The exposome directly influences our genes, resulting in changes in gene function or expression that lead to the disordered biological state of diabesity. This is an important idea. The collective experience of our lives—our intrauterine environment, diet, toxins, microbes, allergens, stresses, social connections, thoughts, and beliefs—controls which genes are turned on or off.
It also controls the quality and type of proteins produced by our DNA, as well as what happens to those proteins and how they function once they are produced. More striking is that if your DNA is tagged by an environmental factor, those alterations in genetic expression can be passed down through generations. Her epigenome, which carries increased risk of disease, would then be passed down from generation to generation. Your genes provide the instruction book for all the proteins in your body, which control your physiology and biology.
You may have a genetic predisposition to diabetes or obesity, but you are not predestined. Every moment, you have the power to transform your gene expression and reverse disease by changing the messages and instructions you send to your DNA. For those who are still not convinced and believe that diabetes is genetic, let me tell you the story of the Pima Indians of Arizona. After living for centuries in a harsh desert environment, in the early s they were plunged into a Western culture and food environment.
Their traditional diet was essentially plant-based—whole grains, squash, melons, legumes, beans, and chilies—supplemented by gathered foods, including mesquite, acorns, cacti, chia, herbs, and fish. Although the diet was high in carbohydrates, they were low-glycemic carbs—which means they converted into sugar in their bodies relatively slowly and did not lead to high blood sugar levels. Within one generation, the Pimas switched to a diet rich in sugar, sodas, white flour, trans fats, and processed foods. They went from being thin and fit with no obesity, diabetes, or heart disease in their population to being the second most obese population in the world.
Eighty percent of Arizona Pimas have diabetes by the time they are thirty years old, and they are lucky to live to age forty-six. Pima children as young as three or four are getting adult-onset diabetes and need cardiac bypass surgery by the time they are twenty. The diabesity epidemic in the Pimas is not due to a recent genetic mutation. They sent their ancient, desert-dwelling genes a different set of instructions. Food is not just calories.
You do. This affects not only the poor or Native American populations, but all of us. Obesity takes nine years off the life of the average person, and obesity in adolescents creates the same risk of premature death as heavy smoking. Have no doubt: Diabesity is not a genetic disorder in the strictest sense. The condition is a direct outcome of dietary, lifestyle, and environmental factors turning on all the wrong genes. You can turn these genes off, and The Blood Sugar Solution will show you how. Most of us are taught that diabetes is not reversible and that we are destined to suffer progressive decline in function, including heart disease, kidney failure, blindness, amputation, strokes, and dementia.
We also believe that it is nearly impossible to treat obesity or to be able to maintain long-term weight loss. We think that the only treatment options are to limit the consequences and reduce the complications. However, there is clear evidence from the scientific literature that diabetes is reversible, especially if it is caught in the early stages and treated aggressively through lifestyle intervention and nutritional support, and occasionally with medications. Even most later-stage diabetes can be reversed with very intensive lifestyle changes, medications, and supplements.
A groundbreaking study showed unequivocally that even people with advanced type 2 diabetes, when the pancreas has pooped out and the insulin-producing beta cells are damaged, can recover and diabetes can be reversed in just one week through dramatic changes in diet a very low-glycemic, low-calorie, plant-based diet.
After just one week, they were taken off their medication, proving that diabetes is not a progressive, incurable condition. And the diet was more powerful than medication; yes, it may take a lot of work to reverse diabetes, but your body can heal given the right conditions. But diagnosing problems with insulin resistance and blood sugar control at this point occurs too late in the game.
In fact, your blood sugar is the last thing to go up. Your insulin spikes first , and despite being the simplest way to detect problems early, doctors rarely order the two-hour glucose tolerance test, which measures not only glucose but also insulin levels at fasting and one and two hours after a sugar drink—a much more effective way to catch problems before the onset of disease. I recommend early testing for anyone who has a family history of type 2 diabetes, belly fat or increased waist size, or abnormal cholesterol. The blood sugar quiz at the beginning of the book, and the more detailed diabesity quiz in Part III, can help you understand your risk and act early.
That would be too late. If you have already reached the very late stage of type 2 diabetes when your pancreas has been damaged, you can still experience extraordinary gains in health and vitality if you treat the problem with a whole-systems approach like the one outlined in this book. Remember: Diabetes can be reversed. It is a deadly disease driving our biggest killers—heart attacks, strokes, cancer, dementia, and more. John learned the truth about pre-diabetes the hard way. He was a forty-nine-year-old salesman who had spent his career going from job site to job site.
One day, after ten years of eating fast food on the run, John experienced that dreaded crushing chest and left arm pain. The heart attack got his attention, along with the angiogram and the need for two stents to open his clogged arteries. He came to me wondering what had happened. He thought he was healthy, albeit a little overweight. His diet was pretty typical for an American male—fast food, burgers, fries, sodas, and chips, and he drank at least two beers a day. Over ten years, during which he suffered a stressful relationship and the death of his mother, he gained 50 pounds and his waist went from 32 to 36 inches.
He also had a fatty liver caused by his sugary processed diet. When we looked a little deeper, we found that after a sugar drink which is the best way to test for pre-diabetes and diabetes , his insulin and blood sugar skyrocketed—a clear sign of pre-diabetes. We also found he had dangerous small, dense cholesterol particles, even on Lipitor, and high levels of mercury he lived on the Gulf and ate a lot of fish.
His omega-3 fats EPA and DHA , which help normalize blood sugar, improve insulin sensitivity, and reduce the risk of heart disease, were low even though he ate fish. By the time I saw him, he was on a cabinetful of medication, including a beta-blocker which made him tired , and a whopping 80 mg, or eight times the starting dose, of Lipitor which can cause more insulin resistance and increase the risk of diabetes.
Statins such as Lipitor also lower coenzyme Q10, which is needed for cells to make energy and burn calories. He was put on a blood pressure pill ACE inhibitor and two blood thinners Plavix and aspirin. He lost a few pounds right after his heart attack but still had a long way to go. I put him on The Blood Sugar Solution. Over the course of a year, he went from a fast-food-eating, soda-drinking, pill-popping, big-bellied guy to a thin, fit, healthy man.
He lost 62 pounds and gained 30 years of life. He took up running and got healthier and healthier. We gave him special nutrients to improve insulin sensitivity, including chromium, biotin, alpha lipoic acid, vitamin D3, PGX a special fiber to lower blood sugar, insulin, and cholesterol levels , and fish oil. I also gave him high-dose niacin vitamin B3 to raise his good cholesterol and turn his dangerous small, dense LDL particles into light, large, fluffy ones.
I corrected the deficiency of coenzyme Q We boosted his liver detoxification with n-acetyl-cysteine and helped his body get rid of the mercury. We helped him thin his blood with natural blood thinners. These are better results than any medication can achieve. His fatty liver was healed, and at fifty years old, he was healthier than ever. In fact, one study found that about two-thirds of all patients admitted to the emergency room with heart attacks had pre-diabetes or undiagnosed diabetes. Nothing could be farther from the truth.
It is an earlier stage of diabesity that carries with it nearly all the risks of diabetes. Pre-diabetes can kill you before you ever get to diabetes, through heart attacks, strokes, and even cancer. Just having pre-diabetes can give you pre-dementia. Recent studies have found that as your waist size goes up, the size of your brain goes down. Your brain function is also impaired. One extraordinary brain imaging study by Dr. The problems are happening right now. Insulin treatment in diabetes is a slippery slope, because increased insulin dosage often leads to increased weight gain, higher blood pressure, and elevated cholesterol.
Remember, insulin is a fat storage hormone that also drives appetite and inflammation. Blood sugar improves, but overall risk of heart disease does not. That is why insulin should be the last resort in managing blood sugar and diabetes. And if you have to be on insulin, get on the lowest dose possible. Eating whole, real, fresh food and exercising vigorously will keep your blood sugar low and your insulin needs down.
