Posted on Leave a comment

Venous leg ulcer prevention: Identifying patients who are at risk


Ulceration of the lower limbs results in painful and often debilitating leg wounds that can have a profound effect on patients’ physical, social and psychological wellbeing. It is estimated that the UK spends nearly £2bn each year managing lower limb ulceration but NHS England has highlighted that the care patients receive is often sub-optimal and unwarranted variation results in higher costs and longer healing times. Rates of non-healing are both common and costly, which adds to the burden on patients and the healthcare system. The prevalence of leg ulceration is higher in older age groups and, as our population ages, the problem is likely to increase. All nurses have a vital role in identifying patients at risk of ulceration and supporting them to take preventative action to prevent skin breakdown. This article, the first in a three-part series on the prevention of leg ulceration, looks at how nurses can identify at-risk patients.



Lower-leg ulceration affects around 1.5% of adults in the UK, with 730,000 people having often painful and debilitating leg wounds (Guest et al, 2015). Prevalence is highest among people aged 60-80 years, and increases with age (Farah and Davis, 2010), so the ageing population signals a growing problem.

Approximately 70% of lower-leg ulceration relates to venous disease (Casey, 2004), a debilitating condition affecting millions of people worldwide (O’Donnell et al, 2014). Varicose veins are often a first sign of venous disease and are a predictive factor in developing ulceration (Robertson et al, 2011) (Fig 1). The incidence of varicose veins in the adult population ranges from 10% to 60% worldwide (Selçuk Kapısız et al, 2014), and is estimated at 36% in the UK (Robertson, 2013; Evans et al, 1999).


Compression therapy has an important role to play in the prevention of leg ulceration but a greater emphasis on prevention is needed if the considerable burden of managing leg ulceration is to be reduced. Nurses should actively assess patients’ legs for signs of venous disease and oedema, and undertake opportunistic assessment whenever possible. Ensuring appropriate early intervention will improve patient outcomes and result in significant cost savings to health services.

Key points

*Lower-leg ulceration affects 1.5% of adults in the UK, and an ageing population means the number is likely to grow
*Prevention and management are often sub-optimal, leading to non-healing and a near doubling of patients each year
*Venous leg ulceration is the most severe manifestation of chronic venous disease caused by venous hypertension
*Skin changes are the biggest predictor of ulceration, with lower-limb oedema also being a risk
*Nurses need to spot the early signs of venous leg ulceration and take preventative action, such as using compression therapy



D’OXYVA® (deoxyhemoglobin vasodilator) has eliminated 97%* of all mild to severe so-called spider and varicose veins for both men and women users. Doing so while eliminating associated long-term pain within 2 to 4 weeks** by taking a single 5-minute application 5 times per week.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

Diabetes, cardiovascular disease and the microcirculation


Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot be accounted for by conventional cardiovascular risk factors. Hypertension occurs in majority of people with T2DM, which is substantially more frequent than would be anticipated based on general population samples. The impact of hypertension is considerably higher in people with diabetes than it is in the general population, suggesting either an increased sensitivity to its effect or a confounding underlying aetiopathogenic mechanism of hypertension associated with CVD within diabetes. In this contribution, we aim to review the changes observed in the vascular tree in people with T2DM compared to the general population, the effects of established anti-diabetes drugs on microvascular outcomes, and explore the hypotheses to account for common causalities of the increased prevalence of CVD and hypertension in people with T2DM.


Type 2 diabetes mellitus (T2DM) and hypertension are established risk factors for cardiovascular disease (CVD), and people with T2DM and hypertension have an increased risk of cardiovascular (CV) mortality compared with those with either condition alone. This excess risk is suggested to be due to the synergistic effect on large and small blood vessels simultaneously, thereby reducing the potential for compensatory collateralization protecting organs from the adverse consequences of damage to either vascular bed. The principle role of the vasculature is to deliver oxygen and nutrients to the tissues—whether that is the heart, the brain, or the kidney. The functional changes occurring in T2DM and hypertensive conditions significantly alter the haemodynamic stress on the heart and other organs. However, the different physiology, mechanisms and changes at the microvascular level differ from those at the macrovascular level in T2DM and hypertension, which in turn have significant implications with respect to future CV risk.


