ALOPECIA AND CARDIOVASCULAR RISK

ALOPECIA AND
CARDIOVASCULAR RISK
FACTORS
DR I.G AKHIONBARE

• INTRODUCTION
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• AETIOLOGY
• CARDIOVASCULAR RISK ASSESSMENT
• CONCLUSION

INTRODUCTION
• Normal human hairs can be classified according to cyclic vphases of growth. Anagen
hairs are growing hairs; catagen hairs are those undergoing transition from the
growing to the resting stage; and telogen hairs are resting hairs, which remain in the
follicles for variable periods before they fall out (teloptosis).
• Anagen hairs grow for about 3 years (1000 days), with a range between 2 and 6
years.
• Catagen hairs are in a transitional phase, lasting 1 or 2 weeks, in which all growth
activity ceases, with the eventual formation of the telogen “club” hair.
• Telogen club hairs are resting hairs, which continue in this state for 3–5 months
(~100 days) before they are released.

INTRODUCTION
• Of human hairs plucked from a normal scalp, 85–90% are anagen
hairs, and 10–15% are telogen hairs. Catagen hairs normally constitute
less than 1% of scalp hairs.
• Causes of alopecia are generally divided into the broad categories of
cicatricial and non-cicatricial alopecia.
• Often, a correct diagnosis hinges on a synthesis of clinical, histologic,
serologic, and immunofluorescent data.

INTRODUCTION
There are different types of alopecia. the main types of hair loss are:
• Alopecia Areata (AA)
• Alopecia Totalis (AT)
• Alopecia Universalis (AU)
• Alopecia Barbae
• Androgenetic Alopecia (AGA)
• Scarring Alopecias (Cicatricial Alopecias)

Androgenetic Alopecia (AGA)
• Androgenetic alopecia, or pattern alopecia, is an extremely common
disorder affecting both men and women.
• Male-pattern alopecia (common baldness) shows itself during the
teens, twenties, or early thirties with gradual loss of hair, chiefly from
the vertex and frontotemporal regions.

Androgenetic Alopecia (AGA)
• Women generally have diffuse hair loss throughout the apical scalp
with the part wider anteriorly. There is typically sparing of the frontal
hairline, although a subset of women exhibits a “male” pattern of
temporal recession.

EPIDEMIOLOGY
• Androgenetic alopecia is an extremely common disorder that affects
roughly 50% of men and perhaps as many women older than 40
years. As many as 13% of premenopausal women reportedly have
some evidence of androgenetic alopecia.
• However, the incidence of androgenetic alopecia increases greatly in
women following menopause, and, according to one author, it may
affect 75% of women older than 65 years.

EPIDEMIOLOGY
• Almost all patients with androgenetic alopecia have an onset prior to
age 40 years, although many of the patients (both male and female)
show evidence of the disorder by age 30 years.
• Anaba et al showed that the prevalence of female androgenetic
alopecia (FAGA) was 4.8% (10/207) and median age of the
participants was 59 (IQR 45,63) years

EPIDEMIOLOGY
• Olasode et al reported the overall prevalence of AGA was 29.95%,
with a gender prevalence of 24.88% and 5.06% for men and women,
respectively.
• The mean age of AGA was 51.32 ± 16.31 years, with a range of 24–90
years and male-to-female ratio of 4.9:1.

PATHOPHYSIOLOGY
• Androgenetic alopecia is a genetically determined disorder and is
progressive through the gradual conversion of terminal hairs into
indeterminate hairs and finally to vellus hairs.
• A lymphocytic microfolliculitis targeting the bulge epithelium, along
with deposits of epithelial basement membrane zone
immunoreactants, are frequently seen in androgenetic alopecia in
both sexes

PATHOPHYSIOLOGY
• Numerous studies have identified 2 major genetic risk loci for
androgenetic alopecia.
• These are the X-chromosomal AR/EDA2R locus and the PAX1/FOXA2
locus on chromosome 20. A recent genome-wide association study
compared more than 1100 severely affected cases of androgenetic
alopecia and controls to note differences in the 2 groups.

