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Vitamin D pearls
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Case: A 56-year-old man with a history of type 2 diabetes, hypertension, hyperlipidemia, and obesity calls clinic to discuss concerns about COVID-19, stating: “I want to do everything I can to reduce my risk of infection.” In addition to physical distancing, mask wearing, hand hygiene, and control of chronic conditions, which of the following supplements would you recommend for this patient?
1. Coenzyme Q10 160 mg twice a day
2. Vitamin D 2,000 IU daily
3. Vitamin E 400 IU daily
4. Vitamin B12 1,000 mcg daily
Of these choices, vitamin D supplementation is likely the best option, based on the limited data that is available.
Risk factors for worse COVID-19 outcome, such as older age, obesity, and more pigmented skin are also risk factors for vitamin D deficiency. This makes the study of vitamin D and COVID-19 both challenging and relevant.
In a recent study of 7,807 people living in Israel, Merzon and colleagues found that low plasma vitamin D level was an independent risk factor for COVID-19 infection. Mean plasma vitamin D level was significantly lower among those who tested positive for COVID-19 (19.00 ng/mL) than negative (20.55 ng/ mL). After controlling for demographic variables and several medical conditions, the adjusted odds ratio of COVID-19 infection in those with lower vitamin D was 1.45 (95% confidence interval, 1.08-1.95; P < .001). However, the odds of hospitalization for COVID-19 was not significantly associated with vitamin D level.1
Prior studies have also looked at vitamin D and respiratory infection. Martineau and colleagues analyzed 25 randomized, controlled trials with a pooled number of 11,321 individuals, including healthy ones and those with comorbidities, and found that oral vitamin D supplementation in daily or weekly doses had a protective effect against acute respiratory infection (adjusted odds ratio, 0.88; 95% CI, 0.81-0.96; P < .001). Patients with vitamin D deficiency (less than 25 nmol/L) experienced the most protective benefit. Vitamin D did not influence respiratory infection outcome.2
These studies suggest an adequate vitamin D level may be protective against infection with COVID-19, but who will benefit from vitamin D supplementation, and in what dose? Per U.S. Preventive Services Task Force guidelines, there is insufficient evidence to recommend screening for vitamin D deficiency in asymptomatic adults. Regarding daily dietary intake, the Institute of Medicine recommends 600 IU for persons aged 1-70, and 800 IU for those aged over 70 years. Salmon (447 IU per 3 oz serving), tuna (154 IU), and fortified milk (116 IU) are among the most vitamin D–rich foods.3 The recommended upper level of intake is 4,000 IU/day.
Too much of a good thing?
Extra vitamin D is stored in adipose tissue. If it builds up over time, storage sites may be overwhelmed, causing a rise in serum D level. While one might expect a subsequent rise in calcium levels, studies have shown this happens inconsistently, and at very high vitamin D levels, over 120 ng/mL.4 Most people would have to take at least 50,000 IU daily for several months to see an effect. The main adverse outcome of vitamin D toxicity is kidney stones, mediated by increased calcium in the blood and urine.
Several animal models have demonstrated hypervitaminosis D–induced aortic and coronary artery calcification. Like with kidney stones, the mechanism appears to be through increased calcium and phosphate levels. Shroff and colleagues studied serum vitamin D levels and vascular disease in children with renal disease on dialysis and found a U-shaped distribution: Children with both low and high vitamin D levels had significantly increased carotid artery intima-media thickness and calcification.5 Given the specialized nature of this population, it’s unclear whether these results can be generalized to most people. More studies are warranted on this topic.
Other benefits
Vitamin D is perhaps most famous for helping to build strong bones. Avenell and colleagues performed a Cochrane meta-analysis of vitamin D supplementation in older adults and found that vitamin D alone did not significantly reduce the risk of hip or other new fracture. Vitamin D plus calcium supplementation did reduce the risk of hip fracture (nine trials, pooled number of individuals was 49,853; relative risk, 0.84; P = .01).6
A lesser-known benefit of vitamin D is muscle protection. A prospective study out of the Jewish Hospital of Cincinnati followed 146 adults who were intolerant to two or more statins because of muscle side effects and found to have a vitamin D level below 32 ng per mL. Subjects were given vitamin D replacement (50,000 units weekly) and followed for 2 years. On statin rechallenge, 88-95% tolerated a statin with vitamin D levels 53-55 ng/mL.7
Pearl
Vitamin D supplementation may protect against COVID-19 infection and has very low chance of harm at daily doses at or below 4,000 IU. Other benefits of taking vitamin D include bone protection and reduction in statin-induced myopathy. The main adverse effect is kidney stones.
Ms. Sharninghausen is a medical student at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].
References
1. Merzon E et al. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: An Israeli population‐based study. FEBS J. 2020. doi: 10.1111/febs.15495.