Over the past few decades, epidemiological studies have elucidated the role of impaired microcirculation in people with diabetes and aetiopathogenesis of CVD. This has led to the recognition of the prevalence of microvascular disease. Furthermore, the prognostic value of incidence of microvascular disease in predicting CVD is now acknowledged. The focus of present-day epidemiological studies is to understand the association between pathological mechanisms and the risk factors to ascertain whether they are targets of therapeutic value or risk markers of CVD. These studies have contributed to the evidentiary framework in favour of clinical monitoring of microvascular function, and spurred the initiation of mechanistic studies by redefining our knowledge of vascular disease, particularly in people with diabetes.


Over the past few decades, epidemiological studies have elucidated the role of impaired microcirculation in people with diabetes and aetiopathogenesis of CVD. D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

Older adults more likely to develop dementia after a concussion, Canadian study finds


Older adults are much more likely to develop dementia after experiencing a concussion, according to a large new Canadian study. But the researchers also found this risk may be modestly reduced by taking a certain group of cholesterol-lowering drugs.

The study, published on Monday in the journal JAMA Neurology, found one in six Ontarians, ages 65 and older, were diagnosed with dementia within an average of four years after suffering a concussion. That was double the rate for the rest of the population.

The study, however, found that concussion patients who took statins, a class of drugs commonly used to prevent heart disease, had about 10 to 15 per cent lower risk of dementia than those who did not.

While this suggests statins may help patients’ brains recover after a concussion, the findings underscore the importance of protecting one’s brain in the first place, says lead investigator Donald Redelmeier, a senior scientist at ICES (formerly the Institute for Clinical Evaluative Sciences).

“More prevention of concussion is justified, not just in exuberant young athletes, but throughout the lifespan,” says Dr. Redelmeier, who is also a physician at Toronto’s Sunnybrook Health Sciences Centre and a professor of medicine at the University of Toronto.

The study adds to growing evidence linking concussions to the development of dementia. In a separate study published last year in JAMA Neurology, for example, U.S. researchers examining more than 350,000 military veterans similarly found they were two times more likely to develop dementia after experiencing a concussion.

One of the researchers of that earlier study, Kristine Yaffe, a professor of psychiatry and neurology at the University of California San Francisco, says scientists do not fully understand why concussions may lead to dementia. One possible explanation is that the injuries may accelerate brain aging and the accumulation of abnormal proteins, such as tau and amyloid, which cause damage to neurons, she says.

In the new study published on Monday, Dr. Redelmeier and his team examined data from 1993 to 2013 for nearly 29,000 Ontarians, age 65 and older, who were not previously diagnosed with dementia before suffering a concussion. They found more than 4,700 of them developed dementia over a minimum follow-up period of three years.

Patients who were prescribed a statin within 90 days of having a concussion had about a 13 per cent lower risk of dementia, compared with those who were not.

Dr. Redelmeier says patients who were on statins were taking the drugs incidentally, for reasons unrelated to their concussion, and most were taking the drug before and after their injury. The researchers found other medications, including other cardiovascular drugs and neuropsychiatric medications, did not appear to make a difference to patients’ risk of dementia.

Based on experimental models, statins can mitigate injury-related brain swelling, inflammation, and faulty microcirculation, affecting the tiniest vessels of the brain, Dr. Redelmeier says, explaining this may be why statins appear to offer some protection against dementia after a concussion.

He points out that one of the main limitations of his study is that it was not a randomized trial, so it could not show whether statins actually caused a lower dementia risk. However, he says, patients using statins tend to start off with more risk factors for dementia prior to having a concussion, so his study may, in fact, underestimate the potential benefits of the drugs.

“There may be a role for actually beginning a statin in the immediate aftermath of a concussion,” provided it is appropriate based on a patient’s age and health, Dr. Redelmeier says. But, he says, it is yet unclear how long patients would need to stay on the drug to reduce their dementia risk.

“If you’re already on a statin and unfortunate enough to have a concussion, keep taking your statin,” he advises.

More importantly, he adds, people should take precautions against brain injury: “So that means driving safely, walking mindfully, using protective gear, staying sober and staying away from risky situations.”



D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation. According to a study published in Alzheimers Association,  improvement in cerebral blood supply and microcirculation promotes remission in Alzheimer’s disease.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

Under Armour developing ‘smart’ sneaker that reads blood pressure

Under ArmourOpens a New Window. is developing a “smart” sneaker that would track the blood pressure of its wearer, according to a patent filing this week.

