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SHJ Vol 5, No 1                                M Ibrahim, Putting PCSK9 Inhibitors into practice
            Review Article

              The revolution in cholesterol management: putting PCSK9 Inhibitors into

                                        Mohammed Ibrahim Salih Ibrahim, MBBS, MSc
                                    Cardiologist, NMC Royal Hospital - Abu Dhabi, UAE

            Introduction                                          accelerated   atherosclerosis   and   elevated
                                                                  cardiovascular risk.
            Of an estimated 58 million deaths globally from
            all  causes  in  2005,  cardiovascular  disease       Familial  hypercholesterolemia  and  the
            (CVD)  accounted  for  30%.  This  proportion  is     lifetime burden of elevated LDL-cholesterol
            equal  to  that  due  to  infectious  diseases,
            nutritional  deficiencies,  and  maternal  and        Familial  hypercholesterolemia  is  the  most
            perinatal  conditions  combined  (1).  It  is         common  genetic  condition  known  to  medical
            important  to  recognize  that  a  substantial        science, with a population prevalence that may
            proportion  of  these  deaths  (46%)  were  of        be  as  high  as  about  1:200  (4).  Patients  with
            people  under  70  years  of  age,  in  the  more     familial  hypercholesterolemia  have  severely
            productive  period  of  life;  in  addition,  79%  of   elevated  LDL  cholesterol  levels  from  early  in
            the disease burden attributed to cardiovascular       life.  They  typically  develop  atherosclerotic
            disease is in this age group (2).                     vascular  disease  in  childhood  followed  by
                                                                  clinical coronary heart disease (CHD) by their
            One  of  the  cardiovascular  disease  (CVD)  risk    twenties         (homozygous           familial
            factors  is  atherosclerosis:  caused  when  high     hypercholesterolemia)  or  before  middle  age
            levels  of  low  density  lipoprotein  (LDL-C)  in    (heterozygous  familial  hypercholesterolemia).
            the blood build up in the inner walls of arteries,    The concept of the lifetime burden of elevated
            thickening    them     and     provoking    an        LDL  cholesterol  accounts  for  the  early
            inflammatory  response,  it  can  lead  to  heart     development  of  CHD  in  these  patients.  The
            attack or stroke. Levels of LDL-C are therefore       severity  and  duration  of  hypercholesterolemia
            often used as a surrogate marker for the risk of      act together with additional cardiovascular risk
            having a cardiovascular event (3).                    factors  such  as  other  lipid  abnormalities,
                                                                  smoking and diabetes, with a substantial risk of
            LDL-cholesterol  remains  the  key  target  of        CHD occurring once the patient has reached a
            lipid modifying therapy                               cumulative  exposure  to  160  mmol  of  LDL
                                                                  cholesterol.  Phenotypic  and/or  genotypic
            European  and  US  guidelines  continue  to           differences  between  subjects  alter  the  actual
            identify  LDL-C  as  the  main  target  for  lipid-   threshold at which any individual presents with
            modifying therapy, with the aim of improving          a high risk of CHD (4).
            long-term       cardiovascular       prognosis.
            Overwhelming  evidence,  summarized  in  these        Achieving  treatment  goals  in  patients  with
            guidelines, continues to  identify elevated  LDL      familial  hypercholesterolemia  is  challenging,
            cholesterol as a clinically important source of       even when they are diagnosed and treated. Only
                                                                  few patients with familial hypercholesterolemia
                                                                  achieve  LDL  cholesterol  goals  on  current
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