Hospital for Special Surgery researchers writing in the Journal of Clinical Investigation say that statins may be able to prevent miscarriages in women who are suffering from pregnancy complications caused by antiphospholipid syndrome (APS), according to a study in mice. In this autoimmune syndrome, the body produces antibodies directed at phospholipids, the main components of cell membranes.
In low risk pregnancies, APS is associated with a nine-fold increase in miscarriage. In high-risk pregnancies (women who have had at least three prior losses), APS is associated with a 90 percent risk of miscarriage.
"Statins may work as a treatment for women with APS-induced pregnancy complications," said Guillermina Girardi, Ph.D., associate scientist at Hospital for Special Surgery in New York, who is lead author of the study. "They are drugs that have been shown to be very safe. There are a lot of women who continue to take statins through pregnancy and the drugs have not been shown to produce birth defects." Statins do not increase the risk of bleeding like anticoagulants, the current treatment for patients with APS.
In previous studies, Dr. Girardi and colleagues showed that antiphospholipid (aPL) antibodies in female mice caused inflammation that injured the placentas and induced abortions. These antibodies activate a protein, C5a, that activates another protein, tissue factor, that is expressed on the surface of certain white blood cells called neutrophils. This spurs the neutrophils into action, they attack the placenta, and the fetus dies. While investigators had unveiled this basic chain of events, they didn't know any further details about the mechanism.
To find out, Dr. Girardi and colleagues examined the white blood cells from mice that had APS and discovered that these cells expressed certain receptors called PAR2 (protease-activated receptor 2). Stimulating this receptor led to the activation of white blood cells that attacked the placenta and hurt the fetus. Using an antibody that blocks tissue factor interaction with PAR-2, they inhibited white blood cell activation.
In another experiment, investigators tested a possible treatment. Previous studies had shown that statins, commonly used to regulate cholesterol levels, could downregulate tissue factor (diminish the number of molecules expressed on the surface of the cell). Dr. Girardi and colleagues found that statins not only downregulate tissue factor, but they also downregulate PAR-2 on white blood cells, making the cells less sensitive. So, the researchers injected statins into mice with APS and found that these drugs could prevent white blood cell activation and protect pregnancies.
Women are advised to discontinue most medications, including statins, during pregnancy, but Dr. Girardi says that no fetal defects have been reported in women who have continued to use statins while pregnant. The researchers say that careful studies should be conducted to confirm the safety of statins in pregnancy in humans. "Women that are antiphospholipid antibody positive and have a history of previous miscarriages are a good group to perform a clinical trial," Dr. Girardi said.
On average, 50 percent to 70 percent of all conceptions fail. There is an association between circulating aPL and pregnancy loss, and between 3 percent and 7 percent of pregnant women have these antibodies.
This study could also have implications for other conditions. "The study reveals a relationship between tissue factor and PAR2 in inflammation that could have implications for understanding chronic inflammatory conditions such as rheumatoid arthritis," said Dr. Girardi. Tissue factor expression on cells that line the circulatory system and certain immune cells is a characteristic feature of acute and chronic inflammation in conditions such as sepsis, atherosclerosis, Crohn's disease, and lupus. Finding a way to manipulate tissue factor and PAR2 could lead to treatments for these diseases.
Statins are a class of medications specifically prescribed to lower LDL- one of five lipid parameters of a person’s lipid profile. There are 6 available statins to choose- with three that are combination drugs that have a statin as a component of these medications. There are other classes of medications for lipid management, such as bile acid sequestrants and nicotinic acid, which is known as niacin. Yet the side effect profile is more unfavorable of these classes of medications compared with the statin class.
One’s cholesterol level is primarily due to how they produce cholesterol in their liver, which is overall genetically determined. This level is also determined by one’s lifestyle and diet as well. If a person has too much cholesterol in their blood, it can lead to hardening and narrowing of their arteries, which can lead to cardiovascular events.
To measure one’s cholesterol, a blood test called a lipid profile is obtained from a person after they have fasted for at least 12 hours. The test should also be performed only if the person is free of any acute illness, as this may affect true lipid measures. If the results prove to be abnormal, lipid lowering therapy may be initiated, according to the discretion of the person’s health care provider. This therapy usually involves a statin medication.
Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular at times that may not be necessary to control their dyslipidemia based on their lipid profile. However, since this class of drugs has existed for use for over 20 years, statins are considered safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients. Also, they have proven to reduce cardiovascular mortality with one who is treated with a statin that has dyslipidemia. In addition to lowering LDL by up to 60 percent- depending on the statin- this class of drugs also raises HDL and lowers triglycerides, which are two other lipid parameters. Both of these effects from taking a statin drug are beneficial for the patient on a statin drug for lipid management.
Statin therapy is also recommended for those patients who have a greater than twenty percent risk of developing cardiovascular disease, or those patients that have clinical evidence of this disease
Additionally, there appears to be no comparable reduction in cardiovascular morbidity or mortality, as well as a difference in the increase of one’s lifespan, if one is on any particular statin medication for their lipid management over another, others have concluded. So caution should perhaps be considered if one chooses to prescribe a statin for a patient if they are absent of, or have only mild dyslipidemia to a significant degree. Furthermore, research should be done by the health care provider if they are under the belief that one statin medication provides a greater cardiovascular benefit over another. In other words, the health care provider should be assured that any choice of statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced, and the statin selection should be determined by the results that have been shown with a particular statin.
Abstract etiologies for those who choose to prescribe statin drugs on occasion for reasons not indicated by these statin drugs- such as reducing CRP levels, or for Alzheimer’s treatment, or anything else not involved with LDL reduction with prevention if not delaying the progression of cardiovascular disease, should be thoroughly evaluated by the health care provider. As statin therapy for such patients may not be considered appropriate prophylaxis at this point for any patient who does not have the indications for which statins are approved for and treat with patients. All other benefits that appear to have favorable effects in such areas are speculative at this point due to minimal research in other areas aside from lipid management, and require further research for these disease states aside from dyslipidemia, according to many.
Statins as a particular class of drugs that seem to in fact decrease the risk of cardiovascular events significantly, it has been proven. Statins also decrease thrombus formation as well as modulate inflammatory responses (CRP) as additional benefits of the medication. For those patients with dyslipidemia who are placed on a statin, the effects of that statin on reducing a patient’s LDL level can be measured after about five weeks of therapy on a particular statin drug.
Liver Function blood tests are recommended for those patients on continued statin therapy, and most are chronically taking statins for the rest of their lives to manage their lipid profile in regards to maintaining the suitable LDL level for a particular patient presently. Patients should be made aware of potential additional side effects as well, such as muscular issues.
Yet some have said that about half of all strokes and heart attacks that do occur are not because of increased cholesterol levels of these patients. Others believe that it is oxidized cholesterol that causes vulnerable plaques to form on coronary arterial walls, which is the catalyst for a heart attack, and that there is no medicinal treatment for the formation or stabilization of these plaques to prevent heart attacks or strokes. Others who promote and support statin medicinal therapy claim that these drugs, do, in fact, stabilize these plaques, and therefore are beneficial.
As stated previously, in regards to other uses of statins besides just primarily LDL reduction, there is some evidence to suggest that statins have other benefits besides lowering LDL. These other disease states include aside from what has been stated already, those patients with dementia or Parkinson's disease, as well as those patients who may have certain types of cancer or even cataracts. Yet again, these other roles for statin therapy have only been minimally explored, comparatively speaking. Because of the limited evidence regarding additional benefits of statin medications, the drug should again be prescribed for those with dyslipidemia only at this time involving elevated LDL levels as detected in the patient’s bloodstream.
Yet overall, the existing cholesterol lowering recommendations or guidelines should possibly be re-evaluated, as they may be over-exaggerated upon tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines. This is notable if one chooses to compare these cholesterol guidelines with others in the past. The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable, unnecessary, and possibly detrimental to a patient’s health, according to others. Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality. What that ideal LDL level is may have yet to be empirically determined.
Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue. Treating children with a statin drug for dyslipidemia is controversial presently.
Dietary management should be the first consideration in regards to correcting lipid dysfunctions that may exist in patients,
Dan Abshear