Into the Heart

Preventing Clogged Arteries

Thrombosis is the formation or presence of a blood clot in a blood vessel (vein or artery).  The clot itself is termed a thrombus and is composed of insoluble fibrin, deposited platelets, accumulating white blood cells and entrapped red blood cells.

A thrombus (blood clot) may stay attached to the artery wall creating blockage (occlusion).
An embolus is a traveling blood clot. The blockage that is causes is called an embolism.

A micro-embolism occurs when small platelet aggregates break off from the thrombus and flow downstream, where they can occlude tiny arterioles and capillaries (micro-circulation) that deliver oxygen and nutrients to the heart and brain.

The interaction of platelets with collagen in the blood vessel wall is an originating step in platelet aggregation (build-up) leading to thrombosis.  Activated platelets release thromboxanes A2 from arachidonic acid in the phospholipids of the platelet membrane.

Platelets, platelet products, and clotting factors have causal roles in the occurrence of virtually all occlusive vascular events including heart attack and stroke.

Platelet aggregation is inhibited by cyclic AMP and by acetyl-salicylic acid (aspirin).

Incorporating eicosapentaenoic acid (EPA) in the diet reduces the frequency of thrombosis by reduction of thromboxane A2 production. (EPA) is provided in omega 3 foods such as fish oils, milled/ground flaxseed and walnuts.

Resveratrol, the polyphenolic compounds in red wine significantly inhibit platelet aggregation.

Four ounces of lowfat yogurt, sprinkled with walnuts and a tablespoon of ground flaxseed is a heart healthy breakfast. Broiled salmon with rosemary & lemon is a heart healthy dinner option. Several small servings of red wine during the week help nurtures cardiovascular health by preventing platelet aggregation .

Sources:
Alcohol, Wine and Platelet Function
JEAN-CLAUDE RUF
Biol Res 37: 209-215, 2004

The Red Wine Phenolics Trans-resveratrol and Quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease.
Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G and Goldberg DM
Clin Chim Acta  235: 207-219 (1995)

Dietary fish oils containing eicosapentaenoic acid and the prevention of atherosclerosis and thrombosis.
B J Holub
Canadian Medical Assoc Journal. 1988 September 1; 139(5): 377–381.

Estrogen Nurtures the Upper Chambers of the Heart

Atrial naturiuretic peptide is a cardiac hormone produced predominantly in the atria of the heart. Atrial natriuretic peptide induces relaxation of coronary arteries, inhibition of L-type Calcium channels* in the myocardium, suppression of the renin angiotensin system and decreased sympathetic nervous system activity. These effects are protective to the cardiovascular system and are also induced by estrogen.

The atria are the two upper chambers of the heart. Estrogen receptors are expressed in the atria. There is an increased expression and secretion of atrial natriuretic peptide in response to estrogen receptor activation.

However, during the menopausal transition and for women of postmenopausal years, diminished estrogen production can offset any of the protective regulatory mechanisms provided by artrial natriuretic peptide. For menopausal and postmenopausal women such symptoms can include heart palipitations due to altered intercellular calcium handling and hypertension due to angiotensin activity and a shift in sympathovagal balance.

*L-type calcium channels are located on vascular smooth muscle, cardiac myocytes and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into muscle cells, which in turn stimulates smooth muscle contraction (blood pressure) and cardiac myocyte contraction (heart beat).

Source:
Estrogen Receptors Activate Atrial Natriuretic Peptide in the Rat Heart
Marek Jankowski, Grazyna Rachelska
PNAS Sept 2001, Vol. 98, no 20, 11765-11770

Lowering C-Reactive Protein Levels: A Predictor of Coronary Artery Disease

Information about the inflammatory state of an individual is clinically relevant since factors that determine inflammation can be modified.

C-reactive protein (CRP) is an acute phase protein produced by the liver in response to tissue injury, inflammation, or infection. The physiological role of C-reactive protein is to direct inflammatory remnants to phagocytic cells of the lymphatic system for elimination.

Coronary Artery Disease: atherosclerosis is the process in which fatty deposits build up in the inner lining of arteries. It is considered to be a low-grade inflammatory disease.

Studies have shown that plasma levels of CRP are a strong independent predictor of endothelial dysfunction, future myocardial dysfunction, stroke, and peripheral artery disease among individuals without known cardiovascular disease.

Testing CRP levels in the blood is an additional way to assess cardiovascular disease risk.  A test called a highly sensitivity C-reactive protein (hs-CRP) assay can help determine cardiovascular disease risk.

C-Reactive Protein and Estrogen Replacement
Hormone replacement therapy for menopausal and postmenopausal women effects CRP levels. The effect of estrogen replacement on CRP is dependent on the route of administration. Studies show that transdermal estrogen replacement does not effect CRP, where oral estrogen replacement therapy increases CRP.

Transdermal estrogen replacement is not subject to first pass metabolism by the liver, this allows for  lower doses and exposes tissues to lower drug levels. Lower exposure in the liver impacts protein and lipid synthesis.

As such, in postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect. An increase in CRP levels is accompanied by a reduction in IGF-1, an anti-inflammatory growth factor.

Red Wine benefits C-Reactive Protein
Polyphenol rich red wine has pronounced anti-inflammatory effects. In particular, the resveratrol content in red wine helps inhibit tumor necrosis factor a (TNF-a) induced NF-KB activation and inflammatory gene expression and attenuates (lessens) monocyte adhesiveness to human coronary arterial endothelial cells.

