Effects of Pycnogenol on Cardiac Fibrosis and Diastolic Dysfunction in Aged Hypertensive Subjects

Diastolic heart failure without left ventricular systolic dysfunction comprises 30% to 50%
of heart failure in clinical practice, and hypertensive heart disease is a major cause of
this type of heart failure. The complication of myocardial fibrosis should be avoided in
hypertensive heart disease, because increasing ventricular stiffness caused by myocardial
fibrosis leads to the development of diastolic dysfunction of the heart. Diastolic
dysfunction in patients with prolonged hypertension is often associated with myocardial
fibrosis in addition to muscular hypertrophy as a final feature of hypertensive heart
disease. The high risk of developing maladaptive cardiac remodeling during hypertension, and
failure of pharmacological treatments to limit or even reverse this progressive stiffening
of the myocardium, has led to the study of effects of Pycnogenol, a bioflavonoid-rich pine
bark extract, with pleiotropic actions on cardiovascular system. Pycnogenol prevents adverse
hypertension-induced myocardial remodeling in mice, through modulation of gene expression
and activity of enzyme matrix metalloproteinases and their tissue inhibitors, affecting
myocardial collagen degradation rate. Despite the mounting evidence suggesting the
anti-remodeling effect of Pycnogenol in animal models, the clinical efficacy of Pycnogenol
in hypertension-induced diastolic dysfunction is unreported. This leads to our central
hypothesis that Pycnogenol reverses the hypertension-induced cardiac fibrosis and diastolic
dysfunction in hypertensive patients. Therefore in this clinical investigation, we will
investigate the effects of Pycnogenol in modifying hypertension-induced cardiac fibrosis (by
measuring the serum markers of myocardial fibrosis and collagen turnover) and diastolic
dysfunction (by transthoracic echocardiogram). We expect to improve diastolic function and
ameliorate myocardial fibrosis with the nutritional supplement Pycnogenol, by modulation of
MMPs and TIMPs enzyme activities.

Inclusion Criteria:

- The subjects will consist of ambulatory males and females, 50-75 years of age, of any
race, diagnosed with hypertension (diagnosis made over 6 months), and
echocardiographic evidence of grade I or II diastolic dysfunction.

- There is no need for standardization of hypertension treatment, as we select only
patients who have diastolic dysfunction during treatment.

Exclusion Criteria:

- Unstable angina or myocardial infarction in the past 3 months.

- Biochemical evidence of renal or hepatic failure.

- Severe anemia: defined as hemoglobin level less than 7 g/dL.

- Current cancer or other major illness not associated with the heart.

- Bleeding disorders.

- Taking anticoagulants including low dose aspirin.

- Diabetes.

- Known allergy to Pycnogenol.

- Being pregnant or breastfeeding.

- Systolic blood pressure over 180 mmHg or less than 100 mmHg, and Diastolic blood
pressure over 110 mmHg or less than 50 mmHg.

- Current smoking.

- Having breast implants.

- Taking any of the following: birth control products, Diethylstilbestrol, Ephedra,
ephedrine, or pseudoephedrine (except where used in prescription products), hormone
replacement products, Isotretinoin, any product containing mercury, Phentermine in
combination with fenfluramine (including but not limited to Pondimin) or
dexfenfluramine (Redux).