PATHOPHYSIOLOGY
• Male androgenetic alopecia has been suggested as a risk factor for severe
coronavirus disease 2019 (COVID-19) owing to the finding that males
hospitalized with COVID-19 have a high incidence of the condition.
• research indicates that infection with severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, may be
promoted by androgen signaling, which is itself essential to the etiology of

AETIOLOGY
• Androgenetic alopecia is a genetically determined condition. In 2008,
95 families were studied genetically, and the locus with strongest
evidence for linkage to androgenetic alopecia was the 3q26 site on
the X chromosome.
• Androgen is necessary for progression of androgenetic alopecia, as it
is not found in males castrated prior to puberty. The progression of
androgenetic alopecia is stopped if postpubertal males are castrated

PATHOPHYSIOLOGY
• A literature review by Kim et al indicated that patients with
androgenetic alopecia have abnormal lipid profiles, which may be a
factor in the disorder’s association with cardiovascular disease.
• In the study, significantly higher levels of serum total cholesterol,
serum triglyceride, and low-density lipoprotein cholesterol, as well as
significantly lower levels of high-density lipoprotein cholesterol, were
found in patients with androgenetic alopecia than in controls

PATHOPHYSIOLOGY
• The 5α-reduction of testosterone is increased in the scalp of balding
individuals, yielding increased dihydrotestosterone. Androgen-
inducible transforming growth factor (TGF)–β1 derived from dermal
papilla cells appears to mediate hair growth suppression.
• In congenital 5α-reductase deficiency, the type 2 isoenzyme
is lacking, and baldness does not occur.

PATHOPHYSIOLOGY
• Androgenetic alopecia is postulated to be a dominantly inherited disorder
with variable penetrance and expression.
• It has been noted that follicles from balding areas of persons with
androgenetic alopecia are able to produce terminal hairs when implanted
into immunodeficient mice.
• This suggests that systemic or external factors may play a role in

PATHOPHYSIOLOGY
• Interestingly, female androgenetic alopecia has been reported in a
patient with complete androgen insensitivity syndrome. This suggests
that factors other than direct androgen action contribute to
patterned hair loss.

CLINICAL FEATURES
• The onset of androgenetic alopecia is gradual. Men present with
gradual thinning in the temporal areas, producing a reshaping of the
anterior part of the hairline.
• For the most part, the evolution of baldness progresses according to
the Norwood/Hamilton classification of frontal and vertex thinning.
Women with androgenetic alopecia usually present with diffuse
thinning on the crown.

• The anterior hairline recedes on each side, in the Geheimratswinkeln
(“professor angles”), so that the forehead becomes high.
• Eventually, the entire top of the scalp may become devoid of hair.
Several patterns of this type of hair loss occur, but most common is
the biparietal recession with loss of hair on the vertex.

Pattern hair
loss: male, Hamilton type
III
A 46-year-old male with
bitemporal
recession of hairline and
frontal thinning of hair.

Pattern hair
loss: male,
Hamilton types
IV to V A 37-year-
old male
with loss of hair in
the frontotemporal
and vertex areas in
a
male corresponding
to Hamilton
types IV and V.

Pattern hair loss:
female, Ludwig type
II A 66-year-old
female with diffuse
thinning of hair on
the crown.

ALOPECIA AREATA
• Alopecia areata is a recurrent nonscarring type of hair loss that can
affect any hair-bearing area.
• Clinically, alopecia areata can manifest many different patterns.
Although medically benign, alopecia areata can cause tremendous
emotional and psychosocial distress in affected patients and their
families.

• Alopecia areata (in French, pelade) is characterized by rapid and
complete loss of hair in one or more round or oval patches, typically
1–5 cm in diameter, usually on the scalp, bearded area, eyebrows,
eyelashes, and less frequently, on other hairy areas of the body.
Frequency of involvement at particular sites is as follows:
• Scalp - 66.8-95%
• Beard - 28% of males
• Eyebrows - 3.8%
• Extremities - 1.3%

The condition usually is localized when it first appears, as follows:
• Single patch - 80%
• Two patches - 2.5%
• Multiple patches - 7.7%
Alopecia areata can be classified according to its pattern, as follows:
• Reticular - Hair loss is more extensive and the patches coalesce
• Ophiasis - Hair loss is localized to the sides and lower back of the scalp
• Sisaipho (ophiasis spelled backwards) - Hair loss spares the sides and back of
the head
• Alopecia totalis - 100% hair loss on the scalp
• Alopecia universalis - Complete loss of hair on all hair-bearing areas