By understanding and treating all the underlying causes of diabetes, the possibility exists of not only eliminating insulin treatment, but also reversing diabetes and insulin resistance. This is not seen as much in conventional medical care, because the type of diet and lifestyle intervention advice is not adequate or properly designed to create a reversal of diabetes. It is possible with the right treatment approach, based on functional medicine, and new models of group care and community support that teach sustainable behavior change and nutritional life skills including cooking, shopping, exercise, and mind-body skills.
We have to give up on the hope for the magic pill that will fix our problems. Large drug trials have attempted to prove that targeting risk factors such as cholesterol or blood sugar levels with drugs reduces the risk of heart disease, diabetes, and death. Despite hundreds of millions of research dollars spent over many decades, aggressive risk factor treatment of the two most important targets—cholesterol and blood sugar—has consistently failed to show benefit in preventing disease although treatment may be helpful if you have already had a heart attack.
Recent large trials published in the New England Journal of Medicine , , , have confirmed that by treating risk factors with drugs, not only may we be ineffective in preventing heart attacks, diabetes, and death, but we may also be creating harm by ignoring the root causes of disease. Chronic disease is not due to a drug deficiency. High cholesterol is not a Lipitor deficiency. High blood sugar is not an Avandia deficiency. Isolating one risk factor, or even separately treating multiple risk factors, will fail until it is done in the context of addressing the upstream drivers of disease.
Everyone loves the idea of popping a pill to fix the problem. Cardiologists advocate handing out statins at fast-food restaurants. They do work to prevent a second heart attack, but not the first one. The independent Cochrane Collaboration performed a comprehensive review of the research using statins to prevent heart disease by examining fourteen major studies involving 34, patients at low risk for a heart attack.
They found little or no benefit. In addition to the Cochrane Review, many other studies also support this and point out the frequent and significant side effects that come with taking these drugs. In 10—15 percent of the patients who take them, they cause muscle damage, cramps, weakness, and aches; exercise intolerance even in the absence of pain and elevated CPK, or muscle enzymes ; sexual dysfunction; liver and nerve damage; and other problems. They also can cause significant cellular, muscle, and nerve injury and cell death in the absence of symptoms.
A study published in the Journal of the American Medical Association examined five major clinical trials on statins including 32, nondiabetics over 4. During the study period, 2, patients or 8. Those on the highest doses of statins which are increasingly prescribed by physicians were at the highest risk of developing diabetes.
If all doctors followed the latest cholesterol treatment guidelines, and all their patients took their prescribed statin medication, there would be 3. There is no lack of research calling into question the benefits of statins. Should diabetics not try to control their blood sugar?
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Yes, they should. It is clear that elevated blood sugar causes small vessel injury leading to blindness, kidney damage, nerve damage, and cataracts. And the major causes of death in diabetics are heart disease, heart attacks, and strokes. But these problems are best addressed not through medication, but by treating the root causes.
It is the elevated levels of insulin that cause high blood pressure, abnormal cholesterol, and inflammation, not high blood sugars. Lowering your blood sugar without addressing the underlying causes gives you a false sense of security and leads you to believe that you are doing something good to prevent heart attacks and early death. Unfortunately, the evidence shows otherwise. No one profits from lifestyle medicine, so it is not part of medical education or practice. It should be the foundation of our health care system, but doctors ignore it because they get paid to dispense medication and perform surgery.
They should be paid to develop and conduct practice-based and community programs in sustainable lifestyle change. The future of medical care must be to transform general lifestyle guidance—the mandates to eat a healthy diet and get regular exercise that many physicians try to provide to their patients—into individually tailored lifestyle prescriptions for both the prevention and the treatment of chronic diseases. And delivering lifestyle interventions through small groups is the most powerful way to create sustainable behavior change.
Remember, it is easier to get healthy together. Lifestyle is often the best medicine when applied correctly, and it is the only thing that will get us started on the road to reversing this global health crisis. A study in the New England Journal of Medicine showed that surgery and angioplasty for diabetics with heart disease work no better than medication in reducing heart attacks and death, and have higher risks. He had the best medical, pharmaceutical, and surgical care available. Nevertheless, he suffered from very poor health. He went to the emergency room with chest pain and was quickly shuttled into the cath lab for an angiogram.
He was told he needed a cardiac bypass operation, even though research evidence has shown no reduced mortality for cardiac bypass or angioplasty in diabetics. Not providing effective treatment is one thing, but providing harmful, costly, and ineffective treatment like this is unethical. The surgery and subsequent therapy with blood thinners and cholesterol and blood-pressure-lowering medications did not enhance the quality of his health and life.
In fact, he declined rapidly physically and mentally and died of a stroke. It should be our right to have access to proven treatments that provide better value for the individual and for the health care system. Unfortunately, I have seen many patients who gained back all the weight they lost, and more, after gastric bypass. My patient Alan, for instance, had been overweight since he was six years old and never experienced a day without ravenous hunger.
At forty years old, he had a gastric bypass and went from pounds to pounds, but then gained back pounds. At sixty years old, Alan was sick and tired, and he had to deal with all the complications of gastric bypass surgery.
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It often fails, and it can cause many complications, including vomiting and nutritional deficiencies. Clearly, weight loss is critical and important for obtaining optimal health. However, what we are finding in patients who have gastric bypass surgery is that even a dramatic change in diet in a short period of time creates dramatic metabolic changes. All the parameters that we thought were related to obesity, such as high blood sugar, high cholesterol, high blood pressure, inflammation, and clotting, are dramatically reduced even without significant weight loss because of the rapid effects of dietary changes that control which genes get turned on or off.
This is called nutrigenomics— the way food talks to your genes. The converse is also true, as we learned in a study in the New England Journal of Medicine that discussed a woman who had 20 kilos more than 40 pounds of abdominal fat removed by liposuction. She showed no changes in any of her metabolic markers of obesity, including blood sugar, cholesterol, blood pressure, and inflammation. Despite losing 20 kilos, she was still sick.
The take-home message is that the quality of the food we put in our bodies drives our gene function, metabolism, and health. Eating powerful, gene-altering, whole, real, fresh food that you cook yourself can rapidly change your biology. You will lose weight, by getting your systems in balance, not by starving yourself. The Blood Sugar Solution is like getting a gastric bypass without the pain of surgery, vomiting, and malnutrition. Whatever happened to old-fashioned willpower? Everybody knows that the obesity epidemic is a matter of personal responsibility.
People should exercise more self-control. They should avoid overeating and reduce their intake of sugar-sweetened drinks and processed food. New discoveries in science prove that processed, sugar-, fat-, and salt-laden food—food that is made in a plant rather than grown on a plant as Michael Pollan, author of In Defense of Food , would say —is biologically addictive.
No one binges on those foods. Broccoli is not addictive, but chips, cookies, ice cream, and soda can become as addictive as any drug. There are specific biological mechanisms that drive addictive behavior. Nobody chooses to be a heroin addict, cokehead, or drunk. Nobody chooses to have a food addiction either. These behaviors arise from primitive neurochemical reward centers in the brain that override normal willpower and, in the case of food addictions, overwhelm the ordinary biological signals that control hunger.
Why is it so hard for obese people to lose weight despite the social stigma, despite the health consequences such as high blood pressure, diabetes, heart disease, arthritis, and even cancer, and despite their intense desire to lose weight?
It is not because they want to be fat. It is because in the vast majority of cases, certain types of food—processed foods made of sugar, fat, and salt combined in ways kept secret by the food industry—are addictive. We are biologically wired to crave these foods and eat as much of them as possible. If you find yourself scoring 3 or higher, or answering yes to more than two of the questions, you may be suffering from food addiction.
