Microvascular Disease

The Often Overlooked Reason for Poor Cardiovascular Health
By John Raimo, MS, RD
Discussions of heart disease often revolve around macrocirculation—the large coronary arteries that feed the heart. However, in many patients who complain of cardiovascular symptoms such as chest pain and who later suffer from heart attacks (myocardial infarctions), angiograms show there is no evidence of blockages in their larger arteries. In other words, many patients who were clearly having heart trouble had healthy coronary arteries. Their larger vessels showed no signs of stenosis, a term for the narrowing or blockage of arteries.

Up until about a decade ago, this was somewhat of a medical mystery. But as diagnostic tools improved, scientists began to realize that the problem with these patients occurred not in the larger coronary arteries, but rather in the smaller coronary arteries that comprise the microcirculatory system. They named this type of condition microvascular coronary disease, small vessel heart disease, or microvascular disease. Microvascular problems occur more often in women than men, but are also an important concern to males.


According to one group of researchers, “It is now accepted that the precipitation of acute coronary syndromes and, mostly, of acute myocardial infarction often occurs in patients who do not show critical stenoses [blockages]. This and other findings challenge the relevance of stenosis severity as a major pathogenetic determinant in ischemic heart disease.”1

Microcirculation supplies oxygen and nutrients to heart tissue and all of the 75 trillion cells that comprise the human body. In fact, each cell in the body has its own personal blood supply no further than 1/500th of an inch from the 18,000 miles of capillaries that comprise the microcirculatory system of the human body. Microcirculation also is important to the regulation of coronary blood flow. New techniques for exploring the coronary microcirculation have revealed that microvascular damage lowers coronary vasodilator reserve, the ability of the vessels to dilate, which is linked to an increased risk of clinical deterioration and death from heart disease.2

The characteristics of microvascular coronary disease are the same that occur in larger arteries. Atherosclerosis, the build up of plaque that blocks arteries, and endothelial dysfunction, when the vessels do not expand or dilate properly, both occur in smaller blood vessels just as they do in the larger arteries. Microvascular disease symptoms are not as obvious as the chest pain usually associated with a heart attack. Furthermore, symptoms caused by microcirculatory problems are often assumed to be caused by macrovascular issues. One more obvious sign that is associated with microvascular problems is venous insufficiency (varicose veins).

Microcirculation abnormalities often occur in subjects with high blood pressure. In fact, it is now thought that the microvascular changes that occur in hypertensive people may play a role in the end-organ damage often seen in this disease, including heart disease. In hypertension, the microvascular walls thicken and the lumen, the space within an artery, narrows, ultimately resulting in the blockage of vessels. This reduces the number of capillaries and small blood vessels known as arterioles. These destructive changes are known to occur in the microvascular system that feeds the heart muscle, the conjunctiva and retina, and the kidneys.2


TABLE 1. Possible Indications of Microvascular Dysfunction

  • Retinal Abnormalities
  • Cold hands and feet
  • Kidney Disease
  • Varicose Veins
  • Swelling of the ankles and fingers
  • Hypertension
  • Thinning of the skin and/or premature skin aging
According to one scientist, “In hypertension a vicious circle occurs, with an increase in blood pressure producing a rise in resistance in the microcirculation, leading to further elevation of blood pressure.”2 

Dysfunction in the microcirculatory system (microangiopathy) is also a significant problem in diabetics, depriving their tissues of nutrients and oxygen and decreasing the ability to remove toxins.

Clearly, microcirculation is an essential, but often poorly recognized, factor in heart health. Therefore, enhancing the microvascular system is as important as maintaining healthy cholesterol levels or tending to other aspects of cardiovascular health. Three nutrients—coenzyme Q10, the anthocyanosides found in bilberries and black currants, and nattokinase—are helpful for improving microcirculation in the body.

Coenzyme Q10

Ubiquinol, the reduced form of ubiquinone (coenzyme Q10 or CoQ10) is a potent antioxidant present in nearly all human tissues, and supplemental CoQ10 has been strongly linked to improving cardiovascular health. Numerous studies point to its beneficial effect in cardiovascular diseases.3-8

CoQ10 has been shown to enhance the efficacy of a drug in improving the forearm microcirculation of type 2 diabetics.9

Coenzyme Q10 is thought to decrease peripheral resistance, the lowering of blood flow in the small blood vessels called arterioles. When blood flow decreases, this backs up blood in the arteries that feed blood into the arteriole. Much like a 3-lane highway funneling into a single lane, there is inherent back up arising from the decreased flow capacity. The back up of blood causes the arterial pressure to increase.

