chalmers, 2003).Research studies indicate the African continent to have the highest level of hypertension prevalence with over 46% of the population being at risk from developing high blood pressure. On the other hand, America has the lowest prevalence rates of people suffering from high blood pressure with an approximately 35% of the population suffering from hypertension. In both America and Europe, men are described to be at a higher risk of developing high blood pressure as compared to women. The World Health Report that was released by the World Health Organization in the year 2002 further revealed ischemic heart disease and cerebrovascular stroke to be the leading cause of mortality worldwide (Whitworth & Chalmers, 2003).

The disease is described as being asymptomatic while a few symptoms may showcase themselves as a result of lifestyle modifications and medications. In addition to this, most of the individuals suffering from hypertension discover their diagnosis only after they have developeda cerebrovascular stroke or myocardial infarction. Even though the disease may be treated, prolonged elevated blood pressure can lead to severe consequences such as death. Some of the leading risk factors include family history, stress, obesity, tobacco use, sedentary lifestyle and aging.High blood pressure, has also been dubbed as an ‘illness for the civilized’ due to its causative factors being poor diet, lack of physical exercise and stress (Black & Elliot, 2007). Approximately 26% of the worldwide adult population is currently suffering from high blood pressure and the number is expected to further increase during the years to come.Epidemiological studies reveal that 20% –60% of the population suffering from hypertension disease is as a result of the person having genetically inherited the disease from their birth parents (Whitworth & Chalmers, 2003).

Pathophysiology

Hypertension disease is categorized into two major forms depending on the cause of the development and progression of an elevated blood pressure. Thus, hypertension is classified as either being primary/essential hypertension orsecondary hypertension. There is no clear known cause for essential hypertension whereas there is always an obvious clear cause for a person developing the secondary form of hypertension (Black & Elliot, 2007). Some of the well-defined causes of secondary hypertension include; Diabetic Nephropathy, Rennin Producing Tumors, Hydronephrosis, Polycystic Kidneys, Hypothyroidism, Hyperthyroidism, acute Stress, Arteriosclerosis and Carcinoid (Black & Elliot, 2007). In other cases, patients may have developed hypertension disease as a result of having a raised peripheral resistance with a normal cardiac output(Black & Elliot, 2007). Peripheral resistance is said to be determined by small arterioles whose walls contain smooth muscles that contract as a result of high levels of intracellular calcium concentration, eventually resulting in high blood pressure (Whitworth & Chalmers, 2003).Eventually, severe cases of hypertension may cause gross damage to the body organs such as the heart, kidneys, retina, aorta, arteries or the central nervous system.

Current trends

Thevast majority of people suffering from hypertension are put ona certain medicationso as to maintaintheir blood pressure ata normal level. In certain cases, these patients may experience side effects that arise as a result of taking the medication. In the worst cases, the prescribed medication may be ineffective to the patient who would constantly record a high blood pressure. Depending on age, the elderly may be described certain specific drugs such as an ACE inhibitor or an angiotensin-2 receptor blocker (Black & Elliot, 2007). On the other hand, patients below the age of 55 are usually prescribed different types of medication known as calcium channel blockers. Some of the calcium channel blockers include verapamil, diltiazem, felopidine and nifepidine. The common side effects of this type of drug may be headaches, swollen ankles and constipation (Mohler & Townsend, 2006).

One of the effective ways forone tocontrol their own level of blood pressure is by adjusting to a healthier lifestyle. This may be by performing regular exercises, feeding on a nutritious diet and by avoiding taking too much salt and sugar. The affected person should also halt some of the risky behaviors such as smoking, feeding on too much fat and also drinking too much alcohol (Whitworth & Chalmers, 2003).

Cultural Sensitive Care

In order to promote an improved condition to hypertension patients, it is vital for nurses to have a full comprehension of their patients’ cultures. Knowing the patient’s culture would assist the medical providers tointegrate culture as part and parcel of an effective medical treatment for hypertension (Mohler & Townsend, 2006).  The medical practitioners should consider each patient as having unique health and disease practices and beliefs as this would help them to tailor effective treatment plans that suit and meet the needs of the patient. In United States, a vast majority of the African American citizens are known to develop high blood pressure as compared to  other ethnicities that reside in America. In fact, one out of every three African-Americans tends to develop hypertension even before they attain adulthood. In fact, the majority of African-Americans with low socioeconomic backgrounds are more often than not exposed to certain common practices and risky behaviors such as smoking, drinking of alcohol, drug abuse, feeding on high cholesterol meals and in other cases they may develop chronic illnesses such as diabetes and obesity, which all eventually contribute to the individual developing high blood pressure (Mohler & Townsend, 2006).  Thus, it is vital for the health care providers to understand the culture and beliefs of their patients so as to better assess whether the patient would adhereto a certain medication plan or lifestyle changes or not. This would be essential as the medical practitioner would be able to develop suitable treatment and medication plans for the African-American citizen suffering from hypertension.