Brain imaging PET scans shows that high-sugar and high-fat foods work just like heroin, opium, or morphine in the brain. Brain imaging PET scans shows that obese people and drug addicts have lower numbers of dopamine receptors, making them more likely to crave things that boost dopamine. This is, in part, genetically determined. People and rats develop a tolerance to sugar—they need more and more of the substance to satisfy themselves; this is true of drugs such as alcohol or heroin.
Obese individuals continue to eat large amounts of unhealthy foods despite severe social and personal negative consequences, just like addicts and alcoholics. Not eating certain types of food or cutting down on certain types of food is something I worry about. I find that when certain foods are not available, I will go out of my way to obtain them.
For example, I will drive to the store to purchase certain foods even though I have other options available to me at home. There have been times when I consumed certain foods so often or in such large quantities that I started to eat food instead of working, spending time with my family or friends, or engaging in other important activities or recreational activities I enjoy. I have had withdrawal symptoms such as agitation, anxiety, or other physical symptoms when I cut down or stopped eating certain foods. Please do not include withdrawal symptoms caused by cutting down on caffeinated beverages such as soda pop, coffee, tea, energy drinks, etc.
I have consumed certain foods to prevent feelings of anxiety, agitation, or other physical symptoms that were developing. Please do not include consumption of caffeinated beverages such as soda pop, coffee, tea, energy drinks, etc. My food consumption has caused significant psychological problems such as depression, anxiety, self-loathing, or guilt. My food consumption has caused significant physical problems or made a physical problem worse.
Over time, I have found that I need to eat more and more to get the feeling I want, such as reduced negative emotions or increased pleasure. What struck me about that film was not that he gained What was surprising was the portrait it painted of the addictive quality of the food. At the beginning of the movie, after he ate his first supersized meal, he threw it up, just like a teenager who drinks too much alcohol at his first party.
The rest of the time he felt depressed, exhausted, anxious, and irritable and lost his sex drive, just like an addict or smoker withdrawing from his drug. The food was clearly addictive. The problem of food addiction is compounded by the fact that food manufacturers refuse to release any internal data on how they put ingredients together to maximize consumption of their products, despite requests from researchers. In his book The End of Overeating , David Kessler, MD, the former head of the Food and Drug Administration, describes the science of how food is made into drugs—through the creation of hyperpalatable foods that lead to neurochemical addiction.
Sugar-sweetened beverages are a unique category of food. And many of these beverages are also loaded with caffeine, which compounds their addictive properties. From to , consumption of calories in sugar-sweetened beverages doubled and is the main source of added sugar calories to our diet. During that time period, obesity rates doubled in children ages two to eleven and tripled in adolescents from ages twelve to nineteen.
More than 90 percent of American children and teenagers drink sodas every day.
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Liquid calories account for up to 10—15 percent of the total daily calorie consumption of the average teenager. The average consumption of sugar-sweetened beverages is calories a day. Each can of soda consumed by children per day increases their risk of being overweight by 60 percent. Those who drank fruit punch doubled their risk of developing diabetes.
Other studies also link sugar-sweetened drinks to pre-diabetes, diabetes particularly in African-Americans , and heart disease. A review of over 30 studies, published in the American Journal of Clinical Nutrition , found clear evidence that drinking sugar-sweetened beverages led to weight gain. A large study by Harvard scientists, funded by the Centers for Disease Control and the Robert Wood Johnson Foundation, found that if people drank water instead of sodas, they would consume fewer calories a day equivalent to about one soft drink.
In a year, that is 82, fewer calories. That amounts to a weight loss of 24 pounds a year just by switching to non-sugar-sweetened drinks. What should we be drinking? Tap water. Filter it, chill it, squeeze a little lemon juice in it, and enjoy it. In fact, researchers found that drinking water before meals increases weight loss by about 44 percent. There is ample proof that sugar-sweetened drinks are harmful to our health. There have been some studies that found little or no association between weight gain and sugar-sweetened beverages.
However, many of these studies were funded by the food industry, including the American Beverage Association formerly known as the American Soft Drink Association. In fact, a review of more than scientific studies found that if the food industry funded the study, there was up to an eightfold likelihood of the study findings proving favorable to the food industry. A little-known fact is that many food industry goliaths banded together to form the Center for Consumer Freedom, which has created a media campaign stating that the obesity epidemic is a hoax.
Investigators discovered that Coca-Cola, PepsiCo, Kellogg, Kraft, and others were behind this but wanted to remain anonymous because, as reported on the website, they are afraid of food fascists—those vegetable-eating, organic-gardening militia groups. Oh my! If you are thinking that diet soft drinks are the answer, think again. Diet drink consumption has increased percent since They may or may not cause cancer, but the evidence is mounting that they lead to weight gain rather than weight loss.
Those who consume diet drinks regularly have a percent increased risk of weight gain, a 36 percent increased risk of pre-diabetes or metabolic syndrome, and a 67 percent increased risk of diabetes. A study of over people found that those who drank two diet sodas a day had five times the increase in waist circumference as those who did not drink soda. Fooling your brain into thinking you are getting something sweet plays dirty tricks on your metabolism. Artificial sweeteners disrupt the normal hormonal and neurological signals that control hunger and satiety feeling full.
A study of rats that were fed artificially sweetened food found that their metabolism slowed down and they were triggered to consume more calories and gain more weight than rats fed sugar-sweetened food. In another alarming study, rats offered the choice of cocaine or artificial sweeteners always picked the artificial sweetener, even if the rats were previously programmed to be cocaine addicts. Your palate shifts from being able to enjoy fruits and vegetables and whole foods to liking only the sexy stuff.
My advice is to give up stevia, aspartame, sucralose, sugar alcohols such as xylitol and malitol, and all of the other heavily used and marketed sweeteners unless you want to slow down your metabolism, gain weight, and become an addict. That buys almost 30 million servings a day or over 10 billion servings a year of corn-sugar-sweetened drinks.
The government our taxes pays now and pays later through ballooning Medicaid and Medicare costs for obesity- and diabetes-driven disease. To whom: the poor or industrial food and agriculture? Now, taxing sugar-sweetened beverages would not eradicate obesity, but liquid calories are proving to be a clear target for public health intervention. Doing this could generate revenue for obesity prevention and treatment programs and reduce soda consumption.
Funds from this initiative could be earmarked for community programs to address obesity in adults and children, especially for the poor. This would cost nothing and have immediate impact. Their own internal studies show that when Coke increased prices by 12 percent, their sales dropped We can alter the default conditions in the environment that foster and promote diabesity and addictive behavior. If pushed, Big Farming can start growing healthy food to feed the nation, and Big Food can come up with innovative solutions that satisfy consumers and supply healthful, economical, convenient, and delicious foods for our world.
However, these industries will not police themselves.
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A meta-analysis of RCTs, which rely on self-reported exercise and are by necessity unblinded, has shown that aerobic endurance training, dynamic resistance training, and isometric training reduce resting SBP and DBP by 3. For additional benefit in healthy adults, a gradual increase in aerobic physical activity to min a week of moderate intensity or min a week of vigorous-intensity aerobic physical activity, or an equivalent combination thereof, is recommended. Smoking is a major risk factor for CVD and cancer. Smoking is second only to BP in contributing risk to the global burden of disease, and smoking cessation is probably the single most effective lifestyle measure for the prevention of CVD, including stroke, myocardial infarction, and PAD.
Most patients will require drug therapy in addition to lifestyle measures to achieve optimal BP control. In the previous Guidelines, five major drug classes were recommended for the treatment of hypertension: ACE inhibitors, ARBs, beta-blockers, CCBs, and diuretics thiazides and thiazide-like diuretics such as chlortalidone and indapamide , based on: i proven ability to reduce BP; ii evidence from placebo-controlled studies that they reduce CV events; and iii evidence of broad equivalence on overall CV morbidity and mortality, with the conclusion that benefit from their use predominantly derives from BP lowering.