The sports apparel brand’s filing with the U.S. Patent and Trademark Office details two versions of a sneaker currently in development. The first version of the sneaker would link to a wearable device and transmit blood pressure that would then be used to adjust the sneaker’s fit for optimal blood flow. The second version of the sneaker contains a “blood pressure detector.”

In the patent filing, Under Armour said the sneaker is meant to help its wearer recover after a “strenuous workout.”

“There exists a need for a device and method to effectively pump blood through the plantar venous plexus and support recovery after engaging in athletic activity,” the company wrote in its filing, dated June 25.

Under Armour representatives did not immediately respond to a request for comment. Baltimore Business Journal was first to report on the filing.

The filing comes as Under Armour and other sports apparel companies seek to integrate technology into their products.

The Baltimore-based company unveiled its first smart shoe, the “HOVR Connected Series,” in 2018. The footwear line measures a runner’s gait and other workout data.


D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation. 

D’OXYVA promotes benefits related to significantly improved blood circulation, including significantly increased cardiac activity, physical fitness, metabolism, endurance, energy balance and a healthy weight by significantly improving Microcirculation that is detectable real-time with high quality diagnostics.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

The Alzheimer’s-blood pressure connection

Rock legends David Bowie and Freddie Mercury must have known something that science discovered only recently. In their rock anthem “Under Pressure,” they crooned: “Pressure pushing down on me … Chipping around, kick my brains around the floor.”

Researchers wouldn’t put it quite that way, but there is a correlation between a person’s elevated blood pressure later in life and brain health, particularly Alzheimer’s disease risk. A study in Neurology recorded the blood pressure of 1,300 people ages 59 to 102 annually for a mean of eight years. Brain autopsies of deceased subjects then revealed a link between high blood pressure and the presence of neurofibrillary tangles, characteristic of Alzheimer’s disease.

An elevated systolic, or top number, above 134 mmHG increased the odds of developing brain lesions by nearly 50%. But according to Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian, anything above 120 puts you in the “new risk zone.” The study didn’t find a correlation with an elevation of the diastolic (the bottom number) and Alzheimer’s.

The good news: Lifestyle changes can help you achieve a healthy blood pressure of around 120/75. The DASH, Mediterranean and “What to Eat When” diets are a smart starting point. Check out for info on these nutritional approaches and to download a free phone app to keep track of your numbers. Plus, ask your doc about medications and at-home, self-measured blood pressure monitors; the cuff ones are usually reliable, but should be checked against one at your doc’s office.


D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

My Neuropathy Story: This Is How My Diabetic Neuropathy Disappeared Forever

“I was first diagnosed with diabetes at a young age,” said Bryan, 50 years old. It was in his early 20s that he started to live with devastating pain in his legs from diabetic neuropathy and had deteriorating muscular degeneration. But today, Bryan can go jogging again, and even his vision is somewhat improving.


What happened?

“It’s simple, I started to look at my diet, did more research and found a new solution called D’OXYVA,” said Bryan.


Before D’OXYVA

Bryan was diagnosed with type 1 diabetes around 30 years ago. “I couldn’t believe when my doctor told me that my blood sugar levels are high,” he said, although he admitted that other risk factors were obvious, such as being overweight and the fact that diabetes runs in his family.

He ignored his diagnosis and paid little attention to diabetes. He was told to start eating healthy, yet he continued eating what he wanted and didn’t watch his weight.

“A few years ago, I started to feel tingling in my right foot, and it got worse day after day,” said Bryan. Soon, both feet felt numb and he began to feel the pain. It was so painful that he had a hard time taking a step.

At a routine checkup, his doctor wasn’t very happy with him ignoring his diabetes. His doctor told him that his blood glucose was dangerously erratic. From that time on, he became meticulous with managing his diabetes. He started using an insulin pump and other expensive technologies that he thought could help him. But despite all his efforts, Bryan’s health continued to decline, and the pain became more devastating. Despite his eye doctor’s best efforts, Bryan’s macular degeneration was not improving.


A solution called D’OXYVA

Bryan decided to do some research on his own. He remembered a patient he was sitting beside in the clinic talking about a product he had had success with. The product was called D’OXYVA.

