Doctor says statin drug hypersensitivity reactions are potentially life-threatening

This paper was published in Chest 1999 Mar;115(3):886-9

Study title and authors:
Polymyalgia, hypersensitivity pneumonitis and other reactions in patients receiving HMG-CoA reductase inhibitors: a report of ten cases.

Liebhaber MI, Wright RS, Gelberg HJ, Dyer Z, Kupperman JL.
Department of Medicine and Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA. mil1258@pol.net

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10084510

 
This paper, headed by Dr Myron Liebhaber from the University of California Los Angeles School of Medicine, describes ten patients who developed hypersensitivity-type reactions after taking statin medications. (A hypersensitivity reaction is an exaggerated inflammatory response by the immune system to a drug or other foreign substance).
 
Patient 1
(i) Nine months after starting lovastatin, 20 mg daily, a 54 year old man developed urticaria over his entire body and angioedema of his upper lip. (Urticaria also known as hives, is a kind of skin rash with pale red, raised, itchy bumps. Angioedema is swelling under the skin).
(ii) Tests revealed an autoimmune disorder (where the body attacks its own tissues).
(iii) Lovastatin was discontinued, and his symptoms gradually resolved over seven days. 
 
Patient 2
(i) A 69-year-old woman was referred for medical attention for an evaluation of a cough.
(ii) She had been taking pravastatin, 20 mg to 40 mg daily, for 6 years.
(iii) She was given medication and her condition improved although tests revealed impaired lung function.
(iv) Over the next six weeks her symptoms became much worse and she was given medication.
(v) Despite the treatment her cough continued.
(vi) A scan found inflammation in the lungs.
(vii) A lung biopsy led to a diagnosis of pravastatin induced hypersensitivity pneumonitis. (Hypersensitivity pneumonitis is a disease in which your lungs become inflamed when they are exposed to substances to which you are allergic).
(viii) The pravastatin was stopped, and her cough resolved two weeks later.
(ix) A follow-up scan seven weeks after the first one showed complete resolution of the inflammation in her lungs.

Patient 3
(i) Three years after starting pravastatin 20 mg daily, a 77 year old man developed gradually increasing inflammation, with symptoms of polymyalgia. (Polymyalgia is pain, stiffness and tenderness in many muscles).
(ii) In addition, three years after starting pravastatin, the patient had retinal vein thrombosis. (Retinal vein thrombosis is when one of the tiny retinal veins becomes blocked by a blood clot).
(iii) The patient then developed a sudden worsening of his heart function.
(iv) After discontinuing the pravastatin his heart function normalized, and resolution of the polymyalgia syndrome occurred over one month.

Patient 4
(i) A 66-year-old man started taking lovastatin, 20 mg daily.
(ii) Four years later, the patient complained of fatigability, drowsiness, shortness of breath and joint pain.
(iii) Tests revealed inflammation and an autoimmune disorder.
(iv) He stopped taking lovastatin.
(v) His symptoms gradually resolved over two months.

Patient 5
(i) A 76-year-old woman  was started on lovastatin, 20 mg daily.
(ii) One year later she began to complain of muscle aches.
(iii) Two years later, she developed shortness of breath, joint pain and psoriasis. (Psoriasis is inflammation of the skin and develops as patches of red, scaly skin).
(iv) She then had a small heart attack and a failed artery graft.
(v) Lovastatin was discontinued, and she had a gradual improvement of her shortness of breath, joint pain, muscle pain and back pain over a two month period.

Patient 6
(i) An 80-year-old woman had been taking simvastatin, 10 mg daily, for 3 years.
(ii) She began having shortness of breath on exertion.
(iii) Investigations revealed she had inflammation.
(iv) Simvastatin was discontinued.
(v) Her shortness of breath improved and inflammation decreased over the next three weeks.

Patient 7
(i) A 49-year-old man had been taking pravastatin, 40 mg daily, for four years.
(ii) During this period, he had generalised itching and urticaria, along with swelling of his fingers and feet.
(iii) Test revealed an autoimmune disorder.
(iv) Pravastatin was discontinued, and the itching and swelling gradually resolved over the subsequent month.

Patient 8
(i) A 77-year-old woman was treated with pravastatin, 10 mg daily, for 3 years.
(ii) During this period, she had generalised itching with urticaria.
(iii) Investigations revealed she had inflammation and an autoimmune disorder.
(iv) Her symptoms cleared one month after discontinuing the pravastatin.