These conclusions have since been confirmed by recent meta-analyses. These Guidelines thus recommend that the same five major classes of drugs should form the basis of antihypertensive therapy. There are compelling or possible contraindications for each class of drug Table 20 and preferential use of some drugs for some conditions, as discussed below. There is also evidence that there are differences in the persistence and discontinuation rates of the major drug classes. Other classes of drugs have been less widely studied in event-based RCTs or are known to be associated with a higher risk of adverse effects [e.
These are useful additions to the antihypertensive armamentarium in patients whose BP cannot be controlled by proven combinations of the aforementioned major drug classes. They have similar effectiveness , as each other and other major drug classes on major CV events and mortality outcomes. This result halted further research into the clinical utility of aliskiren for BP treatment. ACE inhibitors are associated with a small increased risk of angioneurotic oedema, especially in people of black African origin and, in such patients, when RAS blockers are used, an ARB may be preferred.
CCBs are widely used for the treatment of hypertension and have similar effectiveness as other major drug classes on BP, major CV events, and mortality outcomes. Though clinically a very relevant event, it is a difficult endpoint to quantify precisely, either because symptoms and signs are relatively non-specific or because oedema due to CCBs may result in misdiagnosis. Comparison with diuretics may also be difficult because fluid loss may mask signs and symptoms of incipient heart failure rather than preventing it.
CCBs have also been compared with other antihypertensive agents in HMOD-based trials, and are reported to be more effective than beta-blockers in slowing the progression of carotid atherosclerosis, and in reducing LVH and proteinuria. CCBs are a heterogeneous class of agents. A smaller number of RCTs have compared non-dihydropyridines verapamil and diltiazem with other drugs, and meta-analyses evaluating the two subclasses vs.
Diuretics have remained the cornerstone of antihypertensive treatment since their introduction in the s. Their effectiveness in preventing all types of CV morbidities and mortality has been confirmed in RCTs and meta-analyses. Chlorthalidone and indapamide have been used in a number of RCTs showing CV benefits, and these agents are more potent per milligram than hydrochlorothiazide in lowering BP, with a longer duration of action compared with hydrochlorothiazide and no evidence of a greater incidence of side effects.
Both thiazide and thiazide-like diuretics can reduce serum potassium and have a side effect profile that is less favourable than RAS blockers, which may account for their association with a higher rate of treatment discontinuation. Potassium may attenuate these effects, and a recent study has shown that the adverse effect of thiazides on glucose metabolism may be reduced by the addition of a potassium-sparing diuretic.
In such circumstances, loop diuretics such as furosemide or torasemide should replace thiazides and thiazide-like diuretics to achieve an antihypertensive effect. RCTs and meta-analyses demonstrate that when compared with placebo, beta-blockers significantly reduce the risk of stroke, heart failure, and major CV events in hypertensive patients. They also exhibit a somewhat less favourable side effect profile than that of RAS blockers, with a higher rate of treatment discontinuation when assessed in real-life conditions. Finally, beta-blockers are not a homogeneous class. In recent years, the use of vasodilating beta-blockers—such as labetalol, nebivolol, celiprolol, and carvedilol—has increased.
Studies on nebivolol have shown that it has more favourable effects on central BP, aortic stiffness, endothelial dysfunction, etc. It has no adverse effect on the risk of new-onset diabetes and a more favourable side effect profile than classical beta-blockers, , including less adverse effects on sexual function.
Bisoprolol, carvedilol, and nebivolol have been shown to improve outcomes in RCTs in heart failure; however, there are no RCTs reporting patient outcomes with these beta-blockers in hypertensive patients. Centrally active drugs were widely used in the earliest decades of antihypertensive treatment when other treatments were not available, but are less frequently used now, principally because of their poorer tolerability relative to the newer major classes of drugs. Antihypertensive drugs, other than the major classes already discussed above, are no longer recommended for the routine treatment of hypertension, and are primarily reserved for add-on therapy in rare cases of drug-resistant hypertension where all other treatment options have failed.
Guidelines have generated a variety of different strategies to initiate and escalate BP-lowering medication to improve BP control rates. In previous Guidelines, the emphasis was on initial use of different monotherapies, increasing their dose, or substituting for another monotherapy. However, increasing the dose of monotherapy produces little additional BP lowering and may increase the risk of adverse effects, whilst switching from one monotherapy to another is frustrating, time consuming, and often ineffective.
For these reasons, more recent Guidelines have increasingly focused on the stepped-care approach, initiating treatment with different monotherapies and then sequentially adding other drugs until BP control is achieved. Despite this, BP control rates have remained poor worldwide. Several reasons need to be considered to identify why the current treatment strategy has failed to achieve better BP control rates: Efficacy of pharmacological therapies.
Are the best available treatments, in whatever combination, incapable of controlling BP in most patients? Physician or treatment inertia. Patient adherence to treatment. Evidence is accumulating that adherence is a much more important factor than previously recognised. Studies using urine or blood assays for the presence or absence of medication have shown that adherence to treatment is low.
Insufficient use of combination treatment. BP is a multiregulated variable depending on many compensating pathways. Consequently, combinations of drugs, working through different mechanisms, are required to reduce BP in most people with hypertension. Thus, monotherapy is likely to be inadequate therapy in most patients.
Complexity of current treatment strategies. There is also evidence that adherence to treatment is adversely affected by the complexity of the prescribed treatment regimen. In a recent study, adherence to treatment was strongly influenced by the number of pills that a patient was prescribed for the treatment of hypertension. The above considerations suggest that the most effective evidence-based treatment strategy to improve BP control is one that: i encourages the use of combination treatment in most patients, especially in the context of lower BP targets; ii enables the use of SPC therapy for most patients, to improve adherence to treatment; and iii follows a treatment algorithm that is simple, applies to all patients, and is pragmatic, with the use of SPC therapy as initial therapy for most patients, except those with BP in the high—normal range and in frail older patients see below.
Among the large number of RCTs of antihypertensive therapy, only a few have directly compared different two-drug combinations, with systematic use of the two combinations in both arms. In other trials, treatment was initiated using monotherapy in either arm and another drug and sometimes more than one drug was added, usually in a non-randomized fashion, according to a pre-specified treatment algorithm. In a few trials, the design precluded the use of what might be considered optimal combinations because multiple monotherapies were being evaluated [e. With this caveat, Table 21 shows that a variety of drug combinations have been used in at least one active arm of placebo-controlled trials and have been associated with significant benefit on major CV events.
In trials comparing different regimens Table 22 , all combinations have been used in a larger or smaller proportion of patients, without major differences in benefits. The only exceptions are two trials in which a large proportion of the patients received either an ARB—diuretic combination or CCB—ACE inhibitor combination, with both regimens being superior to a beta-blocker—diuretic combination in reducing CV outcomes.
However, in six other trials with seven comparisons , beta-blockers followed by diuretics or diuretics followed by beta-blockers were not associated with a significantly different risk of any CV outcome, , , , — and the beta-blocker diuretic combination was significantly more effective than placebo in three trials. Major drug combinations used in trials of antihypertensive treatment in a stepped approach or as a randomized combination combinations vs.
Based on the results of outcome RCTs and recent meta-analyses, and evidence of BP-lowering effectiveness, all five major drug classes can, in principle, be combined with one another, except for ACE inhibitors and ARBs, whose concomitant use may lead to no additional benefit but increased adverse effects and is thus discouraged. These combinations are now widely available in a single pill and in a range of doses, facilitating simplification of treatment, flexible prescribing, and uptitration from lower to higher doses.
These combinations will also limit potential adverse effects associated with diuretic or CCB monotherapy, reducing the risk of hypokalaemia due to diuretics and reducing the prevalence of peripheral oedema due to CCBs. These combinations also ensure that the RAS is inhibited as part of the treatment strategy, which is an important consideration for many patient groups e. Beta-blockers in combination should be preferentially used when there is a specific clinical indication for their use e.