From his research, he found out that microcirculatory dysfunction renders the diabetic foot unable to mount a vasodilatory response under conditions of stress, such as injury, and makes it functionally ischemic, even in the presence of satisfactory blood flow under normal conditions. Therefore, improving microcirculation to his feet would help with pain management and avoid further nerve damage.


D’OXYVA is noninvasive and uses an FDA-approved pharmaceutical-grade CO2. Additionally, it is a clinically validated blood flow and nerve stimulant for people suffering from neuropathy. In various clinical trials, D’OXYVA has been validated and demonstrated above-average results in improving a host of physiological functions at the same time.


It’s never too late to start a new journey

“I started off with their pro health set, and strictly followed twice a day D’OXYVA therapy as advised by their therapy expert after requesting for a customized treatment plan. They were very accommodating and professional. After 6 weeks, not only did the product help ease the pain, it got rid of the numbness. Plus, it didn’t cause side effects. My eye doctor also said he sees improvement in my vision,” said Bryan.

Now, Bryan and his wife are both in continuous D’OXYVA therapy as they found out that D’OXYVA, due to its microcirculatory enhancement capability, can help her with her varicose veins.

“I can’t wait to see how I will improve more after a few more months of using D’OXYVA,” Bryan said. He feels a new sense of vitality. He is now back on his feet, living free from the pain of diabetic neuropathy, and has better control of his blood sugar than he has ever had. He and his wife are looking forward to enjoying an active retirement full of exciting adventures and activities, including spending more time with their children and grandchildren.

“I see a new life and a new hope out there for you and for everyone who is experiencing the same,” said Bryan.


D’OXYVA® (deoxyhemoglobin vasodilator) is a novel, clinically validated blood flow and nerve stimulant for people suffering from neuropathy. In various clinical trials, D’OXYVA has validated leading independent research results and demonstrated above-average results in improving a host of physiological functions at the same time.

Subjects suffering from high blood sugar have reported neuropathy pain relief minutes after D’OXYVA was administered and long-term blood sugar level improvements in just a few weeks.

Posted on Leave a comment

Vaginal Microcirculation: Non-Invasive Anatomical Examination of the Micro-Vessel Architecture, Tortuosity and Capillary Density

To describe the vaginal microcirculatory architecture and capillary density parameters using side stream dark field imaging (SDFI), and determine feasibility and reliability of this method.
In nine healthy female volunteers SDFI measurements were performed at two different time points in the luteal phase of the menstrual cycle. Non-invasivetissue micro-angioarchitecture and vaginal capillary density measurements were assessed independently by two observers. Agreement was expressed with mean differences between the measurements of both observers and the limits of agreement. Inter- and intra-observer agreement was quantified with the intra-class  orrelation coefficient (ICC).
Vaginal microcirculatory assessment with the SDFI device was easy in use, painless and well accepted by theparticipants. Morphologically, the vaginal microcirculation revealed an array of single hairpin-shaped capillary loopsdistributed homogeneously across an imaged tissue segment. The intra-observer assessment of the capillary densitymeasurements (comparing two measurement time points of one observer) showed good agreement with an ICC ranging from 0.62 to 0.85. The inter-observer assessments of the capillary density measurements (comparing assessments of two observersaton etimepoint)revealed very good agreement, with small differences between observers and an ICC of more than 0.9.
This is the first report on both microcirculatory architecture and quantitative microcirculatory parameters of the vagina with the use of SDFI. Micro-vessels of the vagina show a recognizable pattern in our study population of young, healthy women. SDFI gives a reproducible assessment of the vaginal microcirculation offering the researcher a wide field of applications.


D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

Exploring The Link Between Inflammation And Depression: Study Suggests Women Are Affected The Most

The link between depression and the body’s inflammatory response continues getting stronger, with more research showing an ever-tighter correlation. Whether inflammation causes depression has been difficult to nail down, but findings from a new study suggest we could be getting closer to an answer. For women in particular, it seems higher levels of inflammation can lead to an underlying condition that fuels depression.

That condition is called anhedonia, defined as “a loss of enjoyment in things and activities.” Depression patients frequently experience anhedonia as a loss of positive sensation for things that used to bring joy, like visiting certain places, taking part in social activities, even eating certain foods.