At nutritionally relevant concentrations, red wine reduces the susceptibility of LDL cholesterol to (oxidation) lipid peroxidation. Oxidized LDL cholesterol is the prominent component of atheromas (fatty deposits in the arteries). Inhibiting the oxidation of LDL cholesterol blocks the initiation of a cascade of inflammatory mediators in the arterial wall causing a reduction in atherosclerotic processes. The polyphenolic compounds in red wine have antioxidant and anti-inflammatory effects which maintain lower C Reactive Protein levels and lowers the risk of cardiovascular disease.

Sources:
High Sensitivity C Reactive Protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease.
Circulation, 2001 ;103: 1813-1818.

Resveratrol attenuates TNFa induced activation of coronary arterial endothelial cells:
Role of NF-KB inibition
Anna Csiszar, Kira Smith, Nazar Labinsky
Am J Physiology Heart Circulatory Physiology 291: 1694-1699, 2006

Differential effects of oral versus transdermal estrogen replacement therapy
on C-reactive protein in postmenopausal women
Wanpen Vongpatanasin, MD, FACC Meryem Tuncel, MD, Zhongyun Wang, MD
J Am Coll Cardiol, 2003; 41:1358-1363,

Weight Gain and Menopause

Although influenced by calorie intake to a certain extent, visceral fat (belly fat) accumulation also results from estrogen deficiency due to menopause.  During the menopausal transition many women experience an imbalance of sympathetic and parasympathetic activity. Elevated sympathetic activity affects vascular and cardiac contractile function and can results in symptoms such as hot flashes and heart palpitations.

Sympathetic over stimulation and catecholamines can oppose the effects of insulin.  The role of insulin is to transport and regulate glucose. Insulin lowers blood sugar by enhancing membrane transport of glucose into muscle cells, white blood cells, and connective tissue. An absence of, insufficiency of, or decreased sensitivity of cells to insulin results in an altered pattern of glucose and fat metabolism. High insulin levels prevent the body from being able to burn or utilize body fat for energy. Fat is then stored which is recognized as weight gain.

Sources:
Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women
Kerrie L. Moreau; Kathleen M. Gavin; Angela E. Plum; Douglas R. Seals
Hypertension. 2005;45:1107.

Dysregulation of the Autonomic Nervous System Can Be a Link between
Visceral Adiposity and Insulin Resistance
Stina Lindmark, Lars Lönn, Urban Wiklund
Obesity Research 13:717-728 (2005)

Eleveated Sympathetic Activity may Promote insulin Resistance Syndrome by Activating Alpha 1 Adrenergic Receptors on Adipocytes.
McCarty MF/ Pantox Laboratories, San Diego,CA 20109

Red Wine Decreases the Initiation of Coronary Artery Disease

Inflammatory mediators have a significant role in the initiation, progression, and eventual rupture of atherosclerotic plaques.

The endothelium is a thin protective layer of cells that regulate the structure and function of the arterial wall. The adherence of monocytes to vascular endothelial cells and their migration into the the subintimal space are essential to the initiation of coronary artery disease.

Cellular adhesion molecules orchestrate the process of leukocyte rolling, adhesion and transmigration into the intima layer of the artery. Monocyte Chemoattractant Protein-1 directs monocytes into the arterial intima. Once within the intima layer of the artery monocytes differentiate into macrophages where they internalize/ingest modified lipoproteins such as oxidized LDL cholesterol. The oxidized LDL cholesterol generates a cascade of cellular events that eventually lead to plaque formation, hardening of the arteries and acute coronary events.

There are three major classes of cellular adhesion molecules: selectins, integrins and immunoglobins.
Inhibiting the direction, & adhesion of these cellular mechanism helps block the initiation of coronary artery disease.

A recent study conducted by The University of Barcelona, Spain concluded that medium level polyphenol rich red wine like Spanish sparkling wine decreased circulating biomarkers of coronary artery disease and cellular adhesion molecules such as vascular cell and intercellular adhesion molecules, E and P selectins, and monocyte chemoattractant protein-1 and CD40L. 

Previous studies have demonstrated red wines with higher levels of polyphenols such as Pinot Noir, Red Bordeaux provide cardiovascular protective effects by helping prevent the oxidation (decay) of LDL cholesterol, inhibition of platelet aggregation, and induction of nitric oxide release: vasorelaxation. 

The Barcelona study concluded that even red wines with medium level polyphenol content have a significant role in preventing the initiation and progression of coronary artery disease.

As such, light textured thin Itallian reds wine such as Bardolino or Red Lambrusco and a charming Red Beaujolais from the French country side can also protect arterial integrity and lower the risk of coronary artery disease.  Four ounces of red wine; four servings per week affords cardioprotective benefits.

Sources:
Inflammatory Markers of Atherosclerosis Are Decreased after Moderate Consumption of Cava (Sparkling Wine) in Men with Low Cardiovascular Risk
Mónica Vázquez-Agell and  Emilio Sacanella MD’s,
J. Nutr. 137:2279-2284, October 2007

Activity in Vitro of Resveratrol on Granulocyte and Monocyte Adhesion to Endothelium.
Maria E Ferrero, Albert Bertelli MD's
Am J Clin Nutr 1998;68:1204-14.