Initial combination therapy is invariably more effective at BP lowering than monotherapy, indeed even low-dose combination therapy is usually more effective than maximal dose monotherapy. Although no RCT has compared major CV outcomes between initial combination therapy and monotherapy, observational evidence suggests that the time taken to achieve BP control is an important determinant of clinical outcomes, especially in higher risk patients, with a shorter time to control associated with lower risk.
In this regard, the outcome of these real-life studies of the impact of initial combination therapy on adherence, BP control, and CV outcomes may be especially relevant. A consideration in the current Guidelines was to persist with the current stepped-care approach to BP treatment, which has been interpreted as recommending monotherapy as initial therapy for most patients, reflecting current practice.
In fact, the previous Guidelines did acknowledge the possibility of initial combination therapy for patients with grade 2 or 3 hypertension, or patients at high or very high risk. In other words, initial monotherapy was only recommended for grade 1 hypertension and low- or moderate-risk patients. Thus, in reality, the shift in emphasis in this new guidance is subtle. However, normalizing the concept of initiating therapy with a two-drug combination for most patients with hypertension is likely to have a major effect on clinical practice and the speed and quality of BP control.
Moreover, the possibility of starting with a low-dose combination of two antihypertensive drugs, even in grade 1 hypertensive patients with low—moderate-risk, is supported by the reduction of CV events obtained by combination therapy in the upper tertile grade 1 hypertension in the HOPE-3 trial.
Studies suggest that two-drug combination therapy will control BP in approximately two-thirds of patients. We do not recommend three-drug combinations as initial therapy. It is further supported by data from recent studies using various methods to assess adherence to treatment, including the quantification of antihypertensive drugs in urine and blood, , and estimates such as pill counting or prescription refills, which, although indirect, allow the measurement of adherence on a prolonged basis, thereby accounting for its time-variable nature.
This approach is now facilitated by the availability of several SPCs with a range of dosages, which eliminates the often-stated disadvantage of SPC therapy i. It is also convenient that the most widely available SPCs mirror the major drug class combinations recommended by these Guidelines.
The major advantage of an SPC as the usual therapeutic approach for hypertension is that patients can progress from 1, 2, or 3 drug treatments whilst remaining on a simple treatment regimen with a single pill throughout, increasing the likelihood of adherence to therapy and achieving BP control. Although, at present, the availability of two-drug SPCs is largely limited to a RAS blocker with either a CCB or diuretic, it would be desirable to see the development of an expanded range of low-cost SPCs in different drug formulations, tailored to different clinical requirements.
Polypills have also emerged as SPCs i. Studies of bioequivalence suggest that when combined in the polypill, different agents maintain all or most of their expected effect. Nevertheless, the advantage of treatment simplification and adherence suggests that use of the polypill may be considered in patients with hypertension as substitution therapy, when the need and effectiveness of each polypill component has been previously established by their administration in separate tablets.
When BP remains uncontrolled with three-drug combination therapy, the patient is classified as having resistant hypertension, assuming that secondary causes of hypertension and poor adherence to treatment have been excluded, and that the elevation in BP has been confirmed by repeated office BP measurement, ABPM, or HBPM see section 8. Such patients should be considered for specialist evaluation.
Reflecting on the evidence above, and recognizing the urgent need to address the factors contributing to the poor control of BP in treated hypertensive patients see section 7. A beta-blocker in combination with a diuretic or any drug from the other major classes is an alternative when there is a specific indication for a beta-blocker, e.
The addition of spironolactone for the treatment of resistant hypertension, unless contraindicated see section 8. The use of other classes of antihypertensive drugs in the rare circumstances in which BP is not controlled by the above treatments. Information on availability and recommended doses of individual drugs, as well as SPCs and free combinations, can be found in national formularies.
The algorithm recommends initial therapy for most patients with a two drug-combination, ideally as an SPC. Variations from the core drug treatment algorithm for uncomplicated hypertension shown in Figure 4 are specified in Figures 5 to 8. Recommended BP target ranges for treated hypertension are shown in Table Refers to patients with previous stroke and does not refer to blood pressure targets immediately after acute stroke.
Treatment decisions and blood pressure targets may need to be modified in older patients who are frail and independent. Core drug treatment strategy for uncomplicated hypertension. Drug treatment strategy for hypertension and coronary artery disease. Drug treatment strategy for hypertension and chronic kidney disease. Drug treatment strategy for hypertension and hear failure with reduced ejection fraction. Do not use non-dihydropyridine CCBs e. Consider a loop diuretic as an alternative in patients with oedema. Drug treatment strategy for hypertension and atrial fibrillation.
The drug treatment strategy for patients with hypertension should be based on the algorithm shown Figures 4 to 8 , unless there are contraindications to these drugs Table 20 , or concomitant conditions or diseases are present that require specific modification of the drugs, as outlined in the recommendations below. Various device-based therapies have emerged, principally targeted at the treatment of resistant hypertension.
These are discussed below. Carotid baroreceptor stimulation or baroreflex amplification therapy—externally via an implantable pulse generator or internally via an implantable device designed to increase the strain on the carotid bulb—can lower BP in patients with resistant hypertension. An RCT with the first generation of an implantable pulse generator showed sustained BP-lowering efficacy and sympathetic nervous system inhibition , but with some concerns about procedural and longer term safety.
A propensity score-matched comparison of the first- and second-generation systems revealed that BP at 12 months post-implantation was similar, with a better safety profile for the second-generation device. Another consideration is that implantation is costly and requires a complex surgical intervention. This has led to the development of an endovascular carotid baroreflex amplification device using a dedicated stent-like device designed to stretch the carotid bulb and increase baroreflex sensitivity.
Preliminary data in humans have shown evidence of BP-lowering efficacy of this new approach, but data from ongoing RCTs are needed to definitively understand its longer-term efficacy and safety. The rationale for renal denervation lay with the importance of sympathetic nervous system influences on renal vascular resistance, renin release, and sodium reabsorption, the increased sympathetic tone to the kidney and other organs in hypertensive patients, and the pressor effect of renal afferent fibres documented in experimental animals.
Several observational studies and national and international registries support the BP-lowering efficacy of renal denervation originally reported in the Symplicity HTN-1 and HTN-2 trials. The PRAGUE study documented similar effects between renal denervation and optimized pharmacotherapy mainly by adding spironolactone with respect to BP-lowering efficacy; however, the latter was associated with more side effects and high discontinuation rates.
Beyond resistant hypertension, interim data in the first 80 patients treated with renal denervation but with no background antihypertensive therapy showed a modest effect of renal denervation vs. Evaluating the efficacy of renal denervation has been challenging because the procedure needs to be applied to a population with a high probability of BP response.
This is complicated by i the complex pathophysiology of hypertension, ii the lack of clinically applicable measures of sympathetic activity, iii the absence of predictors of the long-term BP response following renal denervation, and iv the absence of reliable markers of procedural success to immediately establish whether denervation has been achieved.
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Except for rare problems related to the catheterization procedure access site complications, vessel dissection, etc. Major uncertainties remain as to the clinical role of renal denervation outside of clinical studies, which should be performed in carefully selected patients at specialist hypertension centres and by experienced operators. The central iliac arteriovenous anastomosis creates a fixed-calibre 4 mm conduit between the external iliac artery and vein using a stent-like nitinol device ROX arteriovenous coupler.
Some important safety aspects need to be considered. There were no reports of right heart failure or high-output cardiac failure after device implantation over the short-term, but longer follow-up is clearly needed. The carotid body is located at the bifurcation of the common carotid. It is innervated by nerve fibres from the vagus nerve through the cervical ganglion and the carotid sinus nerve.
