Weight Loss and Blood Pressure Changes, Roles Played by Genetic Susceptibility and Macronutrients.

High blood pressure (BP) affects one-third of the population in the United States. Even small increments of BP elevation are associated with increased risk of cardiovascular disease, which is a leading cause of mortality and disease burden. However, only 54% of the population with documented hypertension has their BP under control in the United States. For decades, studies have been linking heritable and modifiable risk factors and their interactions to the control of BP and the development of hypertension. Along those lines, the description of the well-designed clinical trial, the Preventing Obesity Using Novel Dietary Strategies (POUNDS) Lost trial, authored by Sun et al makes a great contribution to this issue of Hypertension. The authors found that participants with lower genetically predetermined risk of high BP had better control of their BP after a diet-induced weight loss. Hypertension is known to be a multifactorial, complex genetic disorder. With the evolution of molecular genetics, genetic susceptibility to hypertension can be quantified and serve as an estimate of lifetime risk of high BP. Over 314 genetic variants have been identified to be associated with BP levels via genome-wide association studies, with a cumulative effect of ≤10 mm Hg higher systolic BP level by 50 years of age. As the number of high BP genetic variants within an individual increases, there is a greater cumulative effect on BP levels and results in a more rapid increase in BP with aging. Although nonmodifiable, the adverse effect of a genetically predetermined risk of high BP could be partly offset by healthy lifestyles, as reported by a large observational study on over 277 000 individuals. Dietary modification is one of the most important and economical lifestyle-changing strategies to lower BP, prevent the development of hypertension, and reduce the risk of hypertension-related complications. Diet-related factors that are associated with hypertension include, but not limited to, adverse calorie balance (manifested by overweight and obesity), macroand micronutrients dietary patterns, and alcohol consumption. In terms of calorie balance, evidence from large cohort studies, such as Nurses’ Health Study and Framingham Offspring Study, suggests that obesity may be responsible for about 40% to 78% of hypertension cases. Additionally, weight loss has been shown to result in greater control of BP via mechanisms such as changes in fat distribution, activation of renin-angiotensin-aldosterone system, and activation in the sympathetic nervous system. By changing the intake of the macronutrients, including protein, fat, and carbohydrates, weight loss and optimal metabolic profiles may be achieved. The effects of macronutrients on BP have been reported in observational and randomized clinical trials, wherein most of the evidence indicates protein as being the driver of this relationship. Consistently, a greater dietary intake of protein has a BP-lowering effect in observational studies and short-term clinical trials. However, long-term, well-controlled trials are sparse on the association between macronutrients intake, such as protein, and BP control. In addition, in the few available previous studies, the macronutrient composition and dose of protein supplementation varied in a wide range (from 20 to 60 g/ day), which makes the results between studies uncomparable. Another limitation to previous studies of diet and BP is that genetic susceptibility was not taken into consideration in a comprehensive way. The original POUNDS Lost trial was designed to determine which macronutrient composition of energy-reduced diets would most benefit the overweight and obese participants with regard to weight loss and cardiovascular health during 2 years of follow-up. This study design overcame the limitation of the previous studies with a larger sample size (811 subjects enrolled), higher representation of men (40% men of the total subjects), and less loss to follow-up (80% complete the study with weight measured). Thus, comparing to other trials and observational studies, “this is thus-far the largest and the longest randomized weight-loss diet-intervention trial, allowing to examine the long-term effects of genetic effects and gene-diet interactions on BP changes,” as stated and emphasized by the authors. Before this trial, it was unclear whether a weight loss– induced reduction in BP could be partly attributed to dietary modifications or genetic susceptibility, and if so, which macronutrient composition is the most influential. Based on the POUNDS Lost trial, the authors evaluated the effect of genetic susceptibility and its interaction with macronutrient composition of the diets on BP control. Individual polygenic scores were constructed to provide a collective estimation of genetic susceptibility based on over 60 genetic variants identified from one of the largest genome-wide association studies of BP. To our knowledge, this is the first study that incorporates The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Department of Biostatistics, FMD K&L, Fort Washington, PA (Q.Z.); and Department of Epidemiology, Graduate School of Public Health, Pittsburgh, PA (I.M.). Correspondence to Iva Miljkovic, Graduate School of Public Health, A524 Crabtree Hall, 130 De Soto St, Pittsburgh, PA 15261. Email miljkovici@edc.pitt. edu Weight Loss and Blood Pressure Changes, Roles Played by Genetic Susceptibility and Macronutrients