PATHOPHYSIOLOGY
• Much evidence supports the hypothesis that alopecia areata is an autoimmune
condition.
• The process appears to be T-cell mediated, but antibodies directed to hair follicle
structures also have been found with increased frequency in alopecia areata
patients compared with control subjects
• A precipitating factor can be found in 15.1% of patients with alopecia areata.
Major life events, febrile illnesses, drugs, pregnancy, trauma, and many other
events have been reported

PATHOPHYSIOLOGY
• The outer root sheath is the structure targeted most frequently, followed by the
inner root sheath, the matrix, and the hair shaft.
• Histologically, lesional biopsy findings of alopecia areata show a perifollicular
lymphocytic infiltrate around anagen-phase hair follicles. The infiltrate consists
mostly of T-helper cells and, to a lesser extent, T-suppressor cells.
• Depletion of these T-cell subtypes results in complete or partial regrowth of hair
in the Dundee experimental bald rat (DEBR) model of alopecia areata. The
animals subsequently lose hair again once the T-cell population is replete.

PATHOPHYSIOLOGY
• The early phase of hair loss appears to be mediated by type 1
cytokines, including interleukin (IL)–2, interferon (IFN)–γ, and tumor
necrosis factor (TNF)–α.
• The frequency of positive family history for alopecia areata in affected
patients has been estimated to be 10-20% compared with 1.7% in
control subjects.

PATHOPHYSIOLOGY
• Two studies demonstrated that human leukocyte antigen DQ3
(DQB1*03) was found in more than 80% of patients with alopecia
areata, which suggests that it can be a marker for general
susceptibility to alopecia areata

PATHOPHYSIOLOGY
• Clinical evidence favoring autoimmunity
suggests that alopecia areata is associated with
other autoimmune conditions, the most
significant of which are thyroid diseases and
vitiligo.
Associated conditions may include the following:
• Atopic dermatitis
• Collagen-vascular diseases
• Down syndrome
• Psychiatric disorders - Anxiety,
personality disorders,
depression, and paranoid
disorders
• Stressful life events in the 6
months before onset

Alopecia and Cardiovascular Risk factors
• Epidemiological studies of the association between
androgenetic alopecia and cardiovascular disease have
produced varying results
• While some have shown an increase in cardiovascular risk
especially in early-onset alopecia, others have failed to
confirm this observation.

• Lesko et al showed that vertex alopecia was associated with
myocardial infarction.
• In addition, Lotufo et al showed an association between the severity
of alopecia and coronary artery disease.
• Sharma et al recruited 100 male patients from the Skin and
Venerology OPD at S. S. Hospital, Banaras Hindu University, Varanasi,
from January 2009 to June 2010 aged 25 to 40 years.

• Cases of AGA grade II or more of Hamilton and Norwood (HN) scale
were included in the study and patients suffering from CAD, telogen
effluvium, cicatricial alopecia, traction alopecia, and using any
medication for alopecia were excluded.
• In this study, FH of both AGA and CAD was significantly high. BP was
significantly high in cases as compared to controls. High BP is known
to accelerate atherosclerosis.

• There was a statistically significant difference in LDL, HDL, VLDL, and TG
of cases and controls as elevated levels of LDL are thought to be a key
determinant of CAD risk and that level of HDL is inversely related to risk.
• A significant elevation in serum lipoprotein a was found in cases as
compared to controls. Increased level of SL-a is said to be associated
with endothelial dysfunction and heart disease as it has a structure
similar to LDL but is attached to a glycoprotein called apolipoprotein-a.