Surgical resection of the carotid body is associated with reductions in BP and sympathetic overactivity in patients with heart failure. In summary, device-based therapy for hypertension is a fast-moving field. Further sham-controlled studies are needed before device-based therapies can be recommended for the routine treatment of hypertension outside of the framework of clinical trials.
The recommended treatment strategy should include appropriate lifestyle measures and treatment with optimal or best-tolerated doses of three or more drugs, which should include a diuretic, typically an ACE inhibitor or an ARB, and a CCB. Pseudo-resistant hypertension see below and secondary causes of hypertension should also have been excluded see section 8. After applying a strict definition see above and having excluded causes of pseudo-resistant hypertension see section 8.
Poor office BP measurement technique , including the use of cuffs that are too small relative to the arm circumference, can result in a spurious elevation of BP. Marked brachial artery calcification , especially in older patients with heavily calcified arteries. Clinician inertia , resulting in inadequate doses or irrational combinations of BP-lowering drug therapies. Other causes of resistant hypertension Lifestyle factors, such as obesity or large gains in weight, excessive alcohol consumption, and high sodium intake.
Intake of vasopressor or sodium-retaining substances, drugs prescribed for conditions other than hypertension, some herbal remedies, or recreational drug use cocaine, anabolic steroids, etc. Resistant hypertension characteristics, secondary causes, and contributing factors adapted from reference A physical examination, with a particular focus on determining the presence of HMOD and signs of secondary hypertension.
Laboratory tests to detect electrolyte abnormalities hypokalaemia , associated risk factors diabetes , organ damage advanced renal dysfunction , and secondary hypertension. Patients should be screened for a secondary cause of hypertension, especially primary aldosteronism or atherosclerotic renal artery stenosis, particularly in older patients or patients with CKD.
Poor adherence to treatment should be considered, but its identification may be challenging in routine clinical practice. Effective treatment combines lifestyle changes especially the reduction of sodium intake , discontinuation of interfering substances, and the sequential addition of antihypertensive drugs to the initial triple therapy. Ultimately, replacing all current drugs by a simpler treatment regimen using SPC treatment is recommended to reduce pill burden and improve adherence to treatment.
The optimal drug treatment of resistant hypertension has been poorly studied. The most effective strategy seems to be additional diuretic treatment to decrease volume overload, together with the restriction of salt intake, particularly in patients with CKD. BP control may be improved by increasing the dose of the existing diuretic or by switching to a more potent thiazide-like diuretic chlorthalidone or indapamide. Although resistant hypertension may show a BP reduction if the existing diuretic dose is further increased, most patients require the administration of additional drugs.
Moreover, the efficacy and safety of spironolactone for the treatment of resistant hypertension has not yet been established in patients with significant renal impairment. Moreover, electrolytes and eGFR should be monitored soon after initiation and at least annually thereafter.
Neither was as effective as spironolactone, but they did reduce BP significantly vs. Direct vasodilators, such as hydralazine or minoxidil, are infrequently used because they may cause severe fluid retention and tachycardia. New BP-lowering drugs nitric oxide donors, vasopressin antagonists, aldosterone synthase inhibitors, neutral endopeptidase inhibitors, and endothelin antagonists are all under investigation.
When spironolactone is not tolerated, replace with amiloride or eplerenone. Secondary hypertension is hypertension due to an identifiable cause, which may be treatable with an intervention specific to the cause. A high index of suspicion and early detection of secondary causes of hypertension are important because interventions may be curative, especially in younger patients [e.
Interventions that treat the cause of secondary hypertension later in life are less likely to be curative i. Screening all hypertensive patients for secondary hypertension is not feasible or cost-effective; however, there are some general patient characteristics that suggest those more likely to have secondary hypertension and in whom screening should be considered after confirming that BP is elevated with ABPM Table It is beyond the scope of these Guidelines to describe the detailed clinical management of specific causes of secondary hypertension.
However, the commoner causes of secondary hypertension, clinical history, and screening tests are described in Table 26 , and the typical age distribution of these causes of secondary hypertension is shown in Table Review of these tables demonstrates that most screening can be undertaken with blood and urine tests, abdominal ultrasound, and echocardiography.
Referral to a specialist centre is recommended for additional investigations to confirm a suspected diagnosis of secondary hypertension and for clinical management. Other causes of secondary hypertension due to drugs and substances, and rarer monogenic causes, are described below and are summarized in Tables 28 and Medications and other substances that may increase blood presssure Medications and other substances may cause a sufficient increase in BP to raise the suspicion of secondary hypertension Table Consequently, a careful drug history is important when considering a diagnosis of secondary hypertension.
Moreover, other commonly used drugs such as non-steroidal anti-inflammatory drugs or glucocorticoids can antagonize the BP-lowering effect of antihypertensive medications in patients treated for hypertension, and may contribute to a loss of BP control. Genetic causes of secondary hypertension are usually due to single-gene disorders see section 6. Thus, they are usually associated with a suppressed plasma renin concentration PRC or plasma renin activity PRA , which is unusual in younger patients and especially those treated with antihypertensive medications e.
Thus, the finding of a suppressed PRC or PRA, especially whilst taking these drugs, should raise the suspicion of secondary hypertension due a salt-retaining state. Importantly, beta-blockers in particular, but also non-steroidal anti-inflammatory drugs, alpha-methyl dopa, or clonidine, suppress PRC and PRA. Hypertension emergencies are situations in which severe hypertension grade 3 is associated with acute HMOD, which is often life-threatening and requires immediate but careful intervention to lower BP, usually with intravenous i.
The hallmark of this condition is small artery fibrinoid necrosis in the kidney, retina, and brain. Patients with severe hypertension associated with other clinical conditions who are likely to require an urgent reduction of BP, e. Patients with sudden severe hypertension due to phaeochromocytoma , associated with organ damage. The most common emergency symptoms will depend of the organs affected but may include headache, visual disturbances, chest pain, dyspnoea, dizziness, and other neurological deficits.
In patients with hypertensive encephalopathy, the presence of somnolence, lethargy, tonic clonic seizures, and cortical blindness may precede a loss of consciousness; however, focal neurological lesions are rare and should raise the suspicion of stroke. Acute stroke , especially intracerebral haemorrhage, when associated with severe hypertension has often been termed a hypertension emergency, but a more cautious approach is now recommended for acute BP lowering in the emergency setting of acute stroke see section 8.
However, these patients will require urgent outpatient review to ensure that their BP is coming under control. Acute and severe increases in BP can sometimes be precipitated by ingestion of sympathomimetics such as meta-amphetamine or cocaine. This can result in a hypertension emergency when there is evidence of acute HMOD. It is emphasized that many patients in an emergency department with acute pain or distress may experience an acute elevation in BP that will be restored to normal when the pain and distress are relieved, rather than requiring any specific intervention to lower BP.
For patients with a suspected hypertension emergency, a diagnostic workup is shown in Table Apart from acute BP lowering in stroke, there are no RCTs evaluating different treatment strategies for hypertensive emergencies. The key considerations in defining the treatment strategy are: Establishing the target organs that are affected, whether they require any specific interventions other than BP lowering, and whether there is a precipitating cause for the acute rise in BP that might affect the treatment plan e. The type of BP-lowering treatment required.
With regard to drug treatment, in a hypertension emergency, i. Recommended drug treatments for specific hypertension emergencies , are shown in Table 31 and an expanded range of possible drug choices is shown in Table Rapid uncontrolled BP lowering is not recommended as this can lead to complications. Hypertensive emergencies requiring immediate blood pressure lowering with intravenous drug therapy. Although i. However, low initial doses should be used because these patients can be very sensitive to these agents and treatment should take place in hospital.
Further comprehensive details on the clinical management of hypertension emergencies are available. The survival of patients with hypertension emergencies has improved dramatically over past decades, but these patients remain at high risk , and should be screened for secondary hypertension see section 8. After discharge from hospital, when BP has reached a safe and stable level on oral therapy, we recommend frequent, at least monthly, visits in a specialized setting until the optimal target BP is achieved and long-term specialist follow-up thereafter.
As discussed in section 4, white-coat hypertension is defined as an elevated office BP despite a normal out-of-office BP. Compared with normotensive people, white-coat hypertension is associated with an increased prevalence of dysmetabolic risk factors and asymptomatic organ damage. It is also associated with a greater risk of developing type 2 diabetes and sustained hypertension, as well as an overall increased risk of CV events. Office and out-of-office BP both home and ambulatory BP should be measured frequently, e. Treatment should consider lifestyle changes to reduce the elevated CV risk.
Whether or not patients with white-coat hypertension should receive antihypertensive drugs is unresolved. In white-coat hypertension, antihypertensive drugs have been shown to effectively and persistently lower office BP, with no concomitant reduction indeed, even a small increase of ambulatory BP values. However, it should be considered that people with white-coat hypertension have inevitably been well represented in trials documenting the protective effect of antihypertensive drugs, particularly those addressing conditions in which white-coat hypertension is more common, such as grade 1 hypertension or hypertension in older patients.
As reported in section 4. Such people usually have dysmetabolic risk factors and asymptomatic organ damage, which are substantially more frequent than in people who are truly normotensive. Masked hypertension is commoner in younger rather than older individuals, and in those with an office BP in the borderline hypertension range i.
Masked hypertension is associated with progression to sustained office hypertension, increased frequency of developing type 2 diabetes, and the presence of HMOD. The long-term risk of fatal and non-fatal CV events approaches that of patients with sustained hypertension. CV risk factors including organ damage and ideally both home and ambulatory BP should then be periodically monitored. Factors contributing to the out-of-office BP elevation e.
The impact of antihypertensive drug treatment on CV outcomes in people with masked hypertension has never been studied. Nevertheless, treatment with BP-lowering medication should be considered because these patients are at high CV risk, often have HMOD, and the adverse prognostic importance of out-of-office BP elevations has been well documented. Presently, no data are available from outcome trials for patients with MUCH; however, mindful of their high CV risk, treatment uptitration should be considered to ensure that that both office and out-of-office BP are controlled.
The prevalence of hypertension increases with age. Most hypertension across the age span is due to systolic hypertension; however, elevations of DBP and isolated diastolic hypertension, when they occur, are more common in younger rather than older patients. All younger adults with grade 2 or more severe hypertension should be offered lifestyle advice and drug treatment, as well as high-risk younger adults with grade 1 hypertension i.
There is controversy about whether younger adults with uncomplicated grade 1 hypertension should be treated because of the obvious difficulty in conducting conventional clinical outcome trials in younger adults in whom the outcomes only occur after many years. Thus, despite the absence of RCT evidence demonstrating the benefits of antihypertensive treatment in younger adults with uncomplicated grade 1 hypertension, treatment with BP-lowering drugs may be considered prudent. If a decision is taken not to offer treatment or treatment is declined, lifestyle advice should be prescribed, and longer-term follow-up is essential as BP will invariably rise.
Other interventions, e. Some young, healthy people, and men in particular, may present with isolated grade 1 systolic hypertension i. A recent examination of prospective data from the Chicago Heart Association Detection Project found that young men with isolated systolic hypertension had a CV risk similar to that of individuals with high—normal BP and that isolated systolic hypertension in the young was closely associated with smoking.
For many years, advanced age has been a barrier to the treatment of hypertension because of concerns about potential poor tolerability, and even harmful effects of BP-lowering interventions in people in whom mechanisms preserving BP homeostasis and vital organ perfusion may be more frequently impaired. This approach is not appropriate, because evidence from RCTs has shown that in old and very old patients, antihypertensive treatment substantially reduces CV morbidity and CV and all-cause mortality , see section 7.
Moreover, treatment has been found to be generally well tolerated. However, older patients are more likely to have comorbidities such as renal impairment, atherosclerotic vascular disease, and postural hypotension, which may be worsened by BP-lowering drugs. Older patients also frequently take other medications, which may negatively interact with those used to achieve BP control.
A further important caveat is that RCTs have not included very frail patients, dependent patients, and patients with postural hypotension. It is thus uncertain whether, and to what extent, such patients would benefit from BP-lowering treatment in the context of their comorbidities and reduced life expectancy. That said, age alone must never be a barrier to treatment because high BP is an important risk factor even at the most advanced ages.
It is recommended that older patients are treated according to the treatment algorithm outlined in section 7. In very old patients, it may be appropriate to initiate treatment with monotherapy. In all older patients, when combination therapy is used, it is recommended that this is initiated at the lowest available doses.
In all older patients, and especially very old or frail patients, the possible occurrence of postural BP should be closely monitored and symptoms of possible hypotensive episodes checked by ABPM. Unless required for concomitant diseases, loop diuretics and alpha-blockers should be avoided because of their association with injurious falls.
A key emphasis in treating older patients, and especially the very old, is to carefully monitor for any adverse effects or tolerability problems associated with BP-lowering treatment, keeping in mind that adverse effects can be more frequent than reported in RCTs, in which specific medical expertise and close patient supervision may minimize adverse effects and tolerability problems.
An important consideration is frail, dependent older patients, including those with orthostatic hypotension. These have been excluded from RCTs. The SPRINT trial showed the benefits of BP-lowering treatment being extended to recruited patients who were at the frailer end of the spectrum, including those with reduced gait speed.
In some patients, the best achievable BP may be higher than the recommended target, but it should be recognised that any amount of BP lowering is likely to be worthwhile and associated with a reduced risk of major CV events especially stroke and heart failure and mortality. Maternal risks include placental abruption, stroke, multiple organ failure, and disseminated intravascular coagulation. Hypertension in pregnancy is not a single entity but comprises: Pre-existing hypertension: precedes pregnancy or develops before 20 weeks of gestation, and usually persists for more than 6 weeks post-partum and may be associated with proteinuria.
Gestational hypertension: develops after 20 weeks of gestation and usually resolves within 6 weeks post-partum. Pre-existing hypertension plus superimposed gestational hypertension with proteinuria. It occurs more frequently during the first pregnancy, in multiple pregnancy, in hydatidiform mole, in antiphospholipid syndrome, or with pre-existing hypertension, renal disease, or diabetes. It is often associated with foetal growth restriction due to placental insufficiency and is a common cause of prematurity. Antenatally unclassifiable hypertension: this term is used when BP is first recorded after 20 weeks of gestation and it is unclear if hypertension was pre-existing.
Reassessment 6 weeks post-partum will help distinguish pre-existing from gestational hypertension. BP in pregnancy should be measured in the sitting position or the left lateral recumbent during labour with an appropriately sized arm cuff at heart level and using Korotkoff V for DBP. Manual auscultation remains the gold standard for BP measurement in pregnancy, because automated devices tend to under-record the BP and are unreliable in severe pre-eclampsia. Only validated devices should be used in pregnancy. ABPM helps avoid unnecessary treatment of white-coat hypertension, and is useful in the management of high-risk pregnant women with hypertension and those with diabetic or hypertensive nephropathy.
Basic laboratory investigations recommended for monitoring pregnant hypertensive women include urine analysis, blood count, haematocrit, liver enzymes, serum creatinine, and serum uric acid increased in clinically evident pre-eclampsia. Hyperuricaemia in hypertensive pregnancies identifies women at increased risk of adverse maternal and foetal outcomes. All pregnant women should be assessed for proteinuria in early pregnancy to detect pre-existing renal disease and, in the second half of pregnancy, to screen for pre-eclampsia. In addition to basic laboratory tests, the following investigations may be considered: Ultrasound investigation of the kidneys and adrenals, and plasma or urinary fractionated metanephrine assays in pregnant women with a history suggestive of phaeochromocytoma.
