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  • The prevalence of cardiovascular and metabolic diseases has


    The prevalence of cardiovascular and metabolic diseases has increased drastically over the last decades due to an overall rise in the cardiometabolic syndrome, which refers to a cadre of metabolic disorders grouped together in the forms of obesity, insulin resistance and/or type 2 diabetes mellitus, dyslipidemia and hypertension [[1], [2], [3]]. The initial definition for cardiometabolic syndrome by the World Health Organization (WHO) included impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or Calcipotriol with two or more additional components of hypertension (≥160/90 mm Hg), elevated levels of plasma triglycerides (≥150 mg/dl) and/or low levels of HDL-c (≤35 mg/dl for men and ≤39 mg/dl for women), central obesity [body mass index (BMI) ≥ 30 kg/m2 or the waist-to-hip ratio ≥ 0.90 for males and ≥0.85 for females] and/or microalbuminuria. A single (sex-specific when relevant) cut-off point was employed then for individual component although practical issues exist such as the need for a hyperinsulinemic euglycemic clamp and validation of correlation between insulin resistance and microalbuminuria. In 2001, the revised criteria by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) suggested three out of the five following indices: obesity (defined as waist circumference ≥ 102 cm in males and ≥88 cm in females [according to the 1998 National Institutes of Health (NIH) obesity clinical guidelines]), fasting glucose ≥ 110 mg/dl, hypertension (denoted as blood pressure ≥ 130/85 mm Hg based on the Joint National Committee guidelines), triglycerides ≥ 150 mg/dl and HDL-c ≤ 40 mg/dl [4]. Nonetheless, this criterion does suffer from certain limitations such as sex discrepancies in healthy HDL-c levels. The prevalence of cardiometabolic syndrome also displays sex and ethnic bias. Hispanics males display the highest prevalence at 34.76% followed by Caucasian (22.91%) and African American males (18.99%). For women, Hispanics present the highest prevalence (28.50%) followed by the African Americans (24.51%) and Caucasians (20.28%) [5]. African-Americans generally are less prone to cardiometabolic diseases compared to Caucasian although they suffer disproportionately from higher cardiovascular mortality and type 2 diabetes mellitus [6]. The greater cardiovascular risk in African Americans is most likely attributable to non-traditional cardiovascular risk factors such as C-reactive protein (CRP), homocysteine, low density lipoprotein (LDL) oxidation, lipoprotein, adiponectin, and plasminogen activator inhibitor-1 [7]. Native American Indian, Hawaiian, Polynesian and Filipino populations possess a higher risk for the cardiometabolic syndrome compared with individuals of European descent [8]. Data from the NCEP - ATP III criteria revealed a rather high variability in the prevalence in European (10 to 26%) and Indian (7.9 to 46.5%) ethnic groups [8]. However, a much lower rate was noted in Japan with a prevalence of 8.1% in men and 9.9% in women [9]. Although the syndrome as a single entity carries little clinical value itself, it does provide rationales for the recent increase in cardiovascular and metabolic diseases. Current pharmacological treatment of cardiometabolic syndrome is geared towards individual component of the syndrome including dyslipidemia, hypertension and diabetes [10]. In addition, life style modification such as regular exercise and dietary control also displayed some promises as additive measure for the clinical management of cardiometabolic syndrome [11]. A number of pathophysiological mechanisms have been postulated for cardiometabolic syndrome including inflammation, unhealthy life style, lack of physical activity, oxidative stress, mitochondrial injury, culprit genes coding syndromic or non-syndromic monogenic oligogenic or polygenic anomalies and epigenetic factors [12,13]. In addition, many inherited metabolic and endocrine disorders including glycogen storage and lysosomal disorders also participate in the pathogenesis of cardiometabolic diseases [[14], [15], [16], [17]]. These inherited metabolic and endocrine disorders may be rooted from certain inborn errors of metabolism, with characteristic childhood onset endocrine manifestations. Multiple glands may be afflicted including pancreas, thyroid and gonadal glands, leading to endocrine dysfunctions including energy disturbance in respiration, metal (hemochromatosis) and storage abnormalities (cystinosis) [18]. Recent data supported a role for autophagy dysregulation in the onset and development of cardiometabolic disease [3,[19], [20], [21]] and as well as inherited metabolic and endocrine disorders [15,[22], [23], [24]]. Although much progress has been made for the understanding of the complex etiological issues of cardiometabolic syndrome [10,12,13,25], it remains rather challenging for the optimal management of the syndrome possibly due to the multi-factorial contribution of disease pathogenesis. Here we will briefly summarize the likely contribution of various inherited metabolic and endocrine disorders to the overall prevalence of cardiometabolic disease, with a focus on autophagy.