Some 70-90 percent of the overall peripheral resistance of the circulatory system arises at the level of the microcirculation.2 Indeed at rest only 5 percent of the blood is in the microcirculatory system, yet upwards of 27 percent of the resistance that the heart must pump against arises in these microvessels. CoQ10’s ability to decrease peripheral resistance in hypertensive subjects, as indicated in double-blind, clinical trials, suggests it has an important influence on the microcirculation system.10 

Bilberries and Black Currants

The anthocyanosides found in bilberries and black currants can play an important role in improving the health of the body’s microcirculation. A rodent study showed that black currants can improve the function of smooth muscle in the aorta. In the animals given black currant concentrate, there occurred a relaxation of the aorta, indicating black currant improved blood flow.11


Improving the body’s microcirculation can be especially helpful for people with venous insufficiency and varicose veins. Animal studies of bilberry show that it helps decrease vascular permeability and improve vascular tone and blood flow.12

In humans, clinical trials have reached similar conclusions. One such study involved 15 patients with polyneuritis due to peripheral vascular insufficiency. Researchers gave the subjects 480 mg per day of bilberry extract and noted significant improvement in microcirculation in the subjects.13 The same dose of bilberry extract in 47 patients who suffered from venous diseases resulted in an elimination of the microstagnation that occurs in the vessels in these patients and increased blood flow in the foot.12 A review of uncontrolled trials on bilberry that involved 568 patients with venous insufficiency of the lower limbs added further support for bilberry’s vein-enhancing actions. The review found that bilberry extract rapidly decreased symptoms and improved both venous microcirculation and lymph drainage.14

Other studies have confirmed that anthocyanosides can reduce capillary fragility.15


Natto, a fermented soy cheese, contains an enzyme called nattokinase, which has been studied for its clot-dissolving abilities. In one study, 12 volunteers (six men and six women) were fed 200 grams (seven ounces) of natto. A blood sample was taken and the formation of a thrombus (clot) was then artificially stimulated. In those subjects fed natto, the time needed to completely dissolve the clot was cut in half compared to those in the control group.16-17

Clinicians have found that nattokinase affects the entire systemic circulation and will help clear blockages from tiny blood vessels as well as the larger vessels.18


Microvascular concerns may be an under-recognized reason why many individuals who experience cardiovascular symptoms have no blockages in their coronary arteries. Tending to the health of the smaller blood vessels is therefore a prudent way to ensure optimal heart health. Consuming a highly bioavailable form of coenzyme Q10 known as CoQ10-H2™ combined with nattokinase, bilberries and black currants can ensure the strength and integrity of all aspects of the vascular system.

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2. Lévy BI. [The importance of microcirculation and tissue perfusion in hypertension] [Article in French]. Curr Med Res Opin. 2005;21 Suppl 5:S1-6.

3. Belardinelli R, Mucaj A, Lacalaprice F, Solenghi M, Seddaiu G, Principi F, Tiano L, Littarru GP. Coenzyme Q10 and exercise training in chronic heart failure. European Heart Journal. 2006 Nov; 27(22): 2675-81.

4. Belardinelli R, Mucaj A, Lacalaprice F, Solenghi M, Principi F, Tiano L, Littarru GP. Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure. Biofactors. 2005: 137-45.

5. Tiano l, Belardinelli R, Carnevali P, Principi F, Seddaiu G, Littarru GP. Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischemic heart disease: a double-blind, randomized controlled study. European Heart Journal. 2007 Sept; 28(18): 2249-55.

6. Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors. 1999; 9(2-4): 273-84.

7. Langsjoen PH, Langsjoen AM, Folkers K. Long-term efficacy and safety of CoQ10 therapy for idiopathic dilated cardiomyopathy. American Journal of Cardiology. 1990 Feb; 15(65): 521-23.

8. Burke BE, Neuenschwander R, Olson RD. Randomized, double blind, placebo-controlled trial of CoQ10 in isolated systolic hypertension. Swedish Medical Journal. 2001 Nov; 94(11): 1112-17.

9. Playford DA, Watts GF, Croft KD, Burke V. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis. 2003 May;168(1):169-79.

10. McCarty MF. Coenzyme Q versus hypertension: does CoQ decrease endothelial superoxide generation? Med Hypotheses. 1999 Oct;53(4):300-4.

11. Nakamura Y, Matsumoto H, Todoki K. Endothelium-dependent vasorelaxation induced by black currant concentrate in rat thoractic aorta. Jpn J Pharmacol. 2002 May;89(1):29-35.

12. Colantuoni A, Bertuglia S, Magistretti MJ, Donato L. Effects of Vaccinium myrtillus anthocyanosides on arterial vasomotion. Arzneim Forsch. 1991;41:905-9.

13. Lietti A, Cristoni A, Picci M. Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and anti-inflammatory activity. Arzneim Forsch. 1976;26:829-832.

14. Pennarola R, et al. The therapeutic action of the anthocyanosides in microcirculatory changes due to adhesive-induced polyneuritis. Gazz Med Ital. 1980;139:485-91.

15. Mian E, Curri SB, Lietti A, Bombardelli E. Anthocyanosides and the walls of the microvessels: further aspects of the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med. 1977 Oct 31;68(52):3565-81.

16. Suzuki Y, Kondo K, Matsumoto Y, Zhao BO, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci. 2003 Jul 25;73(10):1289-98.

17. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol. 1990;84(3):139-43.

18. Mitchell Fleisher, MD., DHt., DABFM. Cardiovascular Health a Clinician’s Perspective.



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