2. Martineau AR et al. Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583
3. “How to Get More Vitamin D From Your Food,” Cleveland Clinic. 2019 Oct 23. https://health.clevelandclinic.org/how-to-get-more-vitamin-d-from-your-food/.
4. Galior K et al. Development of vitamin d toxicity from overcorrection of vitamin D Deficiency: A review of case reports. Nutrients. 2018;10(8):953. doi: 10.3390/nu10080953
5. Shroff R et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):1239-46. doi: 10.1681/ASN.2007090993.
6. Avenell A et al. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Syst Rev. 2014 Apr 14;2014(4):CD000227. doi: 10.1002/14651858.CD000227.pub4.
7. Khayznikov M et al. Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. N Am J Med Sci. 2015;7(3):86-93. doi:10.4103/1947-2714.153919
Is carpal tunnel syndrome the tip of the iceberg?
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
Sinus headaches
A 29-year-old woman presents for evaluation. She reports that she has had frequent headaches over the past 12 months that include pressure pain on her forehead, under her eyes, and over her cheeks. She usually has nasal congestion as well. She has not had any fevers or purulent nasal discharge. What is the most likely diagnosis?
A. Cluster headaches.
B. Migraine headaches.
C. Sinus headaches.
D. Tension headaches.
Myth: Recurrent sinus headaches are common.
Most physicians and patients would diagnose this case as sinus headache, but it is actually a common variant of migraine headache. Sinus headaches are rare, and when they do occur, they are almost always in the setting of acute sinusitis. Recurring headaches are rarely due to sinus problems.
In regard to sinus headache, the International Headache Society (IHS) classification states that chronic sinusitis is not a cause of headache and facial pain unless it relapses into an acute sinusitis (Expert Rev. Neurother. 2009;9:439-44). The recurrent nature of the headaches in this patient suggests a primary headache disorder, with migraine being the most likely.
In a study of 2,991 patients with self-diagnosed or physician-diagnosed “sinus headaches,” 88% of the patients met IHS criteria for migraine (Arch. Intern. Med. 2004;164:1769-72). In this study, most of the patients had symptoms suggesting sinus problems, with the most common symptoms being sinus pressure (84%), sinus pain (82%), and nasal congestion (63%).
The likely cause for these symptoms in migraine patients is vasodilation of the nasal mucosa that can be part of the migraine event (Expert Rev. Neurother. 2009;9:439-44).
In the Sinus, Allergy and Migraine Study, 100 patients who believed they had sinus headaches were recruited. All of the patients received a detailed history and physical exam, and all received a headache diagnosis based on IHS criteria (Headache 2007;47:213-24).
Final diagnoses were as follows: Migraine with or without aura, 52%; probable migraine, 23%; chronic migraine with medication overuse headache, 11%; nonclassifiable headache, 9%. A total of 76% of migraine patients reported pain in the distribution of the second division of the trigeminal nerve, and 62% experienced bilateral forehead and maxillary pain with their headaches.
It is interesting that both these studies showed the same thing: More than 85% of patients who think they have sinus headache actually meet criteria for migraine headache.
Two other articles also give strong evidence that patients with recurrent “sinus” headaches have causes other than sinus disease as the cause.
Dr. Mustafa Kaymakci and his colleagues studied 98 patients who had headaches diagnosed as “sinus” headaches (J. Int. Med. Res. 2013;41:218-23). All patients received a detailed history and physical, nasal endoscopy, and sinus CT scans. All patients who did not have findings that could be considered the cause of the headaches were diagnosed according to IHS criteria.
A total of 61 (62%) were diagnosed with migraine headache, 26 (27%) diagnosed with tension-type headache, and 11 (11%) had cluster headache. Seventy-seven percent of these patients had previously received at least one treatment for sinusitis.
Another study, by Dr. Mohsen Foroughipour and his colleagues, gave similar results (Eur. Arch. Otorhinolaryngol. 2011;268:1593-6). In this study, 58 patients with “sinus” headache were evaluated, with final diagnosis of migraine in 40 patients (69%), tension-type headache in 16 patients (27%), and chronic sinusitis with recurrent acute episodes in 2 patients (3%). Recurrent antibiotic therapy was given to 73% of the tension-type headache patients and 66% of the migraine patients.
In a study by Dr. Elina Kari and her colleagues, patients who had a history of “sinus headaches” were treated as though all these headaches were migraines (Laryngoscope 2008;118:2235-9). Fifty-four patients were enrolled, and 38 patients completed the study. All patients had nasal endoscopy and sinus CT scans that were negative. They were then given migraine-directed treatment to use for their headaches.
The majority of the patients who dropped out of the study did so because they did not believe their headaches could be due to migraines, and they did not want to take the migraine medications.