Women are roughly twice as likely to be diagnosed with depression as men (about one in eight women will experience depression in their lifetimes), and anhedonia is frequently cited as a major symptom.

The study started there, trying to determine if the link between inflammation and depression plays out differently in women and men. The researchers took a more direct route than we see in most research in this area, by inducing inflammation in participants with a substance called endotoxin, which according to the study “increases inflammation in a safe, time-limited manner.” Other participants received a placebo.

Two hours later, when inflammation was peaking, the participants played a game designed to build their anticipation of a cash reward while their brains were scanned in an fMRI machine. The point of this was to evaluate activity in a brain area called the ventral striatum (VS), a core part of the brain’s dopamine-fueled “reward center.”

In the brain, anhedonia is characterized by reduced activity in the VS, which can also be described as experiencing less energy from anticipating life’s rewards (i.e. the people, places, and things that used to bring joy).

The results showed that compared to those receiving a placebo, the brains of women with the biggest inflammatory response to endotoxin also had the biggest decrease in VS activity. The same result wasn’t found in men.

“The study is the first to show that there are sex differences in neural sensitivity to reward in response to inflammation, which has important implications,” said senior author Naomi Eisenberger, PhD from the University of California, Los Angeles.  “This may suggest one reason women experience depression at a far greater rate than men, particularly for the kinds of depression that may be inflammatory in nature.”

The results are important for a few reasons. First, they further strengthen the link between inflammation and depression. Inflammation may not lurk behind all cases of depression, but at this point the evidence strongly suggests that a significant percentage of depression cases are at least influenced by inflammation. Most research in this area can’t determine the direction of the “cause arrow,” but in this study it appears increased inflammation could be causing decreased activity in the brain’s reward center.

Next, the results help fill out a growing understanding of sex differences in depression cases, pointing to a need for health professionals to pay more attention to the role inflammation could be playing especially in their female patients’ mental health.

“This [study] suggests that women with chronic inflammatory disorders may be particularly vulnerable to developing depression through decreases in sensitivity to reward,” added the study’s first author Mona Moieni, PhD, a postdoctoral researcher. “Clinicians who treat female patients with inflammatory disorders may want to pay close attention to these patients for possible onset of depressive symptoms.”

This wasn’t a huge study (115 participants) and it’ll need replication for the results to hold up, but it’s a meaningful piece in a sprawling puzzle. Next phases of the research will likely focus on why inflammation appears to influence depression differently in women and men, along with delving deeper into the link between the conditions across all patients.

The study was published in the journal Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.


The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. 

The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation.  Inflammation and the Microcirculation; by D. Neil Granger and Elena Senchenkova; San Rafael (CA): Morgan & Claypool Life Sciences; 2010.

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

Microcirculation in Hypertension, A New Target for Treatment?

The number of effective agents available for the treatment of hypertension is now substantial. However, in spite of this, most would agree that there is still considerable scope for improvement in the way hypertension is managed. In many countries, the great majority of hypertensive subjects still show imperfect blood pressure control.1 Furthermore, the reductions or improvements in end-organ damage seen during antihypertensive therapy do not always correlate well with the reduction in arterial blood pressure achieved. Thus, there seems to be a need for new therapeutic perspectives in the treatment of hypertension. One important new perspective might be provided by an enhanced appreciation of the importance of the microcirculation in the pathophysiology and treatment of hypertension.


The Microcirculation in Hypertension

In hypertension, the structure and function of the microcirculation may be altered in at least 3 ways. First, the mechanisms regulating vasomotor tone may be abnormal, leading to enhanced vasoconstriction or reduced vasodilator responses. Second, there may be anatomic alterations to the structure of individual precapillary resistance vessels, such as an increase in their wall-to-lumen ratio. Finally, there may be changes at the level of the microvascular network, perhaps involving a reduction in the density (rarefaction) of arterioles or capillaries within a given vascular bed. It is likely that the relative contributions of these factors will be different in different vascular beds and may vary between different forms and models of hypertension. Nevertheless, it is possible to discern a historical shift in the focus of antihypertensive therapy between these different mechanisms. Initially, antihypertensive therapy was directed mainly toward altering vasomotor tone and promoting vasodilation. More recently, attention was directed toward reducing or reversing changes in resistance vessel structure, and in the last few years, there has been a further evolution toward reducing or reversing microvascular network rarefaction. Interestingly, several antihypertensive agents that act acutely to reduce vasomotor tone are now known to have additional chronic actions on vessel and network structure, which may be more important in the long-term treatment of hypertension.