Male 35 year, AGA
grade V, FH of CAD, BP
borderline, low HDL,
high TG and SH; so
predisposed to CAD

Male 36 year, AGA
grade VI, low HDL,
high LDL, VLDL, LP-
a and SH and low
SA; so at risk of
CAD

• Patients with AGA might be at an increased risk of CAD which increases with increasing
grade of AGA.
Sharma L, Dubey A, Gupta PR, Agrawal A. Androgenetic alopecia and risk of coronary artery disease. Indian Dermatol Online J. 2013;4(4):283-287. doi:10.4103/2229-
5178.120638
• In 1972 Cotton et al showed that Male Pattern Baldness and
Cardiovascular disease were closely related. Along with MPB some risk factors reported
such as hyperglycaemia, hypertension, increased BMI, and dyslipidaemia were
considered as cardiovascular risk factors
• Cotton SG, Nixon JM, Carpenter RG, et al. Factorsdiscriminating men with coronary heart disease from healthy controls. Br Heart J 1972; 34(5):458-
64.

• A study by Krishnarao et al reported that observed that baldness increased in
prevalence and severity with age. Similarly, elderly men had higher blood
pressure, DM, body weight, and cholesterol.
• They showed statistically significant association of cardiovascular
risk factors such high TG, high TC, low HDL, high LDL,high
VLDL, TC/HDL ratio of more than 5 and DM ( p < 0.05) with
vertex baldness than frontal baldness
• Krishnarao PV, Chennamasetty T,Krishnaveni A, et al. A study on association between androgenetic alopecia and cardiovascular risk factors in males with history of hair fall. J.
Evolution Med. Dent.
Sci. 2020;9(13):1054-1057, olesterol with a strong correlation with baldness

• Santiago et al reported a high frequency of metabolic syndrome
and carotid atheromatous plaques in patients with androgenetic
alopecia.

Pathogenic Mechanisms Underlying Cardiovascular
Risk In Patients With Androgenetic Alopecia
Hyperinsulinemia
• Elevated insulin levels are the main cause of metabolic syndrome and favor
intolerance to carbohydrates and central obesity
• Insulin has also been shown to favor vasoconstriction and nutritional deficiency in
the follicles of the scalp, and it enhances the effect of DHt on follicular
miniaturization.
• Satiago et el demonstrated elevated levels of insulin among patients with AGA.

Hyperaldosteronism
• Overexpression and stimulation of mineralocorticoid receptors in transgenic mice has
been shown to cause alopecia.
• Hyperaldosteronism has been posited as a cause of essential hypertension; therefore,
aldosterone would stimulate these skin
receptors, thus favoring progression of alopecia.
• Santiago et al found higher levels of aldosterone in the cases, and the difference
was statistically significant. Aldosterone values were higher only among
hypertensive cases, and that they were lower in hypertensive controls

• Androgenetic alopecia is caused by greater peripheral sensitivity to
androgens. Thus, free testosterone is converted into
DHT(dihyrotestosterone) by 5a-reductase and this leads
to follicular miniaturization.
• Similarly, 5a–reductase has been detected in blood vessels and the heart,
as have DHt receptors, which are involved in smooth muscle proliferation
in blood vessels, a key phenomenon in arteriosclerosis, together with lipid
deposition

• One of the mechanisms responsible for the increased
occurrence of atheromatous plaques could
be increased sensitivity to androgens both at the level of
the scalp—thus favoring follicular miniaturization—and
at the vascular level—thus promoting development of
atheromatous plaque.

• The association between alopecia and cardiovascular disease may have a genetic
origin. Family history plays an important role in the development of alopecia,
just as it does in cardiovascular disease.

• Chronic inflammation, which is more prevalent in patients with androgenetic
alopecia, has served to explain the association with cardiovascular disease. The
possible proinflammatory stress underlying androgenetic alopecia that manifests
with the presence of increased mean values for acute phase reactants in
individuals with alopecia could favor the increased proinflammatory cytokine
levels observed in the arterial wall and hair follicles.

Alopecia Areata And Cardiovascular Risk
Factors
• The association of androgenetic alopecia (AGA) with cardiovascular diseases
(CVDs) has been explored by several research groups.
• However, the potential for links between CVD and most other forms of hair loss
has not been actively investigated.
• Alopecia areata (AA) is an inflammatory, cell-mediated autoimmune hair loss
disease that can be associated with other inflammatory and autoimmune
diseases such as thyroiditis , and psoriasis.

