Obesity and Hypertension

 Obesity and Hypertension

The prevalence of obesity and obesity-relateddiseasesis increasing worldwide. Globally, adults with a body mass index > 25 kg/m2increased from 28.8% for men and 29.8% for women in 1980 to 36.9% for men and 38% for women in 2013.The WHO (1) and National Public Health Administrationreportshave observed a significant increasein costs forprevention and treatment of theseconditionsthus becoming also  an importantpolitical issue. Two are the most important epidemiological observations. The first, is the clear and significant increase in overweight and obesity in childhood and adolescents(boys: 12.9%. girls:13.4%). Data from the United States have reportedthat from the ’70 the childhood obesity is more thandoubled and this is particularly evident among African Americans and Hispanics .This trend has been observedalso inthe most of the European countries.Within Western Europe there is a marked variation in rates of obesity.The second aspect is the marked increaseof obesity in many developing countries due to the socioeconomic and demographic transitions. A threefold or more increase in obesity has been observed in lower socioeconomics status groups in the Middle East, Australasia and China, due to urbanization, changes in food supply and diet, and reduction in physical activity .In the last two-three decades it has been also observed a trend for an increase in the average life expectancy. While this could be considered as a good effect of “progress”, on the other side this means that the adverse metabolic effects of overweight and obesity, starting in the earlier phase of the life,will remain for a longer time period thus contributing to the increased risk of coronary heart disease, stroke, peripheral vascular diseasesand type 2 diabetes mellitus 

Several studies have shown a clear association of blood pressure increase with weight gain(7).It has been shown that obese subjects have a 3.5 fold increased likelihood of having hypertensionand that 60% of hypertension is attributable to increase in adipose stores.Data from NHANES indicate that the prevalence of hypertension among obese individuals with a BMI < 30 kg/m2 is 42.5% compared with 15.3% for lean individuals().The visceral fat distributionis in part affected by genetic factors that also contribute to the increase in blood pressure levels in obese individuals (e.g. tumor necrosis factor-, 3-adrenergic receptor, G-protein 3 subunit) (9). A Canadian study on 120 families with early onset hypertension, a total genome scan identified a cluster of overlapping quantitative trait loci on chromosome 1 for the following phenotypes: BMI, fasting insulin, leptin, diastolic blood pressure (10).Environmental factors may also be implicated in the visceral
fat distribution and increase in blood pressure values. These include alcohol intake, cigarette smoking, timing of onset of childhood obesity, changes in daily-life habits, alteration in lipid profile(11-13). All these factors associated to an impairment in insulin sensitivity, an inflammatory status and an endothelial dysfunction, may contribute to the initiation and progression of the atherosclerotic process 

Management and therapy ofobesity

 In 2012 the European Association for the Study of Obesity and the European Society of Hypertension published a statement highlighting the recommendations for preventing and treating obesity and complicated obesity based on the rationale that weight reduction may have a beneficial effect on overall risk and may contribute to blood pressure control.The first step of intervention is change in lifestyle. This non pharmacological approach is able to induce a weight loss (about 4.5 kg at 6 months) and it has been observed that each 1 kg body weight reduction, blood pressure decreases on average by 1.05/0.92 mmHg (76)but we have not to consider a linear relationship between these two reductionsand it has also to be into account thatthe compliance of the patient is the main factor to obtain a good result . 

The second step is characterized by intervention on diet regimen and use of drugs. Diet regimen should take in consideration both quality of foodsand kalories. To evaluatethe success of a diet programit has been suggested that after 6-12 weeks a 5% to 10% weight loss as compared to initial weight is reasonablebut the objective is to obtain reduction of risk factors and a BMI lower than 30 Kg/m2 

  

The third step isdrug treatment. This should be considered only associated with changes in life-style and diet program.After the negative results obtained with several drugs in the past(fenfluramine and dexfenfluramine) only few drugs are admitted for treatment: orlistat, sibutramine, rimonabant, phentermine/topiramato.Orlistat is an intestinal lipase inhibitor able to reduce body weight (2.7 kg vs placebo) with low effects of blood pressure . Sibutramine, a norepinephrine and serotonin reuptake inhibitor, induced a 4.2Kg weight loss vs placebo, but associated to intensive lifestyle changes induced a 12 kg weight loss over 1 year). The severe side effects on heart rate and blood pressure due to the norepinephrine uptake inhibition in the brain, that is a clonidine-like effect, have induced authorities to withdrawn this drugs(. Rimonabant is a cannabinoid receptor 1 antagonist capableto induce a weight loss of 5 kg vs placebo but without benefit on blood pressure and CV risk. Also this drug was withdrawn by authorities. The association of phentermine/topiramato plus diet and life-style changes has been investigated showing a weight loss of -8.1/-10.2 kg and a reduction in systolic (-6.9/-9.1 mmHg) and diastolic (-5.2/-5.8 mmHg) blood pressure with lower and higher dose respectively. No effects onoutcomes has yet been reported(). Interesting are the results obtained with liraglutide, a glucagon-like peptide (GLP)-1 agonist, at a dosage nearly twice that used in diabetic: a weight loss of 7.8 kg was associated to a reduction of 12.5 mm Hg in systolic blood pressure. This was accompanied also by an increase in heart rate of 3 bpm  

he fourth step is bariatric surgery. Usually it can be the first step in subjects with BMI higher than 45-50 kg/m2 and veryhigh CV risk. This approach demonstrated to be effective in reducing body weight and blood pressure () and is accompanied by a reduction in insulin resistance and improvement in baroreflex control. The Swedish Obese Subjects (SOS) study showed that after 11 years follow-up, patients treated with bariatric surgery maintained a reduction in body weight between 14 and 25% and benefit on mortality(HR 0.47), blood pressure and risk of diabetes  

 References 

World Health Organization. Obesity. 2008. Available at: http://www.who.int/topics/obesity/en/2.Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of high body mass index in US children  and adolescents, 2007-2008. JAMA 2010;303:242-249.3.Gakidou E, et al. Global, regional, national prevalence of overweight and obesity in children and adults 1980-2013: a systematic analysis. Lancet 2014;384:766-781.4.Ford ES, Mokdad AH. Epidemiology of obesity in the Western Hemisphere. J Clin Endocrinol Metab. 2008;93: S9-S30.5.Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel  WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 2002;162:1867-1872.6.Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mmun A, Bonneux L. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003;138:24-32.7.Wang Y, Wang QJ. The prevalence of prehypertension and hypertension among US adults according to the new Joint National Committee guidelines. Arch Intern Med 2004;164:2126-34.8.Landsberg L, Aronne LJ, Beilin LJ, Burke V, Igel LI, Lloyd-Jones D, Sowers J. Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment –A position paper of the Obesity Society and the American Society of Hypertension. Obesity 2013;21:8-24.9.Pausova Z, Jomphe M, Houde L, Vezina H, Orlov SN, Gossard F. Gaudet D, Tremblay J, Kotchen TA, Cowley AW, Bouchard G, Hamet P. Agenealogical study of essential hypertension with and without obesity in French Canadians Obes Res.2002;10:463-470.10.Hamet P, Merlo E, Seda O, Broeckel U, Tremblay J, Kaldunski M, Gaudet D, Bouchard G, Deslauriers B, Gagnon F, Antoniol G, Pausova Z, Labuda M, Jomphe M, Gossard F, Tremblay G, Kirova R, Tonellato P, Orlov SN, Pintos J, Platko J, Hudson TJ, Rioux JD, Kotchen TA, Cowley AW Jr. Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension. Am J Hum Genet.2005;76:815-822.