In this article, we review the animal and human evidence available for the role of the microcirculation during hypertension and the effects of therapy, focusing on those aspects that are likely to be common to most forms of hypertension and most organ systems.

Microcirculatory Abnormalities in Hypertension: Both Cause and Effect?

It has been known for many years that the diameter and structure of small resistance arteries can alter in response to changes in blood pressure and flow. There have been numerous reports of decreases in arteriolar diameters in experimental secondary hypertension.4 Increases in the media-to-lumen ratio of small arteries have also been widely documented in several forms of hypertension,4 consistent with the classic view that vessels maintain constant wall stress in the face of changing pressure. However, it is not clear whether similar changes occur in arterioles in primary hypertension. In SHR, arterioles have not been reported to show consistently reduced luminal diameter or wall thickening (reviewed by Struijker Boudier et al).4

A more consistent observation has been microvessel rarefaction. A reduction in the number or density of microvessels has been reported for many years in most forms of clinical and experimental hypertension. Several studies have documented microvessel rarefaction in SHR and after the experimental induction of secondary hypertension.4

It has been suggested that rarefaction may occur in 2 phases.9 The first phase of functional rarefaction involves microvessel constriction to the point of nonperfusion, possibly as a result of increased sensitivity to vasoconstrictor stimuli. The nonperfused vessels may then disappear, leading to the second phase of structural or anatomic rarefaction, which cannot be reversed by maximal vasodilation. In patients with primary hypertension, the reduction in density of capillaries in the skin of the dorsum of the fingers has recently been shown to be mainly a result of anatomic rather than functional rarefaction.10

It is therefore possible to view microvessel abnormality and rarefaction as responses to increased vascular pressure. However, this is clearly not always the case, because microvascular changes similar to those observed in hypertension can be found in conditions such as scleroderma, syndrome X, and hypertrophic cardiomyopathy in the absence of any elevation in arterial blood pressure. Furthermore, there is evidence that abnormalities in the microcirculation may cause or contribute to the elevation of blood pressure.

Targeting the Microcirculation to Prevent End-Organ Damage: Beyond Blood Pressure Reduction?

Numerous trials have demonstrated that antihypertensive therapy is effective in reducing major vascular events, including stroke and coronary heart disease. However, several forms of specific end-organ damage that primarily involve the microcirculation are thought to be secondary to hypertension, including nephropathy, retinopathy, lacunar infarction, and microvascular angina. Thus, it is to be expected that there will be additional benefits from targeting the microcirculation during antihypertensive therapy in terms of the prevention of or reduction in end-organ damage.

One of the most intensively studied forms of end-organ damage with microvascular involvement is microalbuminuria or increased urinary albumin excretion. Microalbuminuria is known to be a risk factor for cardiovascular disease and mortality in nondiabetic and diabetic individuals. In the Framingham study, proteinuria was 3 times more common in hypertensive than in normotensive individuals and was associated with a 3-fold increase in mortality.18 Importantly, hypertensive patients with microalbuminuria have an increased cardiovascular risk compared with normoalbuminuric patients with similar blood pressure.19

Although microalbuminuria may be an early marker of renal dysfunction, it is now clear that it can be reversible. A recent large-scale study of 6000 nondiabetic hypertensive patients showed that microalbuminuria can be reversed in many cases by antihypertensive therapy.20 In SHR, different antihypertensive agents have different effects on renal afferent arteriolar structure. ACE inhibition produced a greater increase in the diameters of distal afferent arterioles than a calcium antagonist of equivalent hypotensive effect.21

The heart is another organ that may suffer end-organ damage, and numerous studies have reported changes in myocardial microvessel structure and density in hypertension. During normal development, myocardial microvascular density increases during the first few postnatal weeks but then decreases, probably because angiogenesis fails to match the growth in myocyte volume.22 During the pressure-overload hypertrophy that often accompanies hypertension, the picture that emerges from studies in both animals and human patients is that microvessel growth is insufficient to prevent dilution because of the greater increase in other myocardial components; hence, microvascular density decreases.22 It has been argued that microvascular changes may make a substantial contribution to the development of cardiac failure in hypertensive patients.23

The risk of stroke is greatly increased by hypertension. Although there are multiple causes of stroke, the form that is perhaps most closely associated with small-vessel abnormality is lacunar infarction, the occurrence of small, deep infarcts thought to be caused by the occlusion or rupture of small vessels, largely as a result of hypertensive changes.