Factors
• A cross sectional study by Chun Wang et al at the University of British
Columbia showed a higher plasma levels of cardiac troponin I in patients
with AA compared with controls.
• Patients with alopecia areata undergoing treatment had
lower level of cardiac troponin I
• Patient with alopecia areata plasma had high cardiac
troponin I induced apoptosis of human cardiomyocytes
• Wang, E., Santos, L., Li, X., Tran, A., Kim, S., Woo, K., … McElwee, K. (2018). Alopecia Areata is Associated with Increased Expression of Heart Disease
Biomarker Cardiac Troponin I. Acta Dermato Venereologica, 0. doi:10.2340/00015555-2964

Factors
• Kang et al showed that patients with AA were associated with a higher risk
of stroke occurrence in a 3-year follow-up period compared to controls
from a large population-based database in Taiwan.
• The cause of this association could be multifactorial and complex.
• Atopic diseases and systemic autoimmune diseases including systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease
and psoriasis were shown to be more prevalent in AA patients

Factors
• However a different statistic and finding was observed in a retrospective cohort
study that examined 1377 patients with AA and 4131 matched control subjects to
evaluate risk for AMI and ischemic stroke.
• The findings suggest that AA is protective for developing stroke and may decrease
the risk for AMI although it was not statistically significant.
• Huang, K. P., Joyce, C. J., Topaz, M., Guo, Y., & Mostaghimi, A. (2016). Cardiovascular risk in patients with alopecia areata
(AA): A propensity-matched retrospective analysis. Journal of the American Academy of Dermatology, 75(1), 151–154.
doi:10.1016/j.jaad.2016.02.1234

Factors
• Several inflammatory cytokines are involved in the cyclical hair growth. IFN-γ is
the main cytokine known to be aberrantly expressed in alopecia areata through a
CD4+ Th1 − mediated response
• It has been shown that serum levels of IFN-γ are significantly higher in patients
with alopecia totalis or alopecia universalis compared to controls
• Other cytokines elevated in AA are IL-a, IL-4, IL-2. The increased levels of these
inflammatory cytokines may be one explanation for the increased insulin
resistance in alopecia patients.

Factors
• Insulin resistance, is associated with increased hypertension and
cardiovascular disease risk. This association increases the risk of
coronary artery disease independently from the presence of other
cardiovascular risk factors such as obesity, hypertriglyceridemia,
hypercholesterolemia, a lack of physical activity, hypertension and
smoking.

CONCLUSION
• Cardiovascular disease has a major impact on morbidity
and mortality. Thus, an understanding of the relationship alopecia and
cardiovascular disease may be important in improving primary prevention.
• Cardiovascular screening by the dermatologist in patients with alopecia
could prove useful for detection of at-risk individuals and for initiation of
preventive therapy before cardiovascular disease develop

References
• Huang, K. P., Joyce, C. J., Topaz, M., Guo, Y., & Mostaghimi, A. (2016).
Cardiovascular risk in patients with alopecia areata (AA): A
propensity-matched retrospective analysis. Journal of the American
Academy of Dermatology, 75(1), 151–154.
doi:10.1016/j.jaad.2016.02.1234
• cotton Sg, nixon JM, carpenter rg, Evans DW. Factors
discriminating men with coronary heart disease from healthy
controls. Br Heart J. 1972;34:458–64
• Ellis JA, Stebbing M, Harrap SB. Male pattern baldness is not
associated with established cardiovascular risk factors in the
general population. clin Sci. 2001;100:401–4

• Lee H, Kim YC, Choi JW. Alopecia areata is not a risk factor for heart
diseases: A 10-year retrospective cohort study. PLoS One. 2021 May
7;16(5):e0250216. doi: 10.1371/journal.pone.0250216. PMID: 33961663;
PMCID: PMC8104430.
• https://emedicine.medscape.com/article/1069931-overview#a6
• Krishnarao PV, Chennamasetty T,Krishnaveni A, et al. A study on
associationbetween androgenetic alopecia andcardiovascular risk factors in
males withhistory of hair fall. J. Evolution Med. Dent.
Sci. 2020;9(13):1054-1057
• Sharma L, Dubey A, Gupta PR, Agrawal A. Androgenetic alopecia and risk of
coronary artery disease. Indian Dermatol Online J. 2013;4(4):283-287.
doi:10.4103/2229-5178.120638

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