Nursing diagnosis

            This is an example of a NANDA nursing diagnosis on hypertension.

A 45 year-old woman visits the clinic and complains of constant migraines and blurred vision. In order to check on the patient’s health status, hertemperature and blood pressure had to be measured. Her temperature was 37 º Celsius but her blood pressure was 220/110. She also had diabetes and weighed 95 kg thereby indicating that she was obese.

Nursing diagnosis 1

Decreased cardiac output was as a result of myocardial ischemia, ventricular hypertrophy and vasoconstriction (Mohler & Townsend, 2006). A reduced cardiac output may also be associated with an increased peripheral vascular resistance secondary to hypertension as evidence by BP 220/110.

Nursing diagnosis 2

Patient complaining of blurred vision, and headache. The migraine or constant headache is as a result of an increased cerebral vascular pressure.

In conclusion, hypertension is a long-term medical condition that can be managed with proper treatment and medication as prescribed by doctors. High blood pressure may also develop due to an individual’s own lifestyle. Eating of food with high cholesterol, taking too much salt and sugar and poor physical fitness are some of the factors attributedto the development of hypertension. Therefore, it is an individual’s responsibility to safeguard their own health by adopting a healthy lifestyle. This requires one to be disciplined and adhere to a healthier diet whilst also doing regular physical exercise.

Whitworth, J. A., & Chalmers, J. (2003). World health organisation-international society of hypertension (WHO/ISH) hypertension guidelines. Clinical and experimental hypertension (New York, NY: 1993) , 26 (7-8), 747-752.

Black, H. R., & Elliott, W. J. (2007). Hypertension: A companion to Braunwald’s heart disease . Philadelphia, PA: Saunders Elsevier.

Mohler, E. R., & Townsend, R. R. (2006). Advanced therapy in hypertension and vascular disease . Hamilton, Ont: B.C. Decker.

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Essays on Hypertension

Brief description of hypertension.

Hypertension, or high blood pressure, is a common but serious medical condition that can lead to heart disease, stroke, and other health problems. It affects millions of people worldwide and is often referred to as a "silent killer" due to its lack of noticeable symptoms. Managing hypertension is crucial for overall health and well-being.

Importance of Writing Essays on This Topic

Essays on hypertension are important for both academic and personal exploration. They provide an opportunity to delve into the causes, effects, and management of this prevalent health issue. Through researching and writing about hypertension, individuals can gain a deeper understanding of the condition and its impact on society.

Tips on Choosing a Good Topic

• Select a specific aspect of hypertension to focus on, such as its relationship to lifestyle choices or its impact on certain demographics.
• Consider the relevance and significance of the topic in current medical research and public health discussions.
• Choose a topic that allows for critical analysis and exploration of potential solutions or interventions for hypertension.

Essay Topics

• The Role of Genetics in Hypertension
• The Impact of Diet and Nutrition on Hypertension
• Gender Disparities in Hypertension Diagnosis and Treatment
• The Relationship Between Stress and Hypertension
• The Effectiveness of Exercise in Managing Hypertension
• Public Health Interventions for Hypertension Prevention
• Hypertension in Aging Populations
• The Link Between Hypertension and Cardiovascular Disease
• Social Determinants of Hypertension in Underserved Communities
• The Psychological Impact of Hypertension Diagnosis

Concluding Thought

Writing essays on hypertension offers a valuable opportunity to explore the complexities of this prevalent health issue and contribute to the ongoing dialogue surrounding its prevention and management. By engaging with this topic through academic writing, individuals can deepen their understanding and potentially make a positive impact on public health.

Understanding Hypertension: Causes, Effects, Management

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Preventing and Controlling Hypertension for Improved Population Health

Hypertension in children: overview of healthcare policy concern and solution, important public health challenges of hypertension and obesity, the concept of preeclampsia, investigation of the link between poverty and hypertension, relevant topics.

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Free Research Paper On Hypertension

Type of paper: Research Paper

Topic: Medicine , Stress , Alcoholism , Sports , Strategy , Blood , Pressure , Hypertension

Published: 03/31/2020

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During my Practicum Experience, I encountered a patient who will be referred to as Elaine in this description. Elaine, at the time of our examination of her, weighed nearly 200 pounds, was 5’7” in height, 35 years of age, and led a sedentary lifestyle. She reported to me and the other nurses that she was a regular smoker, having smoked two packs a day since she was in her early twenties, and also drank three times a week. She has an office job, and as such does not regularly exercise. Her blood pressure was 150 over 95, leading to mild stage 1 hypertension. While she showed few outward symptoms, she often had difficulty breathing and fatigue, symptoms often associated with hypertension. She did not often check her blood pressure, which led to her being unaware of her levels being as high as they were (Buttaro et al. 1999, p. 561). In order to treat Elaine’s hypertension, two distinct prevention strategies could be implemented. First, we would advise Elaine to undergo weight loss through diet and exercise; modest reductions in body weight are proven to help reduce the risk of hypertension (NIH 2002, p. 14). Secondly, we would advise her to limit or cut out her alcohol consumption entirely; decreased consumption of alcohol directly leads to lower blood pressure (NIH 2002, p. 16). It is hoped, with these strategies, that Elaine’s blood pressure might lower, thus preventing or successfully treating her hypertension. We would also ask her to cease smoking, as that would help even further with the treatment for her hypertension (Buttaro et al. 1999, p. 571). With the help of these prevention methods and prospective treatments, it is hoped that her hypertension would be treated.

Buttaro, T.M., Trybulski, J., Bailey, P.P., & Sandberg-Cook, J. (1999). Primary care: a collaborative practice. Mosby. U.S. Department of Health and Human Services. (2002). Primary prevention of Hypertension: Clinical and Public health advisory from the National High Blood Pressure Education Program. National Institute of Health.

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Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease

Guanghong jia.

Department of Medicine-Endocrinology (G.J., J.R.S.), University of Missouri School of Medicine, Columbia.

Dalton Cardiovascular Research Center, University of Missouri, Columbia (G.J., J.R.S.).

James R. Sowers

Department of Medical Pharmacology and Physiology (J.R.S.), University of Missouri School of Medicine, Columbia.

Epidemiological studies have documented that insulin resistance and diabetes not only constitute metabolic abnormalities but also predispose to hypertension, vascular stiffness, and associated cardiovascular disease. Meanwhile, excessive arterial stiffness and impaired vasorelaxation, in turn, contribute to worsening insulin resistance and the development of diabetes. Molecular mechanisms promoting hypertension in diabetes include inappropriate activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, mitochondria dysfunction, excessive oxidative stress, and systemic inflammation. This review highlights recent studies which have uncovered new underlying mechanisms for the increased propensity for the development of hypertension in association with diabetes. These include enhanced activation of epithelial sodium channels, alterations in extracellular vesicles and their microRNAs, abnormal gut microbiota, and increased renal sodium-glucose cotransporter activity, which collectively predispose to hypertension in association with diabetes. This review also covers socioeconomic factors and currently recommended blood pressure targets and related treatment strategies in diabetic patients with hypertension.

Individuals with metabolic disorders, including insulin resistance, diabetes, and cardiometabolic syndrome, have a high prevalence of hypertension, a powerful risk factor for cardiovascular disease (CVD), kidney disease, stroke, and microvascular complications. 1 Not only is hypertension more common in patients with diabetes but also diabetes is also more common in hypertensives than in the general population. Therefore, there is a chicken-egg relationship between hypertension and diabetes (Figure ​ (Figure1 1 ). 2 To this point, hypertension occurs in 50% to 80% of patients with type 2 diabetes, who make up over 90% of the diabetic population versus ≈30% of patients with type 1 diabetes who develop hypertension. 3 , 4 That hypertension is especially common in type 2 diabetes suggests that insulin resistance may play an important role in the pathogenesis of this hypertension. Additionally, a prospective cohort study of 12 550 adults 45 to 64 years old found that type 2 diabetes was almost 2.5 times as likely to develop in patients with hypertension as in those with normal blood pressure. 3 – 5 Data from the ARIC study (Atherosclerosis Risk in Communities), the CARDIA study (Coronary Artery Risk Development in Young Adults), and the Framingham Heart Study offspring cohort in 10 893 participants showed that hypertension is a risk factor for diabetes and often precedes the development of diabetes. 4 Our understanding of mechanisms by which insulin resistance contributes to the development of hypertension in type 2 diabetes is evolving. This review focuses on basic mechanisms and environmental factors involved in promoting hypertension in diabetes, especially type 2 diabetes. It also discusses approaches for the prevention and contemporary strategies to lessen CVD and renal disease in patients with diabetes with hypertension.

Interaction of insulin resistance, diabetes, and hypertension in metabolic syndrome. Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), mitochondria dysfunction, oxidative stress, inflammation, abnormal release of extracellular vesicles (EVs) and related microRNAs (miRNAs), as well as dysregulation of gut microbiota, GLP-1 (glucagon-like peptide) and SGLT2 (sodium-glucose cotransporter 2), are involved in insulin resistance and type 2 diabetes-induced vascular stiffness and hypertension. CV indicates cardiovascular; EnNaC, endothelial epithelial sodium channel; and NO, nitric oxide.

Epidemiology of Insulin Resistance and Diabetes-Related Hypertension

There are fundamental differences in type 1 and type 2 diabetes-related hypertension. Although type 1 diabetes with insulin deficiency tends to appear in childhood or adolescence, type 2 diabetes is characterized by insulin resistance and usually takes years to develop. About 80% of type 1 diabetic individuals present with microalbuminuria and have diabetic nephropathy that typically plays a major role in the development of their hypertension. 5 Resistant hypertension is more common in these patients than nondiabetic hypertensive individuals, 6 , 7 and this resistance is associated with a higher risk of diabetic nephropathy progression. 5

Patients with the much more common type 2 diabetes often present with coexisting hypertension and diabetes in the absence of clinical renal disease. Epidemiological studies indicate that there is a very high incidence of hypertension, including increases in resistant hypertension and associated CVD in patients with type 2 diabetes. 1 In the Framingham Heart Study, type 2 diabetes was associated with a 2- to 4-fold increased risk of hypertension, peripheral arterial disease, and myocardial infarction. 8 A recent analysis of the Framingham data further showed that the population with hypertension at the time of diabetes diagnosis had higher rates of mortality for all causes and CVD events compared with normotensive persons with diabetes. 9 These data support a strong relationship between coexistent type 2 diabetes and hypertension and associated increases in CVD.

Our understanding of the role of insulin resistance in the development of elevated blood pressures is evolving. A clinic observation in 1966 from 19 patients without diabetes with essential hypertension found that these patients had significantly higher plasma insulin concentrations than a normotensive control group. 10 Approximately 50% of patients with hypertension are insulin resistant, and this defect in insulin metabolic actions increasingly appears to contribute to development of hypertension and associated CVD. 11 The Framingham Offspring Study investigated the relationship between insulin sensitivity and the 4-year incidence of hypertension and blood pressure progression in 1933 nonhypertensive participants. This analysis showed that the association between insulin sensitivity/resistance and hypertension was attenuated but remained statistically significant after adjustment for increases in body mass index. 12 These findings suggest that obesity and insulin resistance are inextricably linked in promotion of hypertension including that in type 2 diabetes.

Gender, Race, Environmental, and Socioeconomic Factors Impacting Persons With Diabetes and Hypertension

Gender and race impact the relationship between insulin resistance and diabetes-related hypertension. 13 In nondiabetic individuals the prevalence of hypertension is higher in men as compared to women until the age of 64 years when the gap closes and prevalence in females reaches that of males. 9 Interestingly, women with impaired glucose tolerance and diabetes have a higher incidence of hypertension than men with equivalent impairment in glucose homeostasis. 14 Additionally, the prevalence of hypertension is different within various ethnic groups. 15 , 16 In Black populations, the incidence of hypertension is higher when compared with White people between the age of 45 and 75 years. 15 Recent data from the Jackson Heart Study further support that greater insulin resistance is associated with a greater risk of incident hypertension and progression of blood pressure elevation among Black participants. These findings suggest that increased insulin resistance may play an important role in the high prevalence of hypertension as well diabetes in Black populations.

Socioeconomic and environmental factors likely have a substantial impact on the development of hypertension in persons with obesity, insulin resistance, and diabetes. 16 – 18 For example, foods that are traditionally considered healthy and promoted as components of the dietary approach to stop hypertension diet 18 are often unavailable to people living in disadvantaged communities of color due to either lack of access or reasons of affordability. 19 Instead, they become consumers of cheap high salt and high caloric foods, leading to obesity, diabetes, and hypertension. 18 , 19 Furthermore, lack of safe outdoor spaces discourages exercise, and exposure to environmental air and water pollution also predispose to insulin resistance, diabetes, and hypertension. 19 These social and environmental disparities likely help explain the poorer outcomes with coronavirus disease 2019 (COVID-19) infections that are seen in minorities as well as those with both diabetes and hypertension. 19

Obesity Contributes to Insulin Resistance and Diabetes-Related Hypertension

Studies in primary care settings found that 60% to 76% of overweight or obese patients have hypertension, 20 suggesting that there is a positive relationship between high blood pressure and indices of obesity. The high incidence of overweight/obesity is closely related to overconsumption of inexpensive and palatable high fat and high refined carbohydrate diets. 21 Indeed, a positive association even exists between a progressive increase in body mass index within the normal and overweight range and the risk of hypertension and CVD. 22 Related to this, data from the Framingham Heart Study showed that excess body weight accounted for appropriate 26% of cases of hypertension in men and 28% in women. 23 In addition, obese children were at ≈3-fold higher risk for hypertension than nonobese children. 24 Increased visceral adipose tissue and abdominal subcutaneous adipose tissue are especially associated with obesity-related metabolic and vascular complications. 25 For instance, in a study of 382 diabetic individuals, higher visceral adipose tissue, independent of body mass index, was associated with a higher prevalence of dyslipidemia and increased the risk for hypertension, atherosclerosis, and CVD. 26 Mechanistically, proinflammatory adipokines, including leptin and aldosterone, released from visceral fat may promote systemic and vascular insulin resistance and inflammation, impaired relaxation and vascular stiffness and development of hypertension. 27

Excessive Arterial Stiffness Is Related to Insulin Resistance and Diabetes-Induced Hypertension

While hypertension induces vascular remodeling and can lead to arterial stiffness, insulin resistance and diabetes can also promote arterial stiffening and subsequent hypertension and CVD. An increase in the augmentation index, a measure of arterial stiffness, was independently associated with all-cause mortality and a composite end point of CVD and diabetes-related death in a prospective cohort of patients with type 1 diabetes, suggesting that arterial stiffness predicts both all-cause mortality and the composite end point of CVD and diabetes-related death in patients with type 1 diabetes. 28 Recent data also suggest that the hyperinsulinemia accompanying insulin resistance is an independent risk factor for arterial stiffening. 21 Another study investigated the relationships between arterial stiffness indexes and serum insulin and glucose tolerance measurements in a biracial population of 4701 men and women aged 45 to 64. Patients with borderline abnormal glucose intolerance or type 2 diabetes had stiffer arteries than their counterparts with normal glucose tolerance. 29 It was suggested that interactive effects of elevated glucose and insulin may have a synergistic impact on arterial stiffness and play an important role in the early pathophysiology of hypertension and CVD in patients with type 2 diabetes. 30

Mechanisms in Insulin Resistance/Diabetes-Induced Hypertension

While diabetic nephropathy is the major driving factor for hypertension in type 1 diabetes, inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), mitochondria dysfunction, oxidative stress, inflammation, abnormal release of extracellular vesicles (EVs), and related microRNAs (miRs), as well as dysregulation of gut microbiota and renal SGLT2 (sodium-glucose cotransporter 2), are emerging as underlying mechanisms in the development of insulin resistance and type 2 diabetes-induced hypertension (Figure ​ (Figure1 1 ).

Inappropriate Activation of RAAS and SNS

Activation of the systemic and tissue RAAS in states of insulin resistance, obesity, and associated hyperglycemia plays an important role in the development of hypertension. In vivo and in vitro studies have shown that insulin resistance and hyperglycemia induce systemic RAAS activation in association with increased vascular resistance and arterial pressure. 31 Inhibition of the RAAS with angiotensin-converting enzyme inhibitors, AT-1R (angiotensin type 1 receptor) blockers, and MR (mineralocorticoid receptor) antagonists reduce the incidence of hypertension in patients with diabetes. 32 , 33 Inappropriate activation of the RAAS observed in insulin resistance and diabetes is likely to impair insulin signaling which contributes to development of hypertension (Figure ​ (Figure2). 2 ). To this point, angiotensin II and aldosterone increase serine phosphorylation of insulin receptor substrate proteins, leading to decreased activity of insulin downstream signaling pathways in PI3K (phosphatidylinositide 3-kinase) and Akt (protein kinase B), which leads to reduced eNOS (endothelial nitric oxide synthase) activation by insulin and reduced nitric oxide (NO) mediated vasodilation. 1

Proposed molecular mechanism in activated renin-angiotensin-aldosterone system (RAAS) and insulin resistance-related hypertension. Akt indicates protein kinase B; AT-1R, angiotensin type 1 receptor; EnNaC, endothelial epithelial sodium channel; eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; MR, mineralocorticoid receptor; NO, nitric oxide; PI3K, phosphatidylinositide 3-kinase; and SGK-1, serum and glucocorticoid regulated kinase 1.

The hyperinsulinemia associated with metabolic insulin resistance stimulates production of the vasoconstrictor ET-1 (endothelin-1) via a mitogen-activated protein kinase-dependent signaling pathway (Figure ​ (Figure2). 2 ). This contributes to vascular insulin resistance, excessive arterial stiffening, and ultimately hypertension. 1 Recently, we found that hyperinsulinemia and aldosterone increase activity of the endothelial epithelial sodium channel which leads to arterial stiffness and hypertension. 21 Related to this, both angiotensin II and aldosterone enhance SGK-1 (serum and glucocorticoid regulated kinase 1) to induce endothelial epithelial sodium channel activation leading to reduction of endothelium eNOS activity, NO production, and the development of arterial stiffening (Figure ​ (Figure2 2 ).

Inappropriate activation of the SNS is often a feature of hypertension associated with obesity and insulin resistance. In this regard, overactivity of the SNS induced, in part, by insulin resistance and hyperinsulinemia has been documented in both animal models 34 , 35 and hypertensive individuals. 36 , 37 Moreover, the presence of hypertension appears to further elevate the SNS responses to insulin. 37 Increased sympathetic tone induces stimulation of β-adrenergic receptors which promotes insulin resistance through the activation of serine/threonine kinases which blunts insulin metabolic signaling. 38 Elevated blood pressure in response to hyperinsulinemia may also be mediated by changes in baroreflex sensitivity 39 and by central nervous system hypertension promoting effects of hyperinsulinemia. 34

Role of Mitochondria Dysfunction and Excessive Oxidative Stress

The metabolic actions of insulin are dependent on normal mitochondria function, which plays a key role in energy homeostasis by metabolizing nutrients and producing ATP and cellular energy generation. Insulin resistance and diabetes are associated with mitochondrial dysfunction, characterized by reduced energy production. 40 For instance, defects in mitochondria biogenesis and dynamics in endothelial cells have detrimental consequences on their bioenergetic supply and these abnormalities contribute to endothelial dysfunction and hypertension. 40

Mitochondrial are also a major source of intracellular reactive oxygen species (ROS), and increased ROS are involved in the pathogenesis of insulin resistance, diabetes, and hypertension. 40 Related to this, almost all vascular cells, including endothelial cells, vascular smooth muscle cells, and adventitial cells, possess the ability to generate ROS. In diabetes excessive ROS production can induce damage to DNA, proteins, and lipids, leading to mitochondrial dysfunction. NADPH oxidases are also an important source of excess ROS production in the vasculature in insulin resistance and hypertension. 41 Insulin resistance and diabetes are associated with increased activation of vascular NADPH oxidases thereby inducing excessive ROS production which causes an imbalance between endothelium-derived relaxing factors and endothelium-derived contractile factors leading to associated increases in vascular tone. Excessive ROS reduce NO production and increase destruction of NO leading to diminished bioavailable NO, which contributes to arterial stiffness and hypertension. Therefore, mitochondrial dysfunction and oxidative stress are likely important instigators of hypertension in states of insulin resistance and diabetes.

Inflammation

Systemic and cardiovascular inflammation are important contributors to the development of insulin resistance, diabetes, and hypertension. For instance, enhanced TLR (Toll-like receptor)-mediated proinflammatory signaling induces activation of nuclear factor kappa B and c-Jun N-terminal kinase that promote release of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, vascular cell adhesion molecular 1, and monocyte chemoattractant protein-1. 1 These proinflammatory cytokines can impair insulin metabolic signaling and reduce insulin-mediated NO production, leading to arterial stiffness and hypertension. Furthermore, systemic and tissue inflammation are strongly related to visceral obesity. Typically, adipose tissue is composed of a variety of immune cells, such as macrophages, dendritic cells, B cells, T lymphocytes, mast cells, and neutrophils. 42 To this point, macrophages are an important driver of adipose tissue inflammation and associated metabolic disorders and hypertension.

Perivascular adipose tissue, a special local deposit of adipose tissue surrounding blood vessels, provides mechanical protection and modulates blood vessel tone. 42 In the setting of obesity, insulin resistance, and type 2 diabetes, increased NADPH oxidase-derived ROS and proinflammatory adipokines from perivascular adipose tissue contribute to vascular insulin resistance and impaired relaxation. 42 Data from the Framingham Offspring and Third Generation cohorts support the notion that altered perivascular adipose tissue volume is linked with higher thoracic and abdominal aortic dimensions and increased stiffness even after adjusting for sex, age, and CVD risk factors, including body mass index and visceral adipose tissue volume. 43

Abnormal Release of EVs and Their miRs Contribute to Insulin Resistance, Diabetes, and Hypertension

There is emerging evidence that diabetes and hypertension are associated with abnormal release of EVs, which normally mediate cell-to-cell communications. 44 For instance, the patients with hypertension often have increased circulating endothelial and platelet EVs, 45 , 46 as well as urinary endothelial microparticles. 47 Moreover, the intraperitoneal of plasma exosomes from spontaneously hypertensive rats induced an increases of systolic blood pressure in normotensive Wistar-Kyoto rats, 48 suggesting that abnormal circulating and urinary EVs may be biomarkers associated with the pathogenesis and progression of hypertension. Importantly, EVs contain various molecular constituents, including proteins, mRNA, and miR, which can be transferred from one cell to another via membrane vesicle trafficking, thereby playing a role in the pathogenesis of hypertension and related CVD. 46 To this point, the 3 subtypes of EVs are exosomes, microvesicles, and apoptotic bodies according to their different cellular origins. Recent data suggest that exosomal miRs are involved in activation of the RAAS, oxidative stress, and inflammation, and these abnormalities may induce vascular dysfunction and hypertension. 49 , 50 Indeed, increased levels of miR-223, miR-320, miR-501, miR504, and miR1 and decreased levels of miR-16, miR-133, miR-492, and miR-373 have been related to insulin resistance and diabetes-related hypertension. 51 These data suggest that exosomal miRs are important biomarkers in patients with insulin resistance, diabetes, and hypertension.

Gut Microbiota

Emerging evidence indicates that gut microbiota changes contribute to insulin resistance, diabetes, hypertension, and CVD. In this regard, the gut flora has about 100 trillion micro-organism species, and these bacteria modulate normal metabolic activities and physiological functions. For instance, the cecal bacteria from the phylum Bacteroidetes that are regarded as good bacteria are reduced in obesity, and this reduction is accompanied by a proportional increase in bad bacteria with the phylum Firmicutes . 52 These deleterious changes in gut bacteria have also been observed in insulin resistant ob/ob 53 and db/db 54 type 2 diabetic mice. A recent study provides evidence that gut microbiota may have a causal role in insulin resistance and type 2 diabetes. 55 In that study, mice receiving a transplant from an obese twin donor developed increased adiposity compared with those receiving transplants from lean twin donors. Moreover, cohousing mice harboring an obese twin’s microbiota with mice containing the lean co-twin’s microbiota prevented the development of increased body mass and obesity-associated metabolic phenotypes in obese cage mates. 55 Furthermore, oral administration of good bacteria improves the gut barrier dysfunction and metabolic disorders in obese and type 2 diabetic mice, 56 suggesting that transmissibility of intestinal microbes and the metabolic phenotype are closely linked and that it is possible to impact obesity, insulin resistance, and associated hypertension by modulating the composition of the microbiota. To this point, one study showed that gut microbiota can produce norepinephrine, thereby promoting vascular constriction and hypertension in the insulin resistant state. 57 Moreover, Enterococcus faecalis directly contributes to hypertension and renal injury by interfering lipid metabolism. 58 Thus, alterations of gut microbiota provide a new mechanism in exploring insulin resistance and diabetes-induced hypertension.

Contribution of SGLT2 to Insulin Resistance, Diabetes, and Hypertension

Glucose homeostasis is impaired in individuals with insulin resistant associated diabetes, in part, as a consequence of an increased capacity to absorb renal glucose and via proximal tubule SGLT2, which is responsible for proximal tubule reabsorption of about 90% of filtered glucose. 59 The glucose reabsorption in the kidney normally has a maximal threshold corresponding to glucose plasma levels. However, individuals with insulin resistance and type 2 diabetes have a higher threshold due to the upregulation of SGLT2 that increases proximal tubule glucose and sodium absorption, thereby contributing to hypertension and related CVD. 59 Recent large, randomized, placebo-controlled clinical trials have shown that treatment with SGLT2 inhibitors significantly reduces hypertension and CVD events and prevent the progression of renal dysfunction in individuals with diabetes. 60

Recent Therapy in Patients With Diabetes and Hypertension

The ADA 2020 Clinical Practice Guidelines suggest that nonpharmacological measures, such as weight loss, regular physical activity, and limitation of fat and total energy intake, should always be part of any blood pressure-lowering treatment as it is the cornerstone of preventive therapy in patients with diabetes with hypertension. 61 RAAS blocker may slow progression to kidney failure and CVD, and thus angiotensin II–converting enzyme inhibitors and angiotensin II receptor blockers are appropriate for initial therapy for managing hypertension in patients with diabetes. Many patients with diabetes with hypertension manifest a resistant form of hypertension requiring the addition of MR antagonists to their combination therapy. 62 , 63 This includes nonsteroidal MR antagonists (ie, Fineronone) which has recently been shown to reduce CVD events as well as reducing advancement of renal disease in patients with diabetes and kidney disease. 64 , 65

In recent years, newer antihyperglycemic medications, such as GLP-1 (glucagon-like peptide 1) agonists and SGLT2 inhibitors, have been found to lower blood pressure as well improving glucose metabolism. For instance, exenatide, an analog of GLP-1, was evaluated in the EXSCEL trial (Exenatide Study of Cardiovascular Event Lowering) clinical trial in patients with diabetes for 5 years, and exenatide reduced systolic blood pressure and low-density lipoprotein cholesterol. 66 Consistent with these data, Semaglutide, injected once-weekly at 2 doses (0.5 or 1.0 mg) for 104 weeks in the SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes), reduced blood pressure, nonfatal myocardial infarction, and stroke in patients with type 2 diabetes at high CVD risk. 67

SGLT2 inhibition induces glycosuria and promotes natriuresis resulting in reductions in blood pressure. The EMPA-REG OUTCOME study (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) showed that empagliflozin reduced blood pressure and major adverse CVD events, death, and hospitalization for heart failure. 68 In the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) in patients with type 2 diabetes and CVD, dapagliflozin treatment reduced blood pressure but failed to reduce major adverse CVD events. 69 Recent evidence from the CREDENCE trial (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) further found that canagliflozin reduced blood pressure and slowed diabetic nephropathy progression. 60 Therefore, both incretin-based and SGLT2 inhibitor therapy are beneficial in patients with diabetes with hypertension.

Summary and Future Perspectives

Insulin resistance and diabetes increase the prevalence of hypertension. The underlying molecular and cellular mechanisms include inappropriate activation of the RAAS and SNS, enhanced renal and endothelial sodium channel activation, mitochondria dysfunction, oxidative stress, inflammation, abnormal exosomal miRs, abnormal gut microbiota, as well as increased renal SGLT2 activity. Treatment strategies in patients with hypertension with diabetes include lifestyle interventions and the use of with pharmacological therapy, including RAAS blockade. Meanwhile, these patients may also benefit from treatment with GLP-1 agonists and SGLT2 inhibitors. However, there is a need for randomized and multiple-center clinical trials to better define the role of these medications in patients with diabetes with hypertension. Further research should be directed improving our understanding the pathophysiological role of insulin resistance, diabetes, and related metabolic abnormalities in the pathogenesis of hypertension.

Sources of Funding

G. Jia received relevant funding from the National Institute of Diabetes and Digestive and Kidney Diseases (DK124329) and an American Diabetes Association Innovative Basic Science Award (1-17-IBS-201). J.R. Sowers received relevant funding from the National Institutes of Health (R01 HL73101-01A and R01 HL107910-01).

Disclosures

Nonstandard abbreviations and acronyms.

For Sources of Funding and Disclosures, see page 1203.