Patient 9
(i) A 53 year old man started to take pravastatin 40 mg daily.
(ii) Within six months he developed angioedema (swelling) of the eyelids and a sensation of his airway closing. 
(iii) He discontinued pravastatin.
(iv) His symptoms gradually resolved 30 days later.

Patient 10
(i) A 73-year-old man developed intense itching and urticaria after taking pravastatin 20 mg daily for three years. 
(ii) Tests revealed she had an autoimmune disorder.
(iii) He discontinued pravastatin and 12 days later his symptoms resolved.

Dr Liebhaber concluded: "We feel it is important for clinicians to recognize early symptoms of statin drug hypersensitivity because they are potentially life-threatening".

Men who develop heart disease eat less saturated fat

This study was published in the American Journal of Clinical Nutrition 1978 Jul;31(7):1270-9

 

Study title and authors:

Dietary intake and the risk of coronary heart disease in Japanese men living in Hawaii.

Yano K, Rhoads GG, Kagan A, Tillotson J.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/665576

This study investigated the relationship of dietary intakes to subsequent development of coronary heart disease. The study lasted for six years and included 7,705 men, aged 45 to 68.

Regarding saturated fat consumption, the study found:
(a) Men who died from heart disease consumed 3.1% less saturated fat compared to men who remained free from heart disease.
(b) Men who developed coronary insufficiency consumed 6.2% less saturated fat compared to men who remained free from heart disease. (Coronary insufficiency is an inadequate blood flow to the heart muscles).
(c) Men who developed angina consumed 3.1% less saturated fat compared to men who remained free from heart disease.

Link between statin use and interstitial lung disease

This paper was published in the Medical Journal of Australia 2007 Jan 15;186(2):91-4

Study title and authors:
Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease.

Walker T, McCaffery J, Steinfort C.
Geelong Hospital, Geelong, Victoria, Australia. timw@barwonhealth.org.au

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17223772

Dr Tim Walker from Geelong Hospital Australia describes seven patients who developed interstitial lung disease while on statin treatment. Interstitial lung disease refers to a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). (Interstitial pneumonitis is a type of interstitial lung disease).

Patient 1
(i) A 78 year old woman was admitted to hospital with shortness of breath and a dry cough.
(ii) She had been taking atorvastatin 10 mg per day for one year.
(iii) Investigations revealed extensive fibrous connective tissue (fibrosis) in the lungs.
(iv) Atorvastatin was withdrawn.
(v) Her lung function got slowly worse, and she still had shortness of breath at a three year check up.

Patient 2
(i) A 78 year old man sought medical attention at hospital after suffering from shortness of breath for three weeks.
(ii) He had been taking pravastatin 40 mg daily for ten years.
(iii) Investigations revealed extensive emphysema, fibrosis and impaired lung function.
(iv) He initially continued statin treatment and experienced respiratory failure necessitating home oxygen therapy before stopping statins.
(v) He died 18 months later of respiratory failure.

Patient 3
(i) A 74 year old woman was admitted to hospital with a cough and fever of three days duration, (consistent with pneumonia), and a background of worsening shortness of breath.
(ii) She had been taking simvastatin 10 mg daily for two years, then 20 mg daily for one year.
(iii) Investigations found extensive infiltration (fluid, fibrosis) of the lungs and a biopsy led to a diagnosis of interstitial pneumonitis.
(iv) Simvastatin was withdrawn.
(v) There was a gradual reduction in infiltrate, and her lung function was stable at a nine-month follow up.

Patient 4
(i) An 83 year old man arrived at hospital with shortness of breath which had worsened over a six month period.
(ii) He had been taking pravastatin for one year.
(iii) Investigations revealed he had fibrosis.
(iv) He stopped taking pravastatin.
(v) Despite withdrawl of pravastatin his condition slowly worsened.

Patient 5
(i) A 67 year old woman sought medical help after suffering with shortness of breath for nine months and a dry cough for six months.
(ii) She had been taking simvastatin for five years.
(iii) Investigations found patchy infiltration of her lungs and she had a TLCO of 22%. (TLCO is Transfer factor of the lung for carbon monoxide and is the extent to which oxygen passes from the air sacs of the lungs into the blood. A low TLCO indicates fibrosis and restrictive lung disease).
(iv) She stopped taking simvastatin.
(v) She had a marked improvement: TLCO increased to 51% after one month, and improved further to 65% after one year.

Patient 6
(i) A 68 year old man was admitted to hospital with worsening shortness of breath and hypoxia. (Hypoxia is where there is not enough oxygen getting to the tissues of the body).
(ii) He had been taking simvastatin for two years.
(iii) Investigations revealed he had inflammation and fibrosis in the lungs.
(iv) He continued to take simvastatin.
(v) He died nine months later from heart disease exacerbated by interstitial lung disease.

Patient 7
(i) A 64 year old man sought medical attention for worsening shortness of breath and a dry cough.
(ii) He had been taking atorvastatin 20 mg daily for three years, then 40 mg daily for two years.
(iii) Investigations found the patient had fibrosis. he had a TLCO of 44%.
(iv) Atorvastatin was withdrawn.
(v) He had an improvement in his condition. His TLCO increased to 52% after two months.

Dr Walker also reviewed some other adverse side effects that statins may cause.

He found:
(a) The most commonly reported adverse effects include gastrointestinal upset, headache, rash and a dose-dependent elevation in levels of liver transaminases (enzymes).
(b) The most potentially serious, adverse effects include myopathy (muscle disease) and polyneuropathy (life threatening neurological disorder that occurs when many nerves throughout the body malfunction simultaneously).
(c) Statins have been associated with lung diseases, lupus-like syndromes and muscle and skin inflammation diseases.
(d) Many patients take statin therapy for many months or years before these symptoms develop.
(e) Their clinical features vary in severity from mild dry cough and rash through to severe and progressive respiratory failure.

Dr Walker concluded: "We hope that our description of our patients and review of the possible role of statins in interstitial lung disease will raise awareness of the potential association between statin therapy and this uncommon and often fatal condition".

Higher consumption of saturated fat and cholesterol associated with a lower risk of Parkinsons Disease

This study was published in Neurology 2005 Jun 28;64(12):2040-5

 

Study title and authors:

Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study.

de Lau LM, Bornebroek M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM.

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15985568

This study investigated the association of fat intake with the risk of Parkinson disease. The study lasted for six years and included 5,289 subjects, (aged 55 years and over), who were free of dementia and Parkinsons at the start of the study.

The study found:
(a) For every 13.2 grams daily increase in fat consumption there was a 31% decreased risk of Parkinsons Disease.
(b) For every 7.2 grams daily increase in saturated fat consumption there was a 18% decreased risk of Parkinsons Disease.
(c) For every 60 mg daily increase in cholesterol consumption there was a 19% decreased risk of Parkinsons Disease.

A higher consumption of saturated fat and cholesterol is associated with a lower risk of Parkinsons Disease.

Cholestatic jaundice induced by atorvastatin

This paper was published in the Israel Medical Association Journal 2009 Jul;11(7):440-1

Study title and authors:
Cholestatic jaundice induced by atorvastatin: a possible association with antimitochondrial antibodies.

Minha S, Golzman G, Adar I, Rapoport M.
Department of Internal Medicine C, Assaf Harofeh Medical Center, Zerifin, Israel. Minha.saar@gmail.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19911499

This paper describes the case of a man who developed cholestatic jaundice while taking atorvastatin. (Cholestatic jaundice is when the normal flow of bile from the liver to the small intestine is interupted).

(i) A 68 year old man was admitted to hospital complaining of fever, dark urine and hives (itchy rash).
(ii) He was taking atorvastatin 20 mg per day.
(iii) Physical examination revealed he had jaundice and large areas of hives.
(iv) Abnormal laboratory results included elevated liver function tests with a cholestatic pattern:
total bilirubin 7.4 mg/dl (normal 0.2–1.0 mg/dl)
alkaline phosphatase 555 U/L (normal 39–117 U/L)
alanine aminotransferase 250 U/L (normal 4–41 U/L)
aspartate aminotransferase 50 U/L (normal 5–38 U/L)
lactate dehydrogenase 540 U/L (normal 240–480 U/L)
(v) A diagnosis of drug-induced liver damage was made.
(vi) The patient stopped taking atorvastatin and he had a rapid biochemical and clinical improvement.
(vii) During the following four weeks the patient was discharged and readmitted twice with a similar clinical and laboratory findings.
(viii) A liver biopsy revealed on his next admission revealed severe inflammation.
(ix) Further investigation revealed that between admissions and prior to each recurrent bout of cholestatic hepatitis the patient had renewed his treatment with atorvastatin.  
(x) Complete cessation of atorvastatin was followed by a return to normal values of liver function tests and a complete clinical recovery.

High fat diets boost calcium absorption

This study was published in the American Journal of Clinical Nutrition 2000 Aug;72(2):466-71

 

Study title and authors:

Factors associated with calcium absorption efficiency in pre- and perimenopausal women.

Wolf RL, Cauley JA, Baker CE, Ferrell RE, Charron M, Caggiula AW, Salamone LM, Heaney RP, Kuller LH.

Departments of Epidemiology, Education, and Genetics, University of Pittsburgh, USA. wolf@exchange.tc.columbia.edu

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10919942

 
Wolf notes that low calcium is linked to high blood pressure, colorectal cancer, bone loss and the risk of osteoporosis.

The purpose of this study was to examine factors that affect the efficiency of calcium absorption in women. The study included 142 healthy pre- and perimenopausal women, aged 46-54 years, (93.7% were premenopausal).

The study found:
(a) Women who consumed the most fat, absorbed calcium more efficiently than women who consumed the least fat.
(b) Women who consumed the least fibre, absorbed calcium more efficiently than women who consumed the most fibre.
(c) Women who consumed diets with the lowest ratio of fat to fibre had 19% lower calcium absorption values than did women who consumed diets with the highest ratio of fat relative to fibre.
(d) Women who had the highest vitamin D levels, absorbed calcium more efficiently than women with the lowest vitamin D levels. (Vitamin D is only found in food of animal origin such as lard, fish, butter and egg yolks).

The results of the study show that a high-fat diet helps women to efficiently absorb calcium.

Statin use linked to musculoskeletal diseases, joint pain and injuries

This study was published in the Journal of the American Medical Association Internal Medicine 2013:1-9

Study title and authors:
Statins and Musculoskeletal Conditions, Arthropathies, and Injuries
Ishak Mansi, MD; Christopher R. Frei, PharmD, MSc; Mary Jo Pugh, PhD; Una Makris, MD; Eric M. Mortensen, MD, MSc

This study can be accessed at: http://archinte.jamanetwork.com/article.aspx?articleid=1691918

The objective of the study was to determine whether statin use is associated with musculoskeletal disorders. ( Musculoskeletal disorders can affect the body's muscles, joints, tendons, ligaments and nerves). This analysis compared 6,967 statin users with 6,967 nonusers.

The study found:
(a) Statin users had a 19% increased risk of all musculoskeletal diseases compared to nonusers.
(b) Statin users had a 13% increased risk of injury-related diseases (dislocation, sprain, strain) compared to nonusers.
(c) Statin users had a 9% increased risk of drug-associated musculoskeletal pain compared to nonusers.
(d) Statin users had a 7% increased risk of joint pain compared to nonusers.

Mansi concludes: "Musculoskeletal conditions, arthropathies, injuries, and pain are more common among statin users than among similar nonusers".

Polyunsaturated fat associated with bone mineral loss whereas saturated fat may offer protection

This study was published in the American Journal of Clinical Nutrition 2004 Jan;79(1):155-65

 

Study title and authors:

Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids.

Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM.

Department of Medicine and Therapeutics, University of Aberdeen, United Kingdom. h.macdonald@abdn.ac.uk

 

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/14684412

The menopausal transition is characterised by rapid bone loss. The objective of the study was to ascertain which dietary factors influence skeletal loss around the time of the menopause. In the study, the bone mineral density was measured at the start of the study and five years later in 891 women initially aged 45-55.

Regarding fat intake, the study found:
(a) A higher intake of saturated fat was correlated with a protective effect from bone mineral loss.
(b) A higher intake of polyunsaturated fat was correlated with lower bone mineral density

Long-term statin treatment may be associated with chronic peripheral neuropathy

This paper was published in the European Journal of Clinical Pharmacology 1999 Jan;54(11):835-8

 

Study title and authors:

Statins and peripheral neuropathy.

Jeppesen U, Gaist D, Smith T, Sindrup SH.

Department of Neurology, Odense University Hospital, Denmark.

 

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/10027656

This paper reports of seven cases of peripheral neuropathy associated with long-term statin therapy.

(i) Diagnosis of neuropathy by statin therapy was confirmed after all other causes of neuropathy were thoroughly excluded.
(ii) Neuropathy symptoms manifested up to seven years after initiation of statin therapy.
(iii) In all seven cases the neuropathy affected the nerve fibres and with affection of both thick and thin nerve fibers.
(iv) The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to one year in four cases after statin treatment had been withdrawn.

Jeppesen concluded: "Long-term statin treatment may be associated with chronic peripheral neuropathy".