Of the 38 patient who completed the study, 31 patients (82%) had a significant reduction of headache pain with triptan use, and 35 patients (92%) had a significant response to migraine-directed therapy.
These studies show us that recurrent “sinus headaches” are unlikely to be due to sinus disease. More likely, they represent migraine headache or, less likely, tension headache or cluster headache. Evaluation should include categorizing the headache by clinical features (IHS criteria) to make a diagnosis, followed by a trial of appropriate treatment for headache type. In patients who don’t meet criteria for a specific headache type, a trial of migraine-directed therapy is reasonable.
Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington Medical School. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
A 29-year-old woman presents for evaluation. She reports that she has had frequent headaches over the past 12 months that include pressure pain on her forehead, under her eyes, and over her cheeks. She usually has nasal congestion as well. She has not had any fevers or purulent nasal discharge. What is the most likely diagnosis?
A. Cluster headaches.
B. Migraine headaches.
C. Sinus headaches.
D. Tension headaches.
Myth: Recurrent sinus headaches are common.
Most physicians and patients would diagnose this case as sinus headache, but it is actually a common variant of migraine headache. Sinus headaches are rare, and when they do occur, they are almost always in the setting of acute sinusitis. Recurring headaches are rarely due to sinus problems.
In regard to sinus headache, the International Headache Society (IHS) classification states that chronic sinusitis is not a cause of headache and facial pain unless it relapses into an acute sinusitis (Expert Rev. Neurother. 2009;9:439-44). The recurrent nature of the headaches in this patient suggests a primary headache disorder, with migraine being the most likely.
In a study of 2,991 patients with self-diagnosed or physician-diagnosed “sinus headaches,” 88% of the patients met IHS criteria for migraine (Arch. Intern. Med. 2004;164:1769-72). In this study, most of the patients had symptoms suggesting sinus problems, with the most common symptoms being sinus pressure (84%), sinus pain (82%), and nasal congestion (63%).
The likely cause for these symptoms in migraine patients is vasodilation of the nasal mucosa that can be part of the migraine event (Expert Rev. Neurother. 2009;9:439-44).
In the Sinus, Allergy and Migraine Study, 100 patients who believed they had sinus headaches were recruited. All of the patients received a detailed history and physical exam, and all received a headache diagnosis based on IHS criteria (Headache 2007;47:213-24).
Final diagnoses were as follows: Migraine with or without aura, 52%; probable migraine, 23%; chronic migraine with medication overuse headache, 11%; nonclassifiable headache, 9%. A total of 76% of migraine patients reported pain in the distribution of the second division of the trigeminal nerve, and 62% experienced bilateral forehead and maxillary pain with their headaches.
It is interesting that both these studies showed the same thing: More than 85% of patients who think they have sinus headache actually meet criteria for migraine headache.
Two other articles also give strong evidence that patients with recurrent “sinus” headaches have causes other than sinus disease as the cause.
Dr. Mustafa Kaymakci and his colleagues studied 98 patients who had headaches diagnosed as “sinus” headaches (J. Int. Med. Res. 2013;41:218-23). All patients received a detailed history and physical, nasal endoscopy, and sinus CT scans. All patients who did not have findings that could be considered the cause of the headaches were diagnosed according to IHS criteria.
A total of 61 (62%) were diagnosed with migraine headache, 26 (27%) diagnosed with tension-type headache, and 11 (11%) had cluster headache. Seventy-seven percent of these patients had previously received at least one treatment for sinusitis.
Another study, by Dr. Mohsen Foroughipour and his colleagues, gave similar results (Eur. Arch. Otorhinolaryngol. 2011;268:1593-6). In this study, 58 patients with “sinus” headache were evaluated, with final diagnosis of migraine in 40 patients (69%), tension-type headache in 16 patients (27%), and chronic sinusitis with recurrent acute episodes in 2 patients (3%). Recurrent antibiotic therapy was given to 73% of the tension-type headache patients and 66% of the migraine patients.
In a study by Dr. Elina Kari and her colleagues, patients who had a history of “sinus headaches” were treated as though all these headaches were migraines (Laryngoscope 2008;118:2235-9). Fifty-four patients were enrolled, and 38 patients completed the study. All patients had nasal endoscopy and sinus CT scans that were negative. They were then given migraine-directed treatment to use for their headaches.
The majority of the patients who dropped out of the study did so because they did not believe their headaches could be due to migraines, and they did not want to take the migraine medications.
Of the 38 patient who completed the study, 31 patients (82%) had a significant reduction of headache pain with triptan use, and 35 patients (92%) had a significant response to migraine-directed therapy.
These studies show us that recurrent “sinus headaches” are unlikely to be due to sinus disease. More likely, they represent migraine headache or, less likely, tension headache or cluster headache. Evaluation should include categorizing the headache by clinical features (IHS criteria) to make a diagnosis, followed by a trial of appropriate treatment for headache type. In patients who don’t meet criteria for a specific headache type, a trial of migraine-directed therapy is reasonable.
Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington Medical School. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
A 29-year-old woman presents for evaluation. She reports that she has had frequent headaches over the past 12 months that include pressure pain on her forehead, under her eyes, and over her cheeks. She usually has nasal congestion as well. She has not had any fevers or purulent nasal discharge. What is the most likely diagnosis?
A. Cluster headaches.
B. Migraine headaches.
C. Sinus headaches.
D. Tension headaches.
Myth: Recurrent sinus headaches are common.
Most physicians and patients would diagnose this case as sinus headache, but it is actually a common variant of migraine headache. Sinus headaches are rare, and when they do occur, they are almost always in the setting of acute sinusitis. Recurring headaches are rarely due to sinus problems.
In regard to sinus headache, the International Headache Society (IHS) classification states that chronic sinusitis is not a cause of headache and facial pain unless it relapses into an acute sinusitis (Expert Rev. Neurother. 2009;9:439-44). The recurrent nature of the headaches in this patient suggests a primary headache disorder, with migraine being the most likely.
In a study of 2,991 patients with self-diagnosed or physician-diagnosed “sinus headaches,” 88% of the patients met IHS criteria for migraine (Arch. Intern. Med. 2004;164:1769-72). In this study, most of the patients had symptoms suggesting sinus problems, with the most common symptoms being sinus pressure (84%), sinus pain (82%), and nasal congestion (63%).
The likely cause for these symptoms in migraine patients is vasodilation of the nasal mucosa that can be part of the migraine event (Expert Rev. Neurother. 2009;9:439-44).
In the Sinus, Allergy and Migraine Study, 100 patients who believed they had sinus headaches were recruited. All of the patients received a detailed history and physical exam, and all received a headache diagnosis based on IHS criteria (Headache 2007;47:213-24).
Final diagnoses were as follows: Migraine with or without aura, 52%; probable migraine, 23%; chronic migraine with medication overuse headache, 11%; nonclassifiable headache, 9%. A total of 76% of migraine patients reported pain in the distribution of the second division of the trigeminal nerve, and 62% experienced bilateral forehead and maxillary pain with their headaches.
It is interesting that both these studies showed the same thing: More than 85% of patients who think they have sinus headache actually meet criteria for migraine headache.
Two other articles also give strong evidence that patients with recurrent “sinus” headaches have causes other than sinus disease as the cause.
Dr. Mustafa Kaymakci and his colleagues studied 98 patients who had headaches diagnosed as “sinus” headaches (J. Int. Med. Res. 2013;41:218-23). All patients received a detailed history and physical, nasal endoscopy, and sinus CT scans. All patients who did not have findings that could be considered the cause of the headaches were diagnosed according to IHS criteria.
A total of 61 (62%) were diagnosed with migraine headache, 26 (27%) diagnosed with tension-type headache, and 11 (11%) had cluster headache. Seventy-seven percent of these patients had previously received at least one treatment for sinusitis.
Another study, by Dr. Mohsen Foroughipour and his colleagues, gave similar results (Eur. Arch. Otorhinolaryngol. 2011;268:1593-6). In this study, 58 patients with “sinus” headache were evaluated, with final diagnosis of migraine in 40 patients (69%), tension-type headache in 16 patients (27%), and chronic sinusitis with recurrent acute episodes in 2 patients (3%). Recurrent antibiotic therapy was given to 73% of the tension-type headache patients and 66% of the migraine patients.
In a study by Dr. Elina Kari and her colleagues, patients who had a history of “sinus headaches” were treated as though all these headaches were migraines (Laryngoscope 2008;118:2235-9). Fifty-four patients were enrolled, and 38 patients completed the study. All patients had nasal endoscopy and sinus CT scans that were negative. They were then given migraine-directed treatment to use for their headaches.
The majority of the patients who dropped out of the study did so because they did not believe their headaches could be due to migraines, and they did not want to take the migraine medications.
Of the 38 patient who completed the study, 31 patients (82%) had a significant reduction of headache pain with triptan use, and 35 patients (92%) had a significant response to migraine-directed therapy.
These studies show us that recurrent “sinus headaches” are unlikely to be due to sinus disease. More likely, they represent migraine headache or, less likely, tension headache or cluster headache. Evaluation should include categorizing the headache by clinical features (IHS criteria) to make a diagnosis, followed by a trial of appropriate treatment for headache type. In patients who don’t meet criteria for a specific headache type, a trial of migraine-directed therapy is reasonable.
Dr. Paauw is a professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington Medical School. He is the Rathmann Family Foundation Chair in Patient-Centered Clinical Education. Contact Dr. Paauw at [email protected].