Hypertensive changes in cerebral arteriolar structure have been documented in animal models. In SHR, reductions in the external diameter and increases in the media-to-lumen ratio of cerebral arterioles have been reported.24 However, most reports conclude that neither cerebral arterioles nor capillaries undergo rarefaction in SHR or in other experimental models of hypertension. At least some forms of antihypertensive therapy can reverse structural changes in cerebral microvessels25 and can dramatically increase the lifespan of stroke-prone SHR.26,27


Abnormalities of microvessel structure and microvascular network density often accompany, and may be an important cause of, primary hypertension. Microcirculatory abnormalities are also likely to be central to many forms of hypertensive end-organ damage, including those involving the kidneys, heart, and brain. Optimal antihypertensive therapy should therefore be targeted at both large and small vessels. Available evidence suggests that the 2 longest-established classes of antihypertensive agents, diuretics and β-blockers, have no specific beneficial actions on the microcirculation. However, the results of numerous animal studies and a much smaller number of clinical studies indicate that the newer classes of antihypertensive agents and some combinations of agents offer considerable potential for improving microvessel structure and network density. It would therefore be predicted that more widespread use of these agents and combinations would enable substantial reductions in end-organ damage to be achieved, with consequent reductions in morbidity and mortality. Much further clinical research is needed to assess the extent to which this potential can be realized in clinical practice.

This article was written on behalf of the European Working Group for Microcirculation and Cardiovascular Disease. Other members are E. Agabiti-Rosei, University of Brescia, Italy; T.F. Lüscher, University Hospital, Zurich, Switzerland; G.A. MacGregor, St George’s Hospital Medical School, London, UK; and E. Vicaut, Hôpital Fernand Widal, Paris, France.


D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

Posted on Leave a comment

I started using D’OXYVA for my varicose veins, and here’s what happened in just four weeks

Annie, 35 and a mother to 3 kids, shared her story of how D’OXYVA took away her worries about the pain and appearance of varicose veins and gave her a major confidence boost in just 4 weeks.

Varicose veins have long bothersome on both sides of my family, so I was not surprised when I started to get them a little early in life,” said Annie.

Annie is an active mother and athlete. She began to notice a heaviness and pain in one of her legs long before a single varicose vein began to show up on the back of her thigh and slowly spread down her leg.

“I have always lived a healthy and active lifestyle, running and swimming being my passions, yet I still wasn’t able to escape severe vein disease. By the time I had my third child, it was painful to walk, [and even more] when I tried to continue any physical activities with my kids. The pain was unbearable,” she said.

She described how her legs looked awful, her self-confidence was disappearing, and she couldn’t wear shorts or skirts until a friend told her about D’OXYVA. She did some research and she realized that there was a safe, effective, and innovative alternative way to treat her varicose veins.

“I was a young mom with legs that looked and made me feel as though I was 100. If possible, I didn’t want to undergo any surgical procedures. After going to more than 4 vein centers and having no success using non-invasive procedures, this made me decide to try out D’OXYVA,” Annie said.

At first, she was skeptical, but to her delight, the therapy was quick, easy to use, and 100% painless.

“I requested a customized treatment plan; their customer support was so helpful and advised for me to strictly do D’OXYVA therapy once a day by directly spraying the vapor onto to the vein. I couldn’t believe my eyes; after just one 5-minute therapy session, the appearance significantly improved.”

After 4 weeks of D’OXYVA therapy, Annie is back to running better than ever and can even wear shorts without being embarrassed! She’s back on the playing field cheering on her kids, and she’s back to feeling like herself again.

“I finally have my life back and am almost completely pain free. I have such a great appreciation and admiration for everyone behind this amazing product. I have never been treated so personally and kindly by any other company offering [similar] products I have previously tried. I would recommend D’OXYVA to anyone and everyone suffering from varicose veins! The help is there; it may not be as cheap as the OTC remedies, but it’s worth it!”


D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.