Doppler ultrasound of uterine arteries performed after 20 weeks of gestation to detect those at higher risk of gestational hypertension, pre-eclampsia, and intrauterine growth retardation. Women at high or moderate-risk of pre-eclampsia should be advised to take — mg of aspirin daily from weeks 12— Moderate-risk of pre-eclampsia includes one or more of the following risk factors: First pregnancy. The goal of drug treatment of hypertension in pregnancy is to reduce maternal risk; however, the agents selected must be safe for the foetus. The benefits of drug treatment for mother and foetus in hypertension in pregnancy have not been extensively studied, with the best data from a single trial using alpha-methyldopa, performed 40 years ago.
However, secondary analysis suggested that tighter control of BP may reduce the risk of developing more severe hypertension and pre-eclampsia. Most women with pre-existing hypertension and normal renal function will not have severe hypertension and are a low risk for developing complications during pregnancy. Indeed, some of these women may be able to withdraw their medication in the first half of pregnancy because of the physiological fall in BP.
Women with pre-existing hypertension may continue their current antihypertensive medication, but ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated due to adverse foetal and neonatal outcomes. Methyldopa, labetalol, and CCBs are the drugs of choice.
Beta-blockers may induce foetal bradycardia; consequently, if used, their type and dose should be carefully selected, with atenolol best avoided. Diuretic therapy is generally avoided because plasma volume is reduced in women who develop pre-eclampsia. There are no data to define the optimal BP treatment target in pregnant women.
Nevertheless, for pragmatic reasons, if treatment is initiated it is important to suggest a treatment target to calibrate how much treatment to give. The selection of the antihypertensive drug and its route of administration depends on the expected time of delivery. Pharmacological treatment with i. Intravenous hydralazine is no longer the drug of choice as it is associated with more perinatal adverse effects than other drugs. Intravenous urapidil can also be considered.
In hypertensive crises, i. Both labetalol and nicardipine have shown to be safe and effective for the treatment of severe pre-eclampsia if i. BP-lowering therapy is necessary. Intravenous sodium nitroprusside is contraindicated in pregnancy because of an increased risk of foetal cyanide poisoning. The drug of choice when pre-eclampsia is associated with pulmonary oedema is nitroglycerin glyceryl trinitrate , given as an i.
Delivery is indicated i urgently in pre-eclampsia with visual disturbances or haemostatic disorders, and ii at 37 weeks in asymptomatic women. Post-partum hypertension is common in the first week. Any drug recommended can be used according to the hypertension treatment algorithm shown in Figure 4 , with the caveats: i methyldopa should be avoided because of the risk of post-partum depression and ii consideration should be given to drug choice in breastfeeding women. All antihypertensive drugs taken by the nursing mother are excreted into breast milk.
Most are present at very low concentrations except for propranolol and nifedipine, with breast milk concentrations similar to those in maternal plasma. Reference to prescribing information in breastfeeding women is important.
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Women experiencing hypertension in their first pregnancy are at increased risk in a subsequent pregnancy. The earlier the onset of hypertension in the first pregnancy, the higher the risk of recurrence in a subsequent pregnancy. Women who develop gestational hypertension or pre-eclampsia are at increased risk of hypertension, stroke, and ischaemic heart disease in later adult life.
Therefore, annual visits to a primary care physician to check BP and metabolic factors are recommended for these patients. Further detail on the management of hypertension and other CV disorders in pregnancy is available. The rise in BP appears to be related to the oestrogen content and may be less likely with the progestogen-only oral contraceptive pill. Older studies have demonstrated a relationship between the oral contraceptive pill and venous thrombosis and venous thromboembolism, and, to a lesser extent, myocardial infarction especially with concomitant smoking history and stroke.
Thus, the use of oral contraceptives should consider the risks and benefits for the individual patient. Changes in BP should be carefully evaluated with follow-up readings. In such patients, alternative forms of contraception should be offered. Discontinuation of combined oestrogen—progestin oral contraceptives in women with hypertension may improve their BP control. Cross-sectional studies have long established that menopause doubles the risk of developing hypertension, even after adjusting for factors such as age and BMI.
In summary, current evidence suggests that the use of hormone-replacement therapy is not associated with an increase in BP. Moreover, it is not contraindicated in women with hypertension, and women with hypertension may be prescribed hormone-replacement therapy as long as BP levels can be controlled by antihypertensive medication. In comparison with the non-black population, hypertension is more prevalent in the black population living in Europe, similarly to that reported for the USA. Afro-American US patients, in contrast to the much scarcer database available for European black people, and thus we extrapolate from US data.
However, this extrapolation requires some caution as differences between the North American and the European black population exist, especially with regard to socioeconomic status, CV risk, , and the response to antihypertensive drug treatment. However, to achieve an effective BP reduction and BP control, salt restriction is particularly important in black patients, in whom it may lead to greater BP falls and more favourably impact on the effectiveness of BP-lowering drug treatment.
Angioedema appears more common with ACE inhibitors in black patients, which may favour the preferred use of ARBs in this population. Despite some progress in recent years, data on hypertension prevalence, management, and control in European black patients and in other immigrant populations such as European individuals from South Asia are still scarce, , which makes this field an important area for future research. There is no evidence that the BP response to treatment in other ethnic groups differs from that reported in the general population in Europe.
Except in patients with low grade 1 hypertension or frail older patients, in whom initial treatment with a single drug may be more appropriate. High BP is a common feature of type 1 and, particularly, type 2 diabetes. Moreover, masked hypertension and a blunted nocturnal fall in BP are not infrequent in people with diabetes. Substantial evidence supports the benefits of BP reduction in people with diabetes to reduce major macrovascular and microvascular complications of diabetes, as well as reducing mortality.
Proven benefits of BP-lowering treatment in diabetes also include a significant reduction in the rate of end-stage renal disease, , retinopathy, 1 and albuminuria. When considering treatment for hypertension, it is important to exclude significant postural hypotension, which can be marked in people with diabetes due to autonomic neuropathy.
This approach ensures that the treatment strategy includes an ACE inhibitor or ARB, which has been shown to reduce albuminuria and the appearance or progression of diabetic nephropathy more effectively than other drug classes. Recent RCTs have shown that some antidiabetes agents the selective inhibitors of sodium glucose cotransporter 2 in the kidney can reduce office and ambulatory BP by several mmHg, , and that this occurs even when people are treated with antihypertensive drugs.
This may help improve BP control see below , which is especially difficult in diabetes, and may reduce the progression of CKD — see also section 8. There has been considerable debate about the target BP that should be achieved in people with diabetes see section 7. BP targets for renoprotection for patients with diabetic kidney disease are discussed in section 8. A recent meta-analysis has shown that BP lowering significantly reduced end-stage renal disease in patients with CKD, but only in those with albuminuria and without any beneficial effect on CV events.
Reduction of albuminuria has also been considered as a therapeutic target. Analyses of data from RCTs have reported that changes in urinary albumin excretion are predictors of renal and CV events. The combination of two RAS blockers is not recommended. Lifestyle advice, especially sodium restriction, may be especially effective at aiding BP lowering in patients with CKD. Thus, careful monitoring of blood electrolytes and eGFR is essential, but clinicians should not be alarmed by the anticipated decline in GFR when treatment is initiated. This decline usually occurs within the first few weeks of treatment and stabilizes thereafter.
If the decline in GFR continues or is more severe, the treatment should be stopped, and the patient investigated to determine the presence of renovascular disease. Hypertension is the most frequent comorbidity in patients with COPD, and coincidence of the two diseases may affect 2. The presence of COPD also has an impact on the selection of antihypertensive drugs, which should consider their effects